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ASSOCIATION OF BODY MASS INDEX, SAGITTAL ABDOMINAL DIAMETER AND WAIST-HIP RATIO WITH CARDIOMETABOLIC RISK FACTORS AND ADIPOCYTOKINES IN ARAB CHILDREN AND ADOLESCENTS
Center of Excellence in Biotechnology, King Saud University, Saudi Arabia
Objective: Sagittal abdominal diameter (SAD) is a novel anthropometric measure hypothesized to be a surrogate measure of visceral abdominal obesity in adults. This study aims to determine whether SAD is superior to other anthropometric measures such as body mass index (BMI) and waist to hip ratio (WHR) in terms of association to cardiometabolic risk and circulating adipocytokine concentrations in a cohort of Saudi children and adolescents. Methods: A total of 948 (495 boys and 453 girls) apparently healthy children with varying BMI, aged 10-17 years, were included in this cross sectional study. Fasting glucose, lipid profile, leptin, adiponectin, resistin, insulin, TNF-α and aPAI-1 were measured in serum and HOMA-IR was calculated. MetS components were defined according to the International Diabetes Federation (IDF) criteria. Results: BMI was superior to SAD as well as WHR, and had the highest number of significant associations to MetS components and adipocytokines even after adjustment for age and gender, including blood pressure, lipids, glucose and leptin. Conclusion: In conclusion, while SAD is significantly associated with components of MetS among children and adolescents, it is not superior to BMI. The use of SAD therefore may not be practical for use in the pediatric clinical setting. Follow-up studies are needed to determine whether SAD has clinical significance in terms of harder outcomes such as predicting diabetes mellitus or cardiovascular diseases.
VITAMIN D SUPPLEMENTATION AS AN ADJUVANT THERAPY FOR PATIENTS WITH T2DM: AN 18-MONTH PROSPECTIVE INTERVENTIONAL STUDY
Center of Excellence in Biotechnology, King Saud University, Saudi Arabia
Background: Vitamin D deficiency has been associated with impaired human insulin action, suggesting a role in the pathogenesis of diabetes mellitus type 2 (T2DM). In this prospective interventional study we investigated the effects of vitamin D3 supplementation on the metabolic profiles of Saudi T2DM subjects pre- and post-vitamin D supplementation over an 18-month period. Methods: T2DM Saudi subjects (men, N=34: Age: 56.6 ± 8.7 yr, BMI, 29.1 ± 3.3kg/m2; women, N=58: Age: 51.2 ± 10.6 yr, BMI 34.3 ± 4.9 kg/m2;) were recruited and given 2000 IU vitamin D3 daily for 18 months. Anthropometrics and fasting blood were collected (0, 6, 12, 18 months) to monitor serum 25-hydroxyvitamin D using specific ELISA, and to determine metabolic profiles by standard methods. Results: In all subjects there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (32.2±1.5nmol/L) to 18 months (54.7±1.5nmol/L; p<0.001), as well as serum calcium (baseline=2.3±0.23mmol/L vs. 18 months=2.6±0.1mmol/L; p=0.003). A significant decrease in LDL- (baseline=4.4±0.8mmol/L vs. 18 months=3.6±0.8mmol/L, p<0.001] and total cholesterol (baseline=5.4±0.2mmol/L vs. 18 months=4.9±0.3mmol/L, p<0.001) were noted, as well as a significant improvement in HOMA-β function (p=0.002). Majority of the improvements elicited were more prominent in women than men. Conclusion: In the Saudi T2DM population receiving oral Vitamin D3 supplementation (2000 IU/day), circulating 25-hydroxyvitamin D levels remained below normal 18 months after the onset of treatment. Yet, this “suboptimal” supplementation significantly improved lipid profile with a favorable change in HDL/LDL ratio, and HOMA-β function, which were more pronounced in T2DM females.
TEA AND COFFEE CONSUMPTION IN RELATION TO VITAMIN D AND CALCIUM LEVELS IN SAUDI ADOLESCENTS
Center of Excellence in Biotechnology, King Saud University, Saudi Arabia
Background: Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents. Methods: A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays. Results: Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9-12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure. Conclusion: This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively.
PREVALENCES OF OVERWEIGHT, OBESITY, HYPERGLYCAEMIA, HYPERTENSION AND DYSLIPIDAEMIA IN THE CO-OPERATION COUNCIL OF THE ARAB STATES OF THE GULF (GCC): SYSTEMATIC REVIEW
, A. MCKay, A. Majeed, A. Balasanthiran
Imperial College London, United Kingdom
Objectives: To examine the prevalence of risk factors for diabetes and its complications in the Co-operation Council of the Arab States of the Gulf (GCC) region. Design: Systematic review. Setting: GCC states (United Arab Emirates, Bahrain, Saudi Arabia, Oman, Qatar, Kuwait). Main outcome measures: Prevalences of overweight, obesity and hyperglycaemia, hypertension and hyperlipidaemia. Results: 45 studies were included in the review. Reported prevalences of overweight and obesity in adults were 25 – 50 % and 13 – 50 %, respectively. Prevalence appeared higher in females and to hold a non-linear association with age. Current prevalence of impaired glucose tolerance was estimated to be 10 – 20 %. Prevalence appears to have been increasing in recent years. Estimated prevalences of hypertension and dyslipidaemia were few and used varied definitions of abnormality, making review difficult, but these also appeared to be high and increasing. Conclusions: There are high prevalences of risk factors for diabetes and diabetic complications in the GCC region, indicative that their current management is suboptimal. Enhanced management will be critical if escalation of diabetes-related problems is to be averted as industrialization, urbanisation and changing population demographics continue.
GREEN TEA EXTRACTS AMELIORATE DIABETIC COMPLICATIONS IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
M. Ali, M.M. Thomson, K.K. Al-Qattan, H.I. Nazar, D.J. JS
Department of Biological Sciences, Kuwait University, Kuwait
Diabetes is a chronic metabolic disorder characterized by deficient insulin secretion associated with chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. Various studies have shown that in type-1 and type-2 diabetes, there is increased oxidative stress resulting in increased formation of free radicals and decreased antioxidant potential. In the present study, STZ-induced diabetic rats drank 0.1% green tea extract for 8 weeks. Our results showed significant changes
in all disturbances in biochemical and physiological parameters in green tea-treated STZ-induced diabetic rats compared to non-treated diabetic rats. Significant changes included reduction of blood sugar, cholesterol and triglycerides, increase in serum insulin and decrease in glycated hemoglobin. Kidney function was also significantly improved. An increase in antioxidant activity and decrease in free radical production was observed. A marked increase in weight gain was seen in the rats drinking green tea compared to the diabetic control rats. In addition, drinking green tea extract alleviated diabetic nephropathy and hypertension. Our findings strongly support the premise that regular consumption of green tea extract not only prevents diabetes but might also be useful in slowing the progression of diabetes.
CASE CONTROL STUDY OF THE EFFECT OF A NUTRITIONAL STRATEGY CALLED «GOURMET NUTRITION» ON THE COMPLIANCE TO CARDIOVASCULAR LIFESTYLES RECOMMENDATIONS
1 , F. Paillard 2 , T. Coutureau 3
Study Objectives: To evaluate the impact of a global dietetic approach on the evolution of clinical, biological parameters and quality of life(QOL) of patients and their compliance to the cardiovascular lifestyles recommendations (CVLR) provided by their practitioners. Methods: randomized case-control study in overweight patient presenting at least one risk factor of the metabolic syndrome. Intervention group (IG) benefited from the global dietetic approach provided by Seb combining NutriCook, Actifry, VitaCuisine, education for their use, access to recipes and Internet service . The control group (CG) received only the usual advises of the practitioner. Evaluation criteria were waist circumference (WS), a clinico-biological score involving morphologic, lipidic and HBP parameters, a score of alimentary vascular protection (QAC) and the SF12 QOL. Results: 62 patients in the IG and 65 in the CG. 37.8% are overweight, 62.2% are obese.. After 3 months, results show a decrease of 1.7 points of the waist circumference in IG vs 0.1cm in CG, a greater improvement of the clinico-biological score, (0.4 vs -0.2, p<0.05), of the QAC score (1.7 vs -0.3, p<0.05) and of the sub score « fruit and vegetable ». The QOL is improved in IG group and decreased in CG and especially for “well being perception” (2.8 vs -3.3, p=0.0518), « vitality » (9.2 vs 1.2, p=0.0568) and «social management» (6.0 vs -2.4, p=0.0554).
Chaire d’Evaluation des Allégations de Santé Ceren ESC Dijon, France; 2 Service de Cardiologie CHU de Pontchaillou Rennes, France; 3 Groupe SEB, Selongey, France
Conclusion: The global dietetic approach called “gourmet nutrition” influences the clinical outcomes of overweight and obese patients, through a re-enforcement of the medical practitioners‟ recommendations.
EVOLUTION OF CARDIOVASCULAR LIFESTYLE BEHAVIOURS OCCURRING IN HYPERCHOLESTEROLEMIC PATIENTS CONCOMITANTLY TO THE INTAKE OF PHYTOSTEROL-SUPPLEMENTED YOGHURT
1 , J. Chapman 1 , L. Masana 3 , O. Descamps 4 , E. Bosi 5 , E. Bruckert 1
Emmas ESC centre Hospitalier Universitaire, Dijon, France; 2 Hôpital Pitié Salpêtrière, Paris, France; 3 Saint Joan University, Reus, Spain; 4 Polyclinique du Centre Hospitalier de Jolimont, Haine-Saint-Paul, Belgium; 5 Ospedale San Raffaele, Milano, Italy
Objective: to assess the evolution of cardiovascular lifestyle behaviours in hypercholesterolemic patients occurring concomitantly with changes in their daily intake of phytosterol-supplemented yoghurt (Phyto-SY). Methods: Nationwide prospective observational study conducted in Spanish and French general practice Each GP proposed lifestyle modification to 5 consecutive patients presenting with hypercholesterolemia, (taking or not hypocholesterolemic drugs) and recommended daily consumption of Phyto-SY. Study design included an inclusion visit, a patient‟s self-monitoring assessment after 1 month and a final end-visit after four months. Main evaluation criterion: nutritional lifestyle score. Secondary criteria: Total, LDL and HDL cholesterol, waist circumference, daily walking time. Results: 2376 hypercholesterolemic patients, 56.2 years old ± 11.9 (women 54.8%) were included. Nutritional lifestyle score decreased from 15.4 ± 5.4 to 8.7± 4.0 (p<0,0001), either in never-treated patients (15.3 ± 5.4 to 8.6 ± 3.9; p<0,0001) or in patients treated with hypocholesterolemic drugs (15.5 ± 5.4 to 8.9 ± 4.1 ; p<0,0001). Total cholesterol decreased 8.0% (<0.0001), HDL-C increased 6.0% (<0.0001), and LDL-C decreased 9.5% (<0.0001). Frequency of walking (>30 min) increased from 59.3% to 78.3% (p<0.0001); by contrast overweight frequency decreased from 22.8% to 17.5% (p<0.0001) and waist circumference from 94.6 ± 13.3 cm to 93.0 ± 12.8 (p<0.0001). Conclusion: Improvement in nutritional lifestyle score, involving regular consumption of Phyto-SY over 4 months was significantly linked to a healthier lifestyle and to beneficial modification of atherogenic lipid profile, thereby reflecting patient empowerment in a “real life” context.
EARLY MARKERS OF ATHEROGENESIS AND RENAL DYSFUNCTION ARE IDENTIFIED IN EARLY STAGES OF ABNORMAL GLUCOSE METABOLISM
1 , F.F. Ribeiro-Filho 2 , P.A. Lotufo 3 , I. Bensenor 3 , S.R.G. Ferreira 1
1 School of Public Health, University of São Paulo, Brazil; 2 Medicine Department, Federal University of Para, Brazil; 3 Medicine Department, University of São Paulo, Brazil
Background: Abnormal glucose metabolism, preceding overt diabetes, is associated with increased cardiovascular risk. Whether early markers of atherogenesis and renal dysfunction could be identified in this condition is unclear. Objective: To examine non-traditional cardiometabolic risk factors in individuals stratified by glycemic status. Methods: 998 adults without diabetes or cardiovascular disease were classified as normoglycemic or dysglycemic (fasting plasma glucose ≥100mg/dL and HbA1c ≥6% or 2h-glucose ≥140mg/dL). Anthropometry, inflammatory markers, E-selectin and cystatin-C concentrations were compared. Results: 33.8% had dysglycemia; mean values (SD) of BMI [27.1(4.2) vs. 26.0(4.0) kg/m2, p,0.001], abdominal circumference [89.9(11.5) vs. 85.0(11.0) cm, p<0.001], E-selectin [93.7(65.0) vs. 82.3(53.2) ng/mL, p=0.004] and cystatin-C [0.85(0.61) vs. 0.68(0.60) mg/L, p=0.001], but not inflammatory markers - IL-6 [19.8(44.1) vs. 18.6(35.1) pg/mL, p=0.622] and TNF-α [29.0(139.8) vs. 24.0(99.6)pg/mL, p=0.520] - were higher in dysglycemic than in the normoglycemic group respectively. E-selectin but not cystatin-C was associated with BMI (r=0.133, p=0.009) and abdominal circumference (r=0.143, p=0.005) in the dysglycemic group. Conclusions: Besides adiposity, dysglycemia was also associated with higher E-selectin concentration, which could favor molecules adhesion to endothelium. Association between anthropometry and E-selectin supports that adiposity contributes to the initial atherogenic process. Lack of association of anthropometry with cystatin-C – an early marker of renal dysfunction – might suggest a glucose-dependent renal damage. The deleterious role of impaired glucose metabolism on cardiovascular and renal risk profile can be disclosed assessing early markers, as circulating E-selectin and cystatin-C. This hypothesis needs to be tested in prospective studies.
LIPID AND LIPOPROTEIN PROFILES AFTER 14 WEEKS OF ELECTRICAL STIMULATION IN RECENT SPINAL CORD INJURED MEN
1 , S. Ceruelo-Abajo 2 , J.A. Godino-Durán 2 , F. Navarro-Valdivielso 1 , J. Florensa-Vila 2
Faculty of Sport Science, Toledo, Spain, 2 Hospital Nacional de Parapléjicos, Toledo, Spain
Objective: The aim of the present study was to investigate the effect of 14 weeks of electromyostimulation training on blood lipid and lipoprotein profiles in recent spinal cord injured men. Materials/Methods: Five recent spinal cord injured men received
14 weeks of surface electromyostimulation on the quadriceps femoris muscle, while 3 other men served as controls. Blood samples were drawn at fasting conditions before and after 14-wk intervention. Total cholesterol (TC) was assayed enzymatically (LX20 PRO Beckman Coulter, Diamond Diagnostics, USA). High density lipoprotein (HDL-C) was assayed following elimination of other particles and reaction with cholesterol esterase (LX20 PRO Beckman Coulter, Diamond Diagnostics, USA). Low density lipoprotein (LDL-C) was estimated using the Friedewald equation. Plasma triglyceride was measured enzymatically (LX20 PRO Beckman Coulter, Diamond Diagnostics, USA). The TC/HDL-C and LDL-C/HDL-C ratios were calculated. Wilcoxon and Mann-Whitney U test were used (SPSS for Windows, v. 17.0, Inc., Chicago, IL). A level of P<0.05 was accepted as significant. Results: LDL-C, ratio TC/HDL-C and ratio LDL-C/HSL-C were different between groups before the training. In the intervention group, all markers decreased after the 14 weeks of electromyostimulation; however, only the 14,8% decrease in total cholesterol was significant. In the control group, changes were not statistically significant. Conclusion: Although a positive trend was observed in both groups, it could be concluded that lipid and lipoprotein profiles are minimally affected by electromyostimulation in recent spinal cord injured men. Further studies are warranted, including diet control, to maximize the benefits of physical interventions on lipid and lipoprotein profiles.
PRELIMINARY RESULTS OF GLUCOSE METABOLISM AFTER 14 WEEKS OF ELECTROMYOSTIMULATION IN RECENT SPINAL CORD INJURED MEN
1 , S. Ceruelo-Abajo 2 , M.S. Diaz-Merino, J.A. Godino-Durán 2 , F. Navarro-Valdivielso 1 , J. Florensa-Vila 2
Faculty of Sport Science, Toledo, Spain, 2 Hospital Nacional de Parapléjicos, Toledo, Spain
Objective: The aim of the present study was to investigate the effect of 14 weeks of electromyostimulation training on glucose metabolism in recent spinal cord injured men. Materials/Methods: Five recent spinal cord injured men received 14 weeks of surface electromyostimulation on the quadriceps femoris (QF) muscle, while 2 other men served as controls. A standard oral glucose tolerance test (OGTT) was performed before and after the 14-wk training. Blood samples were drawn at fasting and up to 120min later following OGTT with 30min intervals. Glucose was assayed by glucose oxidase (LX20 PRO Beckman Coulter, Diamond Diagnostics, USA). Insulin and c-peptide were measured by electrochemiluminescence using the E 170 module for MODULAR ANALYTICS (Roche Diagnostics, S.L., Madrid, Spain). QF cross sectional area (CSA) was measured by magnetic resonance imaging (Siemens Magntom Trio TimTM, 3 Tesla). Changes on variables were studied using Wilcoxon or Friedman Test (SPSS for Windows, v. 16.0, Inc., Chicago, IL). A level of P<0.05 was accepted as significant. Results: Before training, blood glucose was significantly higher at 60min and 90min compared to 0min. After the 14-wk electromyostimulation training, that difference shifted to the 30min and 60min samples. For insulin and c-peptide, differences from basal concentrations moved backward from 90min at pre-trainings to 60min at post-trainings. CSA was significantly increase by 10% after electromyostimulation, while controls showed a non-significant -14% change. Conclusion: Since skeletal muscle has a remarkable role in blood glucose transport, increases in muscle mass following electromyostimulation might have induced improvements in whole body insulin-induced glucose uptake.
LONG-TERM EFFICACY OF DAPAGLIFLOZIN AS ADD-ON TO METFORMIN (MET) IN T2DM INADEQUATELY CONTROLLED WITH MET ALONE
1 , J.L. Gross 2 , D. Hennicken 3 , N. Iqbal 4 , T.A. Mansfield 4 , J.F. List 4
Aston University, Birmingham, United Kingdom; 2 Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3 Bristol Myers Squibb, Braine l'Alleud, Belgium; 4 Bristol Myers Squibb, Princeton, New Jersey, United States of America
Dapagliflozin (DAPA), a selective SGLT2 inhibitor, reduces hyperglycaemia in an insulin-independent manner by increasing renal glucose elimination. Short-term (Week 24) treatment effects were previously reported for this randomised, double-blind, placebo (PBO)- controlled trial (NCT00528879) of DAPA add-on to metformin (MET) in T2DM inadequately controlled with MET (N=546). Here, we report long-term results (Week 102). Patients 18–77y, HbA1c 7–10%, received DAPA 2.5, 5, 10mg/day or PBO, plus open-label MET (≥1500mg/day). Week 102 exploratory endpoints included changes from baseline in HbA1c, FPG and body weight (BW). 71.2% of patients completed the study. At Week 102, HbA1c (mean baseline: 8.06%) was reduced for all DAPA groups (-0.48 to -0.78%) compared with PBO (+0.02%). All DAPA groups showed greater mean reductions in FPG (-19.3 to -26.5mg/dL) compared with PBO (-10.4mg/dL). More patients achieved HbA1c<7% on DAPA (20.7–31.5%) than on PBO (15.4%). Mean BW (kg) was reduced for all DAPA groups (-2.2 to -3.4) compared with PBO (-0.7). Adverse events (AEs), serious AEs and AEs causing discontinuation were similar across groups. Events suggestive of genital infection (GenInf) were reported in 11.7–14.6% (DAPA) and 5.1% (PBO) of patients, with one discontinuation due to GenInf. Events suggestive of urinary tract infection (UTI) were reported in 8.0–13.3% (DAPA) and 8.0% (PBO), with one discontinuation due to UTI. No event of pyelonephritis was reported. In summary, compared with PBO, DAPA added to MET over 102 weeks showed greater and sustained improvements in glycaemic control, clinically meaningful BW reduction, and no increased risk of hypoglycaemia.
LIRAGLUTIDE+METFORMIN IN T2D: CLINICAL BENEFITS WITH EARLY USE OF LIRAGLUTIDE AND SWITCH FROM SU
1 , J. Seufert 2 , A.B. Thomsen 3 , T.M. Jensen 3 , D. D'Alessio 4
Swansea University and Abertawe Bro Morgannwg University NHS Trust; 2 University Hospital of Freiburg, Freiburg, Germany; 3 Novo Nordisk A/S, Soeborg, Denmark; 4 University of Cincinnati, Cincinnati VA Medical Center, Cincinnati, Ohio, United States of America
Objective: No consensus exists for advancing treatment after first-line metformin fails. This post-hoc analysis compared clinical benefits associated with add-on liraglutide to failed metformin monotherapy (metformin-add-on; n=532) vs. sulphonylurea (SU) substitution with liraglutide in failed metformin+SU combination therapy (metformin-SU-switch; n=285). Methods: Data are from a clinical trial in which metformin monotherapy or metformin+SU (SU dose: ≤50% of maximum approved dose) was changed to metformin+liraglutide 1.8 mg. Results: Diabetes duration was longer in the metformin-SU-switch group. After 12 weeks, greater weight loss occurred in the metformin-SU-switch group (p=0.019). HbA1c reduction (-1.3% from 8.0% baseline vs. -0.6% from 7.7% baseline; p<0.0001), HbA1c target value (<7.0%) attainment (69.7% vs. 44.6% of patients; p<0.0001), and fasting plasma glucose reduction (-2.2 vs. -0.8) were greater in the metformin-add-on group than in the metformin-SU-switch group, respectively. There was also a greater fasting plasma glucose reduction in the metformin-add-on group than in the metformin-SU-switch group (-2.2 vs. -0.8, respectively). Conclusion: SU termination with switch to liraglutide may be beneficial for weight reduction. While standard clinical practice of liraglutide add-on to metformin achieves greater HbA1c reductions in a bigger proportion of patients, switching from metformin-SU to metformin-liraglutide may still prove superior for certain patients. However, these data
suggest that liraglutide may provide greater clinical benefit for glycaemic control when adding liraglutide to metformin early in disease stage instead of switching patients later in the disease stage.
EFFECTS OF AN ENERGY-RESTRICTIVE DIET WITH OR WITHOUT EXERCISE ON THE METABOLIC SYNDROME IN PATIENTS WITH ABDOMINAL OBESITY
1 , O. Belyaeva 1 , O. Berkovich 1 , E. Baranova 1 , E. Shlyakhto 2
Saint Petersburg State Medical University n. a. I.P. Pavlov, Russia; 2 Federal Center of Heart, Blood and Endocrinology n. a. V.A. Almazov Saint Petersburg, Russian Federation
Objective: to compare effects of diet and combination of diet and physical training on preventing or treatment of the metabolic syndrome (MS) features in patients with abdominal obesity (AO). Method: A 3-year randomized lifestyle intervention trial performed in 153 patients with AO, age 43,2±0,8 yrs, BMI 32,1±1,9 kg/m2. 74 patients (group 1) keep hypocaloric diet, 79 patients (group 2) keep diet and aerobic exercise. Dynamics of waist circumference (WC), the levels of BP, glucose, HDL-cholesterol, TG were measured. Results: 100% patients with AO had some metabolic disorders and 38% had MS before the treatment. In 3 year WC significantly decreased in 53 (71,6%) and 58 (73,4%) patients from 1 and 2 groups respectively (p<0,05). The occurrence of patients with low HDL-C and other components of MS was lesser in gr.2, than gr.1 (p<0,05). The dynamics of the MS in gr.1 and gr.2 after the treatment was follow: new cases appeared in 3,2% and 10% patients (p<0,05), continued in 40,9% and 5,6% patients (p<0,05), didn‟t registered in patients who had it before in 59,1% and 94,4% patients respectively (p<0,001). At the end of study MS had 18,9% and 8,6% patients gr.1 and gr.2 respectively (p>0,05). The odds ratio for MS in patients gr.1 was OR= 10,8 (4,1-28,1) and gr.2 - OR=26,5 (8,4-82,7) relatively patients who didn‟t loss weight. Conclusion: The combination of diet and physical training is more effective way for preventing or treatment of the metabolic syndrome in patients with abdominal obesity.
200 U/ML INSULIN DEGLUDEC HAS SIMILAR EFFICACY AND SAFETY TO 100 U/ML INSULIN GLARGINE IN PEOPLE WITH TYPE 2 DIABETES
1 , A. Bhargava 2 , R. Jain 3 , A. Rana 4 , H. Mersebach 4 , S.C.L. Gough 5
IDC Park Nicollet, Minneapolis, United States of America; 2 Iowa Diabetes and Endocrinology Research Center, Des Moines, United States of America; 3 Aurora Advanced Healthcare, Milwaukee, United States of America; 4 Novo Nordisk A/S, Søborg, Denmark; 5 University of Oxford, Oxford, United Kingdom
This 26-week, open-label, treat-to-target trial compared the efficacy and safety of insulin degludec (IDeg) U200 with insulin glargine (IGlar) 100 U/mL. Insulin-naïve patients with type 2 diabetes (T2D) (n=457; 57.5 years old, BMI 32.4 kg/m<2>, HbA1c 8.3%, and fasting plasma glucose [FPG] 9.6 mmol/L) were randomised to IDeg U200 or IGlar, both given once daily +metformin ±DPP-4 inhibitor. Basal insulin was titrated to a FPG target of 4-5 mmol/L. At 26 weeks, IDeg U200 effectively reduced HbA1c by 1.30%-points and was non-inferior to IGlar (estimated treatment difference [ETD] IDeg-IGlar: 0.04%-points [95%CI: –0.11; 0.19]). FPG reductions were significantly greater with IDeg U200 than with IGlar (–3.7 vs. –3.4 mmol/L; ETD: –0.42 [–0.82; –0.06], p=0.02). Rates of overall confirmed hypoglycaemia (PG<3.1 mmol/L or requiring assistance) were numerically lower with IDeg U200 vs IGlar (1.22 and 1.42 episodes/patient-year, respectively; estimated rate ratio (ERR) IDeg/IGlar: 0.86 [95%CI: 0.58; 1.28], p=0.46). Rates of nocturnal confirmed hypoglycaemia (00:01-05:59 hours) were numerically lower with IDeg (0.18 vs 0.28 episodes/patient-year, respectively; ERR: 0.64 [95%CI: 0.30; 1.37], p=0.25). Health status was assessed using the SF36.v2 questionnaire; 2 of 8 domains significantly favoured IDeg U200, including less bodily pain (ETD: 1.6 [95%CI: 0.1; 3.2], p=0.04) and improved vitality (ETD: 1.5 [95%CI: 0.1; 3.0], p=0.04). Mean daily basal insulin dose was similar (IDeg U200, 0.62; IGlar, 0.66 U/kg). In insulin-naïve patients with T2D, insulin degludec U200 improved glycaemic control similar to IGlar with a low risk of hypoglycaemia and significantly improved health status, assessed by the SF36 questionnaire.
HYPOGLYCAEMIA EVENT RATES IN TYPE 2 DIABETES PATIENTS TREATED WITH INSULIN GLARGINE PLUS METFORMIN & SULPHONYLUREA
1 , L. Meneghini 2 , A.H. Barnett 3 , T. Reid 4 , M.P. Dain 5 , W. Landgraf 6 , A. Vlajnic 7 , L. Traylor 7 , J.H. DeVries 8
International Diabetes Center, Minneapolis, Minnesota, United States of America; 2 University of Miami Miller School of Medicine, Miami, Florida, United States of America; 3 Heart of England NHS Foundation Trust and University of Birmingham, Birmingham, United Kingdom; 4 Mercy Diabetes Center, Janesville, Wisconsin, United States of America; 5 Sanofi, Paris, France; 6 Sanofi, Frankfurt, Germany; 7 Sanofi Aventis U.S., Bridgewater, New Jersey, United States of America; 8 Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
Metformin, sulphonylurea, plus basal insulin is a three-drug combination indicated for type 2 diabetes (T2D) treatment by the ADA/EASD. This pooled patient-level data analysis evaluated efficacy and safety of insulin glargine plus metformin and sulphonylurea (IG-Met-SU) in treat-to-target RCTs. Eligible studies had ≥24 weeks duration, FPG target <100 mg/dL, and various comparators. From 9/17 basal insulin/OAD studies, 1,297 IG-M-SU-treated patients were identified: 54.6% men; mean (SD) age 58.2 (9.3) years; T2D duration 9.5 (6.3) years; BMI 31.2 (5.0) kg/m2; baseline A1C 8.7 (1.0) %; FPG 192.7 (52.4) mg/dL. Hypoglycaemia definitions included “overall” (with plasma glucose [PG] <70, <56, <50 mg/dL, or requiring assistance); “nocturnal” (between 0:01-5:59am); “severe” (requiring assistance); and documented “severe” (requiring assistance, with documented PG<36 mg/dL). Hypoglycaemia rate/incidence was estimated using negative binomial/general linear regression models, adjusting for baseline BMI and T2D duration. IG-Met-SU reduced A1C to 7.1 (0.9) % and FPG to 120.3 (38.6) mg/dL; 49% of patients reached A1C <7.0%. Adjusted mean (SE) hypoglycaemia event rates/patient-year for PG<70, <56, <50 mg/dL were: overall: 7.3 (0.35), 2.8 (0.15), 1.3 (0.09); nocturnal: 1.6 (0.12), 0.7 (0.06), 0.3 (0.03), respectively; severe: 0.09 (0.03); documented severe: 0.002 (0.002). Adjusted mean (SE) incidence (%) for PG<70, <56, <50 mg/dL was: overall: 58.2 (1.4), 40.3 (1.4), 25.3 (1.2); nocturnal: 25.0 (1.2), 16.0 (1.0), 8.4 (0.8), respectively; severe: 1.8 (0.4); documented severe: 0.07 (0.08). Regardless of hypoglycaemia definition, our analysis illustrates that most IG-Met-SU-treated patients achieve glycaemic targets over ≥24 weeks with low hypoglycaemia rates.
Study funding/editorial support provided by sanofi-aventis U.S.
A CASE OF A LATE ANASTOMOTIC LEAK POST GASTRIC BYPASS FOR OBESITY
D.S.Z.M. Boctor, I.G.I. Suliman, S. Low
Department of General Surgery, Queens Hospital, Barking, Havering & Redbridge University Hospitals NHS Trust, London, United Kingdom
Introduction: Roux-en-Y gastric bypass (RYGB) is one of the commonest bariatric procedures, and consists of the formation of a small gastric pouch with an anastomosis to a distal limb of jejunum. Anastomotic or staple line leaks are one of the most serious complications, and commonly occur within the first few post-operative weeks. There are very few documented cases of late leakage. Material and Methods: A 65 year old female presented to the emergency department with worsening abdominal pain and nausea which had been occurring intermittently since undergoing a laparoscopic RYGB eight months prior. On examination, she had generalized tenderness and guarding, maximally in the periumbilical region. Her blood tests revealed a raised white cell count of 14.9 and a raised C-reactive protein of 418.9. A Computer-assisted Tomography (CT) scan of the abdomen revealed free intra-peritoneal and retroperitoneal air, free fluid, and appearances in favour of a leak from the gastric bypass. Result: At laparoscopy, a large amount
of free fluid having the appearance of gastric contents was seen. Adhesions were separated but no obvious perforation could be identified and the procedure was then converted to an open laparotomy. A perforation at the gastrojejunal anastomosis was identified and was repaired using an omental patch. Conclusion: Bariatric surgery is a fast evolving surgical specialty with complications that need to be rapidly identified. Whilst underreported, late presentations of anastomotic leaks post RYGB can occur. Given its seriousness, it is vital that surgeons continue to consider this diagnosis when assessing patients many months post-operative.
CLINICAL CHARACTERISTICS OF TYPE 2 DIABETIC PATIENTS AT THE TIME OF INSULIN INITIATION IN TUNISIAN PATIENTS
K. Bouchrit, N. Khelifi, I. Kammoun, Z. Turki, C. Ben Slama
Endocrinology and Metabolism National Institute of Nutrition, Tunis, Tunisia
Introduction: The progressive history of type 2 diabetes requires exogenous insulin use for most patients. The objective of this study was to assess the clinical and biological patients' profile and the treatments that we proposed at initiation of insulin therapy. Patients and Methods: We conducted a retrospective study in 213 insulin-naïve type 2 diabetic Tunisian patients (96 men and 117 women) for whom treatment by insulin was initiated. Results: The mean age of our patients was 57.5±11 years. The mean BMI was 29±6 kg/m² and 35% were obese. Mean diabetes duration was 8.3±7.2 years. Most frequent comorbidities were hypertension (57.7%) and dyslipidemia (69%). Microangiopathy was more frequent than macroangiopathy: nephropathy in 22.5% of our patients, retinopathy in 14.1%, neuropathy in 2%, coronaropathy in 8% , peripheral arteriopathy in 6.6% and stroke in 3%. Mean HbA1c was 12.1±2.7% at the initiation of insulin treatment. The mean insulin dose was 0.5±0.2 UI/kg/day: 48% of the patients were treated by only basal insulin (NPH in more than 90%) and metformin was continued in 52% of cases in association with insulin treatment. Conclusion: At the time of insulin initiation, our patients presented with very high HbA1c and many complications related to diabetes. In our country, patients required more close monitoring of diabetes and more counseling for earlier insulin therapy initiation.
PATIENTS MORE OFTEN REACH A1C TARGET WHEN LIRAGLUTIDE IS ADDED TO AN SU VS. ADDING ROSIGLITAZONE OR PLACEBO
1 , S. Colagiuri 2 , C.B. Svendsen 3 , T.M. Jensen 3 , M. Marre 4
Department of Internal Medicine, Kantonsspital St. Gallen, St. Gallen, Switzerland; 2 The Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, Australia; 3 Novo Nordisk A/S, Soeborg, Denmark; 4 Department of Endocrinology, Diabetology and Nutrition, Bichat Hospital, Paris, France
Objective: To determine the proportions of patients reaching target A1C <7.0% with liraglutide vs. rosiglitazone or placebo, all as add-on to SU in a phase 3a trial (LEAD-1). Methods: „Time to A1C target‟ was analysed by a Cox hazards model, with current and previous treatment as fixed effects and baseline A1C as covariate. Results: The proportion of subjects reaching A1C <7.0% was greater with liraglutide vs. rosiglitazone or placebo. With liraglutide 1.8 mg, the estimated hazard ratio (HR) was 2.94 [95% CI: 2.21; 3.92], representing an estimated chance of reaching target at any given time during treatment almost three times as much for liraglutide 1.8 mg than rosiglitazone (p<0.0001). With liraglutide 1.2 mg, the HR was 2.08 [95% CI: 1.54; 2.79], representing an estimated chance of reaching target about two times higher than rosiglitazone (p<0.0001). As previously reported in LEAD-1, liraglutide added to an SU resulted in greater A1C improvements (–1.1% for both doses) than rosiglitazone (–0.4%; p<0.0001) or placebo (+0.2%; p<0.0001), with rates of minor hypoglycaemia <10% for all treatments (one major hypoglycaemic event in one subject receiving liraglutide 1.8 mg). Treatment with liraglutide 1.8 mg and 1.2 mg led to minimal weight changes of –0.2 kg (1.8 mg) and +0.3 kg (1.2 mg), whereas rosiglitazone led to notable weight gain of +2.1 kg (p<0.0001). Conclusion: Treatment with liraglutide added to an SU is significantly more likely to help patients achieve a target A1C.
GAPP2™ SURVEY: T2DM PATIENTS USING INSULIN ANALOGUE WHO DOSE IRREGULARLY REPORT MORE HYPOS
1 , M. Peyrot 2 , A. Rana 3 , A.H. Barnett 4
The Brod Group, Mill Valley, California, United States of America; 2 Loyola University Maryland, Baltimore, Maryland, United States of America; 3 Novo Nordisk, Copenhagen, Denmark; 4 Heart of England NHS Foundation Trust and University of Birmingham, United Kingdom
Objective: An international online survey of type 2 diabetes (T2DM) patients using insulin analogues (IAs), investigated links between self-treated hypoglycaemia (hypos), dosing irregularities and patient characteristics, and sought prescriber perspectives on the impact of hypos on T2DM management. Methods: Hypo data on 3042 T2DM patients on IA and perspectives from 1222 prescribers (primary/secondary care physicians), from 6 countries (US, Canada, Japan, UK, Germany, Denmark) are presented. Results: Hypos were common. Significantly more women (43% vs 31% male) and basal bolus (45% vs 25% basal only) patients reported hypos in the last 30 days. The proportion of patients reporting hypos also tended to increase with duration of insulin use. Of patients reporting hypos, the proportion reporting 5+ events in the last 30 days was similar regardless of gender, regimen or duration of use (~20%). Significantly more patients who had missed, mistimed or reduced their BI dose in the last 30 days reported a hypo than those who had not (41% vs 34%, 43% vs 34%, 56% vs 30%). Prescribers said they regularly discussed hypos. However, in the last 30 days 35% had discussed hypos with <25% of IA patients and one in five (22% BI and 21% BB) said this was because they were more concerned about patients taking medication as prescribed. Conclusions: Hypos are common in T2DM IA patients and greater prescriber awareness may be needed of hypo risk amongst women, long term insulin users and those on BB regimens as well as those with poor BI insulin taking behaviour.
ASSOCIATION BETWEEN HEALTH PRODUCTION PROFILES AND ABDOMINAL OBESITY IN CHILEAN CHILDREN AND ADOLESCENTS: A COMPARATIVE ANALYSIS
1 , P. Correa Burrows 2
Institute of Nutrition and Food Technology INTA, University of Chile, Chile; 2 Department of Applied Economics II, Rey Juan Carlos University URJC, Spain
Background: Abdominal obesity (AO) is associated with high cardiovascular and metabolic risk; Western diet and sedentarism are strong environmental determinants. The „health production‟ model posits that individuals are born with a certain amount of „health stock‟, which is affected by genes and environment. Health stock can be augmented or not over life, depending on the amount of inputs individuals allocate to the production of health since early stages, including individual behaviours such as diet and exercise. Objective: We study the association between abdominal obesity and health production in Chilean adolescents (1,656) and children (1,078) selected through random sampling. Methodology: We used an indicator that considered the quality of food intake and physical activity, establishing three categories: good (GHP), intermediate (IHP) and poor health producers (PHP). AO was diagnosed according ATP III in both groups. IDF definition was also used for diagnosis in adolescents. Results: There was 31% of GHP, 32% of IHP and 38% of PHP in adolescents, while in children 24%, 29% and 47%, respectively. In adolescents, the prevalence of AO was significantly higher at lower health production (p<0.01 and p<0.000). In children, however, the relationship appeared not to be significant. Behaving as PHP significantly increased the risk of AO compared to GHP, both in children (OR: 2.14 CI: 1.21-3.78) and adolescents (ATP III: OR: 2.71 CI: 1.94-3.81; IDF: OR: 2.41 CI: 1.48-3.95). Adolescents behaving as IHP also showed a significantly higher risk of AO compared to GHP individuals. Conclusion: Lower health production entails a higher risk of AO since early stages. Results support the association between AO and health production in teenagers.
CARDIOVASCULAR RISK IN CHILEAN ADOLESCENTS: THE ROLE OF FAMILY HISTORY OF TYPE 2 DIABETES
1 , M. Reyes 1 , V. De Toro 1 , P. Correa Burrows 2 , E. Blanco 3 , B. Lozoff 4 , M. Castillo 1 , S. Gahagan 3
Institute of Nutrition and Food Technology INTA, University of Chile, Chile; 2 Department of Applied Economics II, Rey Juan Carlos University, Spain; 3 Division of Child Development and Community Health, University of California San Diego, United States of America; 4 Center for Human Growth and Development, University of Michigan, United States of America
Background: Family history of type-2 diabetes mellitus (FHDM) and obesity raises the risk of insulin resistance (IR), Metabolic syndrome (MetS) and type-2 diabetes. Dietary and western lifestyle patterns are strong determinant. In Chile, between 1993 and 2001, the prevalence of obesity and diabetes increased from 21.8% to 32% and 3.8% to 10.1% respectively. Objective: To study the association of FHDM and obesity with IR and MetS in a cohort of Chilean adolescents. Design: From a longitudinal study, 498 adolescents (16.7 years old), we measured: BMI, waist circumference, blood pressure, triglycerides, HDL-chol, glucose, insulin, HOMA-IR, and physical activity (PA) habits. MetS prevalence was based on the Cook criteria. We also calculated a Mets risk score. To measure the influence of FHDM, obesity and PA on MetS and IR, linear and logistic regressions were used. Results: Adolescents with FHDM had significantly higher prevalence of abdominal obesity, high diastolic pressure, fasting hyperglycemia and IR, compared to adolescents without family history. FHDM, obesity and low PA were significantly associated with higher HOMA-IR (p<0.01). Obesity, male gender and low PA were associated with higher risk of MetS (p<0.001); association with FHDM was insignificant. Conclusions: In our sample, FHDM was associated with higher risk of MetS, but not with higher risk of IR, while obesity and low physical activity were associated with both outcomes.
PEPTIDES P217 AND P290 IMPROVES THE SALIVARY GLANDS OF DIABETIC MICE
1 , R.D. Mâncio 1 , M.A. Dias 1 , R.E. da Silva 1 , F. Rojas 1 , L. Peroni 1 , P.K. Picardi 1 , R.S.F. Júnior 2
Faculty of Medicine of Jundiaí, Jundiaí, Brazil; 2 CEVAP - UNESP
Diabetes affects the metabolism promoting damage in different tissues, including salivary glands. Current treatments, such as insulin, are ineffective to recovery of these tissues. Thus, the aim of this study was to evaluate the effects of peptides P217 and P290 in the recovery of salivary glands of diabetic NOD mice. Animals were divided into three groups; Group I (7 Balb/C mice), Group II (7 NOD mice), and Group III (7 NOD mice/treated). Group III received the peptides during a total period of 21 days. Groups I and II received saline solution to simulate the experimental treatment. After treatment salivary glands samples were analyzed by light microscopy and stereology. Treated animals consumed less liquid and solid. Reduction of body weight was observed in untreated animals. High levels of glucose were observed in animals of group II, while in treated diabetic animals, a reduction was observed in these levels. Inflammatory process was not observed in salivary glands of group I. Intense inflammatory process was observed in untreated diabetic animals. Reduction of inflammatory process was observed in treated diabetic mice. In these animals were observed decrease of lymphocytes and increase of neutrophils. Tissue restructuring of parotid and submandibular glands was observed after the immunotherapy. This treatment was effective in the recovery of salivary acinar cells, contributed also to homeostasis of body metabolism and reduction of inflammatory process, with increase of neutrophils that suggest an attempt of tissue reorganization. Thus, this immunomodulation promoted a beneficial effect on the recovery of these tissues.
EVALUATION OF A BASAL-PLUS REGIMEN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS OF DIFFERENT AGES: A POOLED ANALYSIS
1 , M.P. Dain 1 , S. Del Prato 2 , M. Lankisch 3 , J. Lin 4 , D. Owens 5 , G. Dailey 6
Sanofi, Paris, France; 2 University of Pisa, Pisa, Italy; 3 German Diabetes Center, Düsseldorf, Germany; 4 Novosys Health, Flemington, New Jersey, USA; 5 Cardiff University, Cardiff, United Kingdom; 6 Scripps Clinic and Research Foundation, La Jolla, California, United States of America
Aims: The basal-plus regimen is often used in insulin intensification for patients with type 2 diabetes mellitus. We evaluated the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin glargine in patients aged < 55, 55–64 and ≥ 65 years. Methods: Data was pooled from 4 randomised, multi-centre studies in patients with poor glycaemic control initiated on basal insulin glargine to which insulin glulisine was added once daily for up to 6 months. The glargine dose was initially titrated to protocol-defined blood glucose (BG) targets in 2 studies. Glulisine was introduced and dose-titrated in all 4 studies to protocol-defined fasting/pre-prandial or post-prandial BG targets. Demographic, efficacy and safety data were collected at baseline and at each study's endpoint. Results: 713 patients were analysed. The basal-plus regimen significantly decreased HbA1c in all age groups between baseline and study end (P < 0.001) with significantly greater reductions for the 2 older age groups (both –0.5 ±SD 0.8) compared with patients aged < 55 years (–0.3 ±SD 1.0). Target HbA1c (< 7%) was reached by 42.7%, 43.9% and 48.3% in the < 55, 55–64 and ≥ 65 years cohorts, respectively. The incidence of severe hypoglycaemia was similar across all ages (0.01–0.04 events/year), whilst there was a trend toward less weight change in the older groups. Conclusion: The basal-plus regimen significantly reduced HbA1c across all age groups. Along with low rates of severe hypoglycaemia, these findings are particularly encouraging for older patients.
THE DUAL PPARα/δ AGONIST GFT505 IMPROVES HEPATIC AND PERIPHERAL INSULIN SENSITIVITY IN ABDOMINALLY OBESE SUBJECTS
1 , R. Hanf 2 , S. Lambert-Porcheron 3 , Y. Zaïr 1 , L. Flet 4 , H. Vidal 5 , B. Staels 6 , M. Laville 3
Department of Endocrinology, Nantes University Hospital, France; 2 Genfit, loos, France; 3 Centre de Recherche en Nutrition Humaine Rhone Alpes, Lyon, France; 4 Pharmacy, Nanets University Hospital, France; 5 INSERM UMR 1060, Lyon, France, 6 UMR 1011 Inserm, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France
The development of new insulin-sensitizers is an unmet need in the treatment of type 2 diabetes. GFT505 is a new dual PPARα/δ agonist, which improves multiple metabolic parameters in patients with pre-diabetes or combined dyslipidemia. Here, we determined the effect of GFT505 on insulin sensitivity in 22 abdominally obese male subjects, using a 2-step hyperinsulinemic-euglycemic clamp. This randomised, placebo-controlled study was performed in a cross-over design with two 8-week treatment periods, separated by a 6-week wash-out period. Skeletal muscle biopsies were performed at the end of the first treatment period. Compared to placebo, GFT505 significantly increased the glucose infusion rate at the 2nd step of the clamp (primary outcome) by 21% (3.79 ± 1.29 vs 3.13 ± 1.48 mg/kg.min; p=0.048), reflecting an improvement in peripheral insulin sensitivity. Moreover, GFT505 potentiated insulin-inhibition of hepatic glucose production by 44% (-49.2% ± 19.3 vs -34.3% ± 17.4; p=0.0016), indicating an improvement of hepatic insulin sensitivity. There was no significant induction of either PPARα or δ target genes in skeletal muscle, suggesting a liver-targeted action of GFT505. GFT505 improved the plasma lipid profile with a decrease of triglycerides (-21.0%, p=0.003),
free fatty acids (-11.0%, p=0.03) and LDL-C (-13.1%, p=0.006). GFT505 also reduced fibrinogen (-15.0%, p=0.04), haptoglobin (-10.1%, p=0.03) and the liver enzymes γGT (-30.4%, p=0.003) and ALT (-20.5%, p=0.004) in plasma. There was no serious adverse event related to GFT505. This study demonstrates that GFT505 is an insulin-sensitizer, which is an attractive and safe candidate for the treatment of metabolic disorders related to insulin resistance.
EFFICACY AND SAFETY OF INSULIN GLARGINE AMONG TYPE 1 DIABETES PATIENTS IN THE US: ANALYSIS OF THE IMPACT DATABASE
1 , E. Wang 2 , A. Cali 3 , M.P. Dain 3 , J. Lin 4 , S. Garg 1
Barbara Davis Center for Childhood Diabetes, Aurora, Colorado, United States of America; 2 Sanofi, Bridgewater, New Jersey, United States of America; 3 Sanofi, Paris, France; 4 Novosys Health, Flemington, New Jersey, United States of America
Aims: Multiple-dose insulin injections or continuous subcutaneous insulin infusions are recommended in type 1 diabetes mellitus (T1DM). We evaluated glycaemic control and hypoglycaemia when replacing non-glargine insulin therapy with insulin glargine in patients with T1DM in the United States. Methods: Data (Jan 2006–Sept 2011) were extracted from a US insurance claims database of > 60 million patients. Study period was defined as the 12-month period prior to and following first insulin glargine use (baseline and follow-up, respectively). HbA1c reduction, hypoglycaemic rates, and „all-cause‟ and „diabetes-related‟ hospitalisations and emergency room (ER) visits, were compared at baseline and follow-up. Results: 373 patients with T1DM previously treated with insulin were identified (54.7% female; mean age 38.5 years). Before starting insulin glargine, 41.0% were using basal insulins, as well as insulin aspart (41.8%) and/or lispro (37.0%). Insulin glargine use was associated with significant reductions in HbA1c (Δ from baseline, –0.15%, P = 0.04). Hypoglycaemia-related ER visits did not differ between follow-up and baseline periods (both 5.9%; NS); however, the prevalence of hospitalisations was significantly lower following insulin glargine use for any-cause (15.0% vs 26.0%; P < 0.001) and diabetes-related events (12.3% vs 22.3%; P < 0.001). Any-cause ER visits did not differ between the groups, yet there were significantly fewer diabetes-related ER visits at follow-up compared with baseline (22.0% vs 28.2%; P = 0.03). Conclusion: These data suggest insulin glargine use is associated with improvements in glycaemic control, fewer hospitalisations (including hypoglycaemia-related) and diabetes-related ER visits compared with prior non-glargine insulin therapy.
THE ROLE OF HEALTH PRODUCTION AS A DETERMINANT OF METS IN A COHORT OF CHILEAN ADOLESCENTS
P. Correa Burrows
1 , M. Reyes 2 , D. Chavez-Yenter 3 , E. Blanco 3 , S. Gahagan 3 , R.A. Burrows 2
Department of Applied Economics II, Rey Juan Carlos University, Spain; 2 Institute of Nutrition and Food Technology INTA, University of Chile, Chile; 3 UCGHI Global Health Fellowship, Michigan State University, United States of America; 4 Division of Child Development and Community Health, University of California, San Diego, United States of America
Background: The „health production‟ model posits that individuals are born with a certain amount of „health stock‟, which is affected by genes and environment. This stock depreciates or increases over life, and can be affected by individual behaviors, including exercise and dieting. Objective: In 491 adolescents from a longitudinal follow-up, we studied the association between health production and MetS in adolescence using multivariate analysis. Methodology: We used self-reported physical activity to establish three categories of health production: „good‟ (GHP), „intermediate‟ (IHP) and „poor‟ (PHP). To assess the association between health production and MetS (IDF criteria), we used multiple linear and logistic regressions, controlling for gender, anthropometry and cardio-metabolic characteristics. Results: Prevalence of MetS was significantly higher (p<0.01) in the poor health production group [15.3%], compared to the good [5.1%] and intermediate group [5.5%], respectively. PHP significantly increased HOMA-IR (p<0.05), and the effect of abdominal obesity (p<0.01), SystBP (p<0.01), and DiastBP (p<0.001) in the MetS score. Adolescents behaving as PHP were significantly more likely to suffer from MetS compared to IHP and GHP adolescents (adjusted OR: 3.98 CI: 1.8-8.9). Conclusions: Our results indicate that poor health production in adolescence, as defined by physical activity, depreciates „health stock‟. In our sample health production is associated with negative cardiovascular and metabolic risk factors. Similarly, there was a significant association between risk of MetS and poor health production.
EVALUATION OF A BASAL-BOLUS REGIMEN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS OF DIFFERENT AGES: A POOLED ANALYSIS
1 , A. Cali 2 , J. Lin 3 , E. Wang 4
Scripps Clinic and Research Foundation, La Jolla, California, United States of America; 2 Sanofi, Paris, France; 3 Novosys Health, Flemington, New Jersey, United States of America; 4 Sanofi, Bridgewater, New Jersey, United States of America
Aims: Basal-bolus refers to a type of diabetes treatment intensification regimen that is prescribed for both young and older patients with type 2 diabetes mellitus. We evaluated the efficacy and safety of adding mealtime insulin glulisine to basal insulin in patients aged < 55, 55–64 and > 65 years. Methods: Data were pooled from 5 randomised, multi-centre studies in patients with poor glycaemic control initiated on basal insulin to which insulin glulisine was added at mealtime. Patients were treated for up to 6 months. Demographic, efficacy and safety data were collected at baseline and at each study's endpoint. Results: 1413 patients were analysed, of which 32.2% (n=455) were < 55 years, 42.6% (n=602) were 55–64 years and 25.2% (n=356) were ≥ 65 years. The basal-bolus regimen resulted in similar decreases in HbA1c from baseline to study end in each of the 3 age groups (all Δ -0.8; P < 0.001). Target HbA1c (< 7%) was reached by 45.5%, 50.3% and 54.5% in the < 55, 55–64 and > 65 years cohorts, respectively. The incidence of severe hypoglycaemia was similar across all ages (0.1–0.3 events/year); however, there was less weight gain in the 2 older groups compared to younger patients. Conclusion: These findings suggest that a basal-bolus treatment regimen significantly and clinically reduces HbA1c across different age groups, including older patients, with similar rates of severe hypoglycaemia. In addition, there was less weight gain in the older patients.
PLASMA INSULIN GLARGINE AND ITS METABOLITE M1 AND M2 AFTER SUBCUTANEOUS INJECTION OF THERAPEUTIC DOSES IN YOUNG CHILDREN WITH T1DM: RESULTS FROM THE PRESCHOOL STUDY
1 , P. Johnston 2 , G. Xiang 3 , A. Cali 4 , M.P. Dain 4 , A. Philotheou 5
Kinder und Jugendkrakenhaus 'Auf der Bult', Hannover, Germany; 2 Sanofi, Bridgewater, New Jersey, United States of America; 3 Fewmo Technology Company LTD, Beijing, China; 4 Sanofi, Paris, France; 5 UCT Private Academic Hospital, Cape Town, South Africa
Aims: In vivo, insulin glargine is converted into 2 main metabolites (M1 and M2) following subcutaneous injection. In vitro, insulin glargine exhibits greater binding affinity for IGF-1R and greater mitogenic properties compared with human insulin; conversely M1 and M2 exhibit lower binding affinity and similar mitogenicity. M1 is the principal circulating active insulin glargine component in adults with type 1 or 2 diabetes mellitus (T1DM/T2DM). This study aimed to quantify plasma concentrations of insulin glargine, M1 and M2 after subcutaneous injection of insulin glargine in young children with T1DM. Methods: Children with T1DM aged 1–6 years from the PRESCHOOL study (n=61) were treated with insulin glargine for 24 weeks; blood samples were drawn ~24 hours after last dose at Weeks 1, 2 and 4. Ctrough plasma levels were determined using immunoaffinity purification and LC-MS/MS. Lower limit of
quantification (LLOQ) was 0.2 ng/mL. Results: M1 was the principal active circulating insulin glargine component in plasma. Mean±SD plasma M1 Ctrough values were 0.580±0.786, 0.458±0.700 and 0.452±0.583 ng/mL at Weeks 1, 2 and 4, respectively. Mean insulin glargine and M2 concentrations were below the LLOQ, indicating no insulin glargine or M2 accumulation. Similar results have been observed in adults. Conclusions: For young children with T1DM, the principal circulating active insulin glargine component is M1; M1 has lower affinity for the IGF-1R than human insulin but similar mitogenicity. These data provide added evidence for the safety profile of insulin glargine in young children; however, further studies are needed.
DIABETES CLINIC PERFORMANCE OVER A PERIOD OF FOUR YEARS AT CONQUEST HOSPITAL, HASTINGS, UK
U.K. Dashora, A. Al-Abdullah
Conquest Hospital, Hastings, United Kingdom
National Institute of Clinical Excellence, UK has set an HbA1c target of 7.5 % and a total cholesterol target of 4 mmol/l for people with diabetes. We searched our electronic record system for achievement of these targets by patients between January to December 2007, 2008 and 2009 and 2010. Out of 658, 1150 and 1181 and 1404 patients with HbA1c records, only 48%, 50%, 53% and 53.7% achieved the HbA1c target of 7.5 %. The overall mean ± SD was 7.9 ±1.9 %, 7.7 ±1.7%, 7.7 ±1.7% and 8.0 ±2.0%. The proportion of people achieving HbA1c target of 7.5 % was higher than available figures from hospital clinics like Southampton (30 %, p<0.0001) but similar to overall figures and primary care data from Germany (55%, NS), London (54%, NS) and National Diabetes Audit UK (56 %, NS). Over the same periods; 803, 1150, 1181 and 1373 people had total cholesterol recorded with 39%, 47% and 49% and 44.7 %reaching the targets of 4 mmol/l with mean 4.3±1.1, 4.3 ±1.2, 4.24 ± 1.1 and 4.35 ±1.1 mmol/l. . The percentage of people achieving this target was lower than published figures from London (64%, p<0.0001). The achievement of targets is low in our clinic and a strategic reorganization of service with more intensive follow-up may be required to achieve these targets. The implications for new to follow-up ratio and Payment By Results will be discussed.
EFFECT OF GREEN TEA ON ADIPOSITY, METABOLIC PROFILE, BLOOD PRESSURE AND ENDOTHELIAL FUNCTION IN OBESE PRE-HYPERTENSIVE WOMEN
L. de Paula Nogueira, D.T. Valença, M.G. Rodrigues, E.R. Soares, M.R.S.G. Torres, R.L. Carvalho, J.F. Noguiera Neto, A.F. Sanjuliani
Discipline of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
Background: Cardiovascular diseases are the leading cause of mortality in Western countries. Some studies have suggested that green tea has beneficial effects on different cardiovascular risk factors. However, others have failed to show such an association. Objective: To evaluate the effects of green tea on body weight, waist circumference, metabolic profile, inflammation, blood pressure and endothelial function in obese pre-hypertensive women. Methods: Crossover randomized controlled double-blinded trial. Twenty women with obesity and pre-hypertension, aged 28-59 years, with stable body weight were randomized to receive a daily supplement of 3 capsules that contained either 500mg of green tea extract (GTE) or a matching placebo for 4 weeks, with a washout period of 2 weeks between the treatments. Endothelial function was evaluated by peripheral arterial tonometry method, using Endo-PAT 2000®. Results: After administration of GTE compared with placebo there were no significant changes in body mass index (-0.03±0.07vs.-0.09±0.09kg/m2; p=0.63), waist circumference (0.11±0.27vs.-0.35±0.41cm; p=0.37), glucose (0.78±1.81vs.-3.78±2.08mg/dl; p=0.11), total-cholesterol (5.85±4.24vs.-4.25±5.57mg/dl; p=0.16), LDL-cholesterol (2.35±4.4vs.-7.7±5.54mg/dl; p=0.16), HDL-cholesterol (1.4±1.4vs.2.15±1.71mg/dl; p=0.74), triglycerides (10.95±11.53vs.7.05±9.74mg/dl; p=0.80), high-sensitive C reactive protein (0.01±0.07vs.0.05±0.08mg/dl; p=0.70), casual systolic blood pressure (-2.45±1.53vs.2.94±1.73mmHg; p=0,83), casual diastolic blood pressure (-0.95±0.85vs.-2.23±1.19mmHg; p=0.38), systolic blood pressure evaluated by Ambulatory Blood Pressure Monitoring (ABPM) over 24h (-2.15±1.53vs.1.05±1.34mmHg; p=0.13), diastolic blood pressure evaluated by ABPM over 24h (-0.6±1.1vs.0.5±1.1mmHg; p=0.49), and reactive hyperemia index (0.24±0.18vs.-0.09±0.09; p=0.12). Conclusions: The findings of the present study suggest that green teen extract supplementation in obese pre-hypertensive individual does not improve adiposity, metabolic profile, blood pressure and endothelial function.
LIPID COMPOSITION OF PLATELET MEMBRANES IN PATIENTS WITH RENOCARDIAL SYNDROME
Sumy State University, Medical Institute, Sumy, Ukraine
The question of the platelets` role in pathogenesis of immune inflammation is topical in patients with combination of chronic kidney disease and hypertension, namely renocardial syndrome. Platelets` over-stimulation turns into pathological process and progression of inflammation. Aim: to study lipid composition of platelet membranes at renocardial syndrome and role in development of inflammation and membrandestructive processes. Results: All 53 patients with renocardial syndrome had changes of lipid fractional composition of platelet membranes. Levels of total lipids (4.64±0.28 g/l), and cholesterol (1.31±0.11 g/l) were increased significantly (p<0.05), while the level of sphingomyelin (SM), phosphatidylcholine, phosphatidylserine were reduced by 13.2%, 30.8% and 11.2%, respectively. The median concentration of phosphoinozitolphosphate (PhI) was reduced at 2.03 times compared to the control in all patients, and the most changes were observed in the nephrotic form of glomerulonephritis. Least fraction PhI decreased with latent nephritis at 0.61 times (sign of hydrolysis, resulting to platelets` activation). In all forms of glomerulonephritis the percentage of SM decreased: hypertonic form with preserved renal function at 1.49 times, a latent form - 1.45, hypertension and chronic renal failure nephrotic forms - 1.53 times, indicating the destruction of outer membrane cells. Phosphatidylethanolamine fraction was also reduced in all patients. Pronounced lysophosphatidylcholine increase (2.05 times) was noted in nephrotic form, indicating that destabilization of their structure and high permeability. Conclusion: At renocardial syndrome there is accumulation of lizoform phospholipids in platelets` membranes regardless of degree of renal dysfunction and clinical symptoms, indicating intensification of lipid peroxidation and accumulation of bioactive substances processes.
ALTERATION OF MYOCARDIAL OXIDATIVE STRESS PATTERNED BY OBESITY IN CABG PATIENTS
1 , Y. Gramlich 2 , M. Oelze 2 , U. Hink 2 , A. Daiber 2 , T. Münzel 2 , C.F. Vahl 1
Department of Cardiothoracic and Vascular Surgery, University of Mainz, Germany; 2 Department of Cardiology, University of Mainz, Germany
Objectives: Myocardial contractility is impaired in myocardium from patients with increased body-mass-index (BMI). Animal studies point towards relevant compensatory mechanisms in cardiovascular disease states due to altered expression of antioxidative enzymes, i.e. mitochondrial aldehyde-dehydroxygenase (ALDH2), endothelial NO-synthase (eNOS) and the tetrahydrobiopterin (BH4)-synthesizing enzyme dihydrofolate reductase (DHFR). Methods: From 61 subsequent CABG patients we harvested excessive, right atrial myocardial tissue emerging from operative connection to extracorporal circulation. Patients were assigned to either the „Control‟ (n=19, normal BMI), the „Obesity‟ (n=25, BMI > 26 for men / >25 for women) or the „Adiposity‟ (n=17, BMI > 30) group. In myocardial tissue we looked for altered protein expression of antioxidative
enzymes by Western or Dot blotting. Mean values derived from Control group were defined as 100% expression. Superoxide concentrations and functional enzymes as mitochondrial aldehyde-dehydroxygenase (ALDH2), endothelial NO-synthase (eNOS) and the tetrahydrobiopterin (BH4)-synthesizing enzyme dihydrofolate reductase (DHFR) were measured. Results: In myocardium of obese patients superoxide levels were increased to >120% expression of Control. Resulting in functional enzymatic changes: not only the ALDH2 was significantly attenuated in the „Adiposity‟ group (75% vs. Ctr., p=0.002) but also the DHFR stated fewer expression in the „Obesity‟ (74% vs. Ctr., p=0.018) and in the „Adiposity‟ group (63% vs. Ctr., p=0.004). There was currently no group difference in expression of eNOS. Conclusions: Myocardium from obese patients undergoing CABG displays modulated expression of oxidative stress sensitive enzymes. Elevated superoxide levels as well as attenuated expression of ALDH2 and DHFR are suggestive for an increased myocardial oxidative stress in obese patients. These data contribute to an explanation of impaired myocardial contractiliy in patients with increased BMI.
SIGNS OF AN ELEVATED MYOCARDIAL OXIDATIVE STRESS IN DIABETIC CABG PATIENTS
1 , Y. Gramlich 2 , M. Oelze 2 , U. Hink 2 , A. Daiber 2 , T. Münzel 2 , C.F. Vahl 1
Department of Cardiothoracic and Vascular Surgery, University of Mainz, Germany; 2 Department of Cardiology, University of Mainz, Germany
Objectives: Hyperglycemia is suspected to induce oxidative stress which may induce morpho-physiological alterations of the myocardial texture (e.g. fibrosis, endothelial dysfunction). Animal studies point towards relevant compensatory mechanisms due to altered expression of antioxidative enzymes. This study was performed as an attempt to understand modifications of oxidative stress parameters in myocardium of diabetic CABG patients. Methods: Right atrial myocardium was obtained from 59 consecutive patients undergoing CABG. Patients were assigned to either the Control (n=41, no diabetes) or the Diabetic (n=18, IDDM/NIDDM) group. In myocardial tissue protein expression of antioxidative enzymes was analyzed by Western or Dot blotting. Mean values derived from Control group were defined as 100% expression. Superoxide concentrations and functional enzymes, such as mitochondrial aldehyde-dehydroxygenase (ALDH2), endothelial NO-synthase (eNOS), the tetrahydrobiopterin (BH4)-synthesizing enzyme dihydrofolate reductase (DHFR) and heme oxygenase-1 (HO-1) were measured. For statistical analysis the Mann-Whitney-U-test was used. Results: In diabetic myocardium superoxide levels were increased to 136±15% (vs. 100% Control group). Resulting in functional enzymatic changes: the DHFR expression was reduced in diabetics (86±20%); there was no group difference in expression of ALDH2. Activated eNOS was a significantly attenuated in diabetic myocardium (p=0.025). The HO-1 was significantly elevated in diabetic patients (p=0.019). Conclusion: Myocardium from diabetic patients undergoing CABG displays modulated expression of oxidative stress sensitive enzymes. Elevated superoxide levels and attenuated expression of activated eNOS and DHFR as well as elevated HO-1 are suggestive for an increased myocardial oxidative stress. These may partially account for pathophysiological alterations in diabetic cardiomyopathy.
EFFECTS OF DPP-4 INHIBITORS IN SALIVARY GLANDS OF SPONTANEOUSLY DIABETIC MICE
M.A. Dias, A.L.D. da Silva Faria, V.B. Leme, E.E. Mayoral, R. Netto, R.E. da Silva, R.D. Mâncio, E.J. Caldeira
Faculty of Medicine of Jundiaí, Jundiaí, Brazil
Incretin-based therapies are effective in patients possessing certain levels of preserved beta-cell function. However, doubts still exist regarding the efficacy of this treatment in the recovery of tissues damaged by type I diabetes. Thus, the objective of this study was to evaluate the effect of MKO431 in salivary glands of diabetic NOD mice. Ten NOD mice were divided into two groups of 5 animals each: groups I and II. Group II was treated with MKO431during 4 weeks. Group I was conducted in the same way without receiving, however, any treatment. Glucose level was monitored during treatment and salivary glands samples were collected for analysis in transmitted and polarized light microscopy. Non-treated animals consumed more liquid and less solid, when compared to animals of group II. Despite this, both groups had reduced body mass. High glucose levels were observed in non-treated animals, while in treated animals, reduction of these levels was observed. Tissue restructuring was observed in animals submitted to MKO431 therapy. In the group I; type I collagen fibers were increased in parotid and in submandibular glands when compared to treated group. No differences were observed in the type II collagen. Regarding type III was observed increased in both glands of treated animals. Thus, the therapy might have been important for the body homeostasis of diabetic animals. In addition, this therapy helped to recovery of salivary glands, mainly in relation to extracellular matrix reorganization, thus contributing for the reestablishment of tissues damaged by the hyperglycemic condition (Support FAPESP:11/02262-7).
NEEDLE ASPIRATION FOR HEALTHY SKIN PUNCTURE (HSP) OUTPATIENT IN DIABETIC FOOT INFECTED
N.S. Segura, R. Rafael, L.M. Carrio, C.L. Vasl
Centro de Diabetes Dr. Alberto Maggio, Buenos Aires, Argentina
Introduction: The Infection in the diabetic foot is a complex problem, because it has high cost and high mortality. It is considered an aggravating factor on pre-existing injury that changes the treatment and prognosis of the wound. 55% of these lesions manifest as severe infections, complicated by osteomyelitis and generating up to 50% of amputations.1 Objective: To determine microorganisms most frequently isolated from infected diabetic foot lesions in the city of Malvinas Argentinas, Buenos Aires, Argentina, between November 2011 and July 2012. Materials and Methods: An observational, longitudinal study. 181 samples of healthy skin puncture by direct and culture for aerobic species. Bone samples were omitted. The results were expressed in absolute numbers and percentages. Results: HSP without insulation 61; with insulation 120. Of HSP with insulation, 75 isolates of Gram +: Staphylococcus aureus 32 (42.66%), enterococcus 16 (21.33%), coagulase-negative staphylococci 21 (28%), streptococcus 1 (1.33%), Morganella 5 (6.66%). GRAM-71 isolates: Pseudomonas aeruginosa 10 (14.08%), Klebsiella 14 (19.71%), Escherichia coli 22 (30.98%), Proteus 13 (18.3%), enterobacter 1 (1.33 %); BGNNF 3 (4.22%); citrobacter 7 (9.85%); yersinia 1 (1.4%). Conclusion: The most frequently isolated pathogen GRAM + was Staphylococcus aureus, followed by coagulase-negative Staphylococcus and Enterococcus. GRAM - Escherichia coli followed by Klebsiella and Pseudomonas. The HSP taken with proper technique and appropriate sterility has high revenue for the isolation of pathogens from infected diabetic foot, and is also a minimally invasive and inexpensive technique.
HYPERURICEMY AS A COMPONENT METABOLIC SYNDROME IN MENOPAUSAL WOMEN
1 , I. Dorofeev 2
North Western State Medical University, Saint Petersburg, Russia; 2 City Hospital N26, Saint Petersburg, Russia
The aim of the research is to discover presence of hyperuricemy of women during menopause. Methods: 281 women participated, 198 of with CHD – main group, and 83 without CHD – control group. The average age of the patients the main group 51,5±5,4; the control – 49,8±5,03 years. Along with clinical and functional methods, body-weight index (BWI kg/m²), waist measurements (WM), the ratio of waist measurements to hips measurements (WM/HM), glucose, insulin, uric acid levels in blood plasma. Results: The uric acid concentration level among women suffering from CHD the tendency to its increase was discovered in comparison with the women without CHD. Thus,
average uric acid concentration in blood plasma of the explored group equaled to 335,0±26,8; the control - 298,5±29,4 mcm/l. The hyperuricemy frequency among patients with metabolic syndrome equaled to 56,7%, without –25,2%. In the process of conducting correlation analysis with regards to dependence of uric acid concentration in blood plasma with components of metabolic syndrome it was determined that significant direct correlation occurred between the value of uric acid concentration on the one hand and showings reflecting obesity level on the other hand (BWI, WM/HM) (р<0,01). Besides, uric acid significantly and directly correlated with triglycerides (р<0,001), glycemia level (р<0,01), basal insulin (р<0,01), HS LDL (р<0,05), arterial hypertension (р<0,05). Conclusion: Women with CHD during menopausal period have serum uric acid level, which significantly correlates with the other components of menopausal metabolic syndrome, which makes it possible to assess hyperuricemy as its diagnostic criterion.
EVALUATION OF THE LEPR AND ERS1 GENES METHYLATIONS IN PRE AND POST MENOPAUSAL WOMEN
J.C. dos Santos
1 , H.L. Wang 1 , M.C. Almeida 1 , A.R. Garofalo 1 , M.F. Sampaio 1 , M.H. Hirata 2 , A. Bertolami 1 , M.C. Bertolami 1 , P.H.O. Lima 1
Dante Pazzanese Institute of Cardiology, Molecular Biology, Sao Paulo, Brazil; 2 Faculty of Pharmaceutical Sciences, Sao Paulo University, Sao Paulo, Brazil
DNA methylation regulates gene expression in mammals, which is potentially reversible and modulated by environmental and dietary intervention. Changes in leptin receptor (LEPR) and estrogen receptor 1 (ESR1) seem to influence carbohydrate metabolism and also insulin levels may be affected in post menopausal women. The aim of this study is to evaluate the presence of LEPR and ESR1 genes methylations in pre and post menopause women. 87 women aged 40 to 65 years were screened at the Dante Pazzanese Institute of Cardiology (preliminary report). The patients were grouped: pre menopausal women (N=18) and post menopausal women (N=69). Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing in white blood cells (WBC). Data showed the following hormonal parameters with significant differences: LH (4.07±3.95; 28.84±12.70), FSH (7.61±10.26; 73.07±31.16), Estradiol (114.83±137.36; 24.98±51.54) and Progesterone (2.23±3.43; 0.38±0.62) between in the groups pre menopausal and post menopausal respectively. The insulin levels were decreased in post-menopause group, however no significance was found between the groups (8.49±4.23; 7.76±4.55, p=0.40). The median LEPR and ESR1 genes methylations were higher in the pre menopausal compared to post menopausal (75% vs 57% and 23% vs 15% respectively). Furthermore was found positive correlation between DNA methylation levels of genes LEPR and ESR1 in menopausal group. These results showed decreased LEPR and ERS1 genes methylations levels in post menopausal group. If replicated in larger study, these findings support that selected markers of epigenetic changes measured in WBC, such as LEPR and ERS1 genes methylations, may be potential biomarkers of menopausal state.
EVALUATION OF MATERNAL PLASMA TOTAL CELL FREE FETAL (cff) DNA IN PREECLAMPTIC PREGNANCIES
Y.S. El Kassar
1 , A.Z. Azzam 1 , F.M. Saleh 1 , S.R. Ahmed 1 , D.M. Hashad 5
Obstetrics, Gynecology Department, Faculty of Medicine, Alexandria, Egypt; 2 Clinical Pathology Department, Faculty of Medicine, Alexandria, Egypt
Background: Preeclampsia is best described as a pregnancy specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial dysfunction. It is also defined as a multisystemic pregnancy-specific disorder that is diagnosed by new onset hypertension and proteinuria after 20 weeks of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. That affects about 6-8% of all pregnancies. OBJECTIVES: The aim of the current study was to evaluate the probability of using maternal plasma total cell free DNA as a marker for future diagnosis of preeclamptic pregnancies. Methods: Fifty pregnant women >32 weeks gestation were recruited from El Shatby Maternity University Hospital, and were allocated into two groups, each (n=25). Preeclamptic group (groupI) and healthy normotensive pregnant women as a control group (group II). Every case was evaluated for maternal serum total cell free fetal DNA by using PCR technique. Results: The results of the present study revealed that: there was statistically significant difference between the two studied groups as regards maternal plasma total cff DNA. The mean value of maternal plasma total cffDNA was in preeclamptic women 2.486+ 0.8913 ng/μL and 1.058+ 0.2791 ng/μL in controls (P=0.000). The correlation between maternal plasma total DNA and systolic blood pressure, diastolic blood pressure and serum protein level was found in the form of positive association (P=0.034, 0.042 and 0.037) (r= 0.426, 0.422,and 0.419). Conclusions: Maternal plasma total cell free fetal DNA levels were elevated significantly in preeclamptic than normotensive women. There was a positive correlation between maternal plasma total cell free fetal DNA, blood pressure (systolic and diastolic) and protein level in urine.
INCREASED EXERCISE CAPACITY IS ASSOCIATED WITH LOWER MORTALITY IN HYPERTENSIVE MEN WITH TYPE 2 DIABETES MELLITUS
1,2 , A. Pittaras 1,2 , R. Kheirbek 1,2 , J.P. Kokkinos 1 , P. Kokkinos 1,2,3
Veterans Affairs Medical Center, Washington, District of Columbia, United States of America; 2 George Washington Medical Center, Washington, District of Columbia, United States of America; 3 Georgetown University School of Medicine, Washington, District of Columbia, United States of America
Introduction: Hypertension (HTN) and type 2 diabetes mellitus (DM) are major and independent risk factors and often coexist leading to an increased risk for mortality. Increase in physical activity is an integral part of both prevention and management of HTN and DM. However, the effects of physical activity in mortality risk reduction for hypertensive individuals with DM have not been thoroughly investigated. Method: A total of 2,379 men (mean age: 60±9.5) with HTN and type 2 DM underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved: The 1st quartile (≤5 METs) comprised the Least-Fit category (n=582). The 2nd quartile (5.1-7.0 METs) comprised the Low-Fit (n=806), in the 3rd quartile (7.1-8.9 METs) comprised the Moderate-Fit (n=514) and those in the 4th quartile (METs ≥9) comprised the High-Fit (n=477). All-cause mortality is reported within a follow-up period of 7.0±5.3 years. Results: There were 555 deaths, with 25.7 deaths per 1,000 person years of follow-up. After controlling for age, risk factors and medications, we observed an inverse and graded association between mortality risk and exercise capacity (p<0.001). When compared to the 1st quartile, the mortality risk declined progressively to 36%; 55% and 57% for those in the 2nd 3rd and the 4th quartiles, respectively. Conclusion: We found an independent inverse and graded association between fitness levels and mortality risk in hypertensive individuals with type 2 DM. Increased fitness levels confer a 36% to 57% reduction in mortality risk.
EFFICACY AND SAFETY OF CANAGLIFLOZIN IN SUBJECTS WITH TYPE 2 DIABETES ON METFORMIN AND PIOGLITAZONE
1 , R. Guthrie 2 , R. Goldenberg 3 , U. Vijapurkar 4 , J. Yee 4 , G. Meininger 4 , P. Stein 4
Institute for Clinical Research and Development, University of Mainz, Mainz, Germany; 2 The Ohio State University, Columbus, Ohio, United States of America; 3 LMC Endocrinology Centres, Thornhill, Ontario, Canada; 4 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
Canagliflozin (CANA), a novel inhibitor of sodium glucose co-transporter 2 (SGLT2), is being developed for the treatment of type 2 diabetes mellitus (T2DM). In this randomized, double-blind, placebo (PBO)-controlled Phase 3 study, subjects with T2DM inadequately controlled on metformin (MET) and pioglitazone (PIO) (N=342; mean age 57.4 y; A1C 7.9%; BMI 32.6 kg/m2) received CANA 100 or 300 mg or PBO. At 26 weeks, LS mean change in A1C was –0.89%, –1.03%, and –0.26% in the CANA 100 and 300 mg and PBO groups, respectively (P<0.001 both doses vs PBO), with 46.9%, 64.3%, and 32.5%, respectively, achieving A1C <7.0% (P<0.001 both doses vs PBO). Both CANA doses provided statistically significant reductions in FPG, body weight, and systolic blood pressure; increases in HDL-C, reductions in triglycerides, and an increase in LDL-C were also seen. Incidences of adverse events (AEs) (pooled CANA group 62.6%, PBO 66.1%), as well as of serious AEs, drug-related AEs, and AE-related discontinuations were similar among groups. Higher rates of AEs consistent with genital mycotic infections were seen with CANA vs PBO: 17.2% vs 5.1%, respectively (females) and 4.3% vs 0%, respectively (males). An increased incidence of AEs reflective of osmotic diuresis (pollakiuria [5.3%, 0.9%], polyuria [1.3%, 0%], or thirst [4.0%, 0%]) were observed with CANA, none serious or leading to discontinuation. Rates of urinary tract infections and hypoglycemia were low and similar across groups. In summary, CANA provided glycemic improvement, reduced body weight, and was well tolerated in subjects with T2DM inadequately controlled with MET and PIO.
MICROPARTICLES IN HYPERTENSIVE AND DIABETIC PATIENTS: EFFECTS OF HYPOLIPIDEMIC THERAPIES COMBINED OR NOT WITH CLOPIDOGREL
C.N. França, M.C.O. Izar, L.F.M. Pinheiro, J.B. do Amaral, L.L. do Amaral, S.P.M. Barbosa, F.A.H. Fonseca
Federal University of Sao Paulo, Sao Paulo, Brazil
Introduction: Atherosclerosis is an inflammatory disease complicated with thrombotic events related to endothelial dysfunction or apoptosis. Statins, ezetimibe and antiplatelet drugs are used in coronary artery disease patients and share common pathway in their metabolism. Microparticles are new biomarkers of cardiovascular disease and are related to the turnover of endothelial cells. Increased amount of microparticles has been reported in patients with uncontrolled risk factors. We examined the influence of two hypolipidemic therapies (simvastatin plus ezetimibe or rosuvastatin) combined or not with clopidogrel in the endothelial microparticles (EMP) and platelet microparticles (PMP) levels in diabetic and hypertensive patients. Methods: We enrolled forty stable coronary disease patients (79% males, median age of 58,66 years), with diabetes and hypertension, that were divided in two groups: treated with 40 mg simvastatin plus 10 mg ezetimibe or that received 80 mg rosuvastatin. We quantified by flow cytometry the baseline levels of EMP and PMP, after 1-wk of a daily dose of hypolipidemic therapies; after 1-wk of 300 mg clopidogrel (starting dose) followed by 75 mg/day plus one of the hypolipidemic therapies; and after 1-wk of clopidogrel alone (simvastatin plus ezetimibe or rosuvastatin were stopped for 1-wk). Results: In rosuvastatin group, there was a tendency to increase of EMP (p=0.05) and higher levels of PMP (p=0.01) after rosuvastatin withdrawal. In simvastatin plus ezetimibe group, there were no differences in all the points analyzed. Conclusion: short period of rosuvastatin discontinuation was associated with early increase in microparticles, showing potential harm among stable coronary disease patients.
HEALTH STATUS IN PEOPLE WITH TYPE 2 DIABETES IS SIGNIFICANTLY IMPROVED WITH INSULIN DEGLUDEC VS INSULIN GLARGINE
1 , L. Meneghini 2 , T.E. Christensen 3 , M.L. Wolden 3 , J. Jendle 4
University College London, London, United Kingdom; 2 University of Miami Miller School of Medicine, Miami, Florida, United States of America; 3 Novo Nordisk A/S, Søborg, Denmark; 4 Endocrine and Diabetes Center, Karlstad and University of Orebro, Orebro, Sweden
Aims: This meta-analysis of patient level data from three open-label, randomised trials of 26 or 52 weeks‟ duration compared the effect of ultra-long-acting insulin degludec (IDeg) and insulin glargine (IGlar) on health status in people with type 2 diabetes (T2D) starting basal–oral therapy. Design and methods: We assessed HbA1c, fasting plasma glucose (FPG), hypoglycaemia (PG<3.1 mmol/L) and health status using the Medical Outcomes Study Short Form 36 (SF-36). Insulin-naïve patients received IDeg (n=1290) or IGlar (n=632) once daily plus oral antidiabetic drugs. Statistical analysis was performed using a generalised linear model with treatment, trial, antidiabetic therapy at baseline, gender, region, age and relevant baseline values as explanatory variables. Results: At baseline, mean age was 58.6 y, HbA1c 67 mmol/mol (8.3%), FPG 9.4 mmol/L and BMI 30.0 kg/m<2>. In all three trials, IDeg was confirmed as non-inferior to IGlar based on HbA1c. FPG and confirmed overall and nocturnal (00:01–05:59 h) hypoglycaemia were all numerically or significantly lower with IDeg vs IGlar. For health status at study end, overall physical component score was significantly higher (improved) with IDeg vs IGlar (+0.66 [95%CI:0.04;1.28]), largely due to a difference (+1.10 [95%CI:0.22;1.98]) in the bodily pain domain score. In the mental domains, vitality was significantly higher with IDeg vs IGlar (+0.81 [95%CI:0.01;1.59]). The remaining SF-36 domains had scores in favour of IDeg, but were not significantly different between insulins. Conclusion: Compared with IGlar, IDeg leads to improvements in both mental and physical health status for people with T2D.
TREATING INSULIN RESISTANCE: CB1 RECEPTOR AS A POTENTIAL TARGET
D.T. Furuya, A.C. Poletto, H.S. Freitas, U.F. Machado
Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brasil
Evidences have suggested that the endocannabinoid system is overactive in obesity, resulting in enhanced endocannabinoid levels in both circulation and visceral adipose tissue. The cannabinoid CB1 receptor is expressed in skeletal muscle and adipose tissue besides the brain. Furthermore, some studies have demonstrated beneficial effects of the pharmacological treatment of obesity with CB1 antagonists on some components of metabolic syndrome. However, the mechanisms of such effect remain unknown. For this, the objective of the present study was to investigate the CB1 receptor modulation on the glucose transporter GLUT4 expression and the related mechanisms in obese mice treated with AM251, a high-selective CB1 receptor antagonist. Insulin sensitivity in vivo (by insulin tolerance test), GLUT4 mRNA (Real Time PCR) and protein (Western blotting) were assessed in 23-week old monosodium glutamate–induced obese mice untreated or treated with low doses of AM251 (0.01 mg/kg body weight) for 10 days. As expected, obese mice showed insulin resistance and reduced content of GLUT4 mRNA and protein in both skeletal muscle and adipose tissue. Interesting, AM251 treated-obese mice recovered insulin sensitivity in vivo and GLUT4 mRNA and protein content in skeletal muscle. However, treatment with CB1 antagonist did not affect GLUT4 mRNA and protein content in adipose tissue. In conclusion, the present data suggests that the skeletal muscle plays a key role in the amelioration of insulin resistance by CB1 receptor blockade. Funding by FAPESP (08/09194-4 and 12/04831-1)
SELF-MANAGEMENT COMPARISON OF ADULTS WITH TYPE 1 DIABETES IN LATIN AMERICA AND THE MIDDLE EAST: DATA FROM THE IDMPS
1 , P. Aschner 2 , J. Chan 3 , J.M. Chantelot 4 , E. Genestin 4 , M.P. Dain 4 , H. Ilkova 5 , F.J. Lavelle-González 6 , A. Ramachandran 7
Center of Experimental and Applied Endocrinology, La Plata National Scientific and Technical Research Council, La Plata National University, La Plata, Argentina; 2 Endocrinology Unit, Javeriana University, Bogotá, Colombia; 3 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; 4 Sanofi, Paris, France; 5 Department of Internal Medicine, Istanbul, Turkey; 6 Facultad de Medicina y Hospital Universitario, Monterrey, Mexico; 7 India Diabetes Research Foundation, Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
Aims: Self-management (SM) is an important aspect of diabetes care and is recommended in order to achieve glycaemic control. The aim of the International Diabetes Management Practices Survey (IDMPS) is to document the current quality of care provided to people with type 1 or 2 diabetes mellitus (T1DM or T2DM) and to identify T1DM patient profiles for SM. Methods: The IDMPS is an ongoing, 5-year, multi-national, observational study in patients with T1DM and T2DM in Latin America (LA) and the Middle East (ME). Data were collected over a period of 4 years in LA (2693 patients) and 3 years in the ME (1316 patients) and pooled. SM was defined as both self-monitoring blood glucose (SMBG) and insulin self-adjustment (ISA) performance. Patient profiles were determined by logistic regression analysis. Results: SM performance, frequency of SMBG and ISA were greater in LA than in the ME (58.1 vs 51.3%; 82.3 vs 74.2%; 62.9 vs 61.2%, respectively). In both LA and the ME, SM was significantly (P < 0.05) associated with age (< 40 vs > 65 years), university education, diabetes education, time since diagnosis (for 5-year changes), insulin pen (vs vials-syringes use), basal-prandial regimen (vs both basal regimen and other regimens). In addition, in LA SM was significantly (P < 0.05) associated with health insurance and patient recruitment by specialists (OR = 1.6). In both regions, SM was associated with better glycaemic control. Conclusion: A specific effort should be made to empower adults with T1DM to improve quality of care and outcomes.
THE VASCULAR STIFFNESS IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS
1 , C. Nica 1 , C.V. Ion 1 , S.V. Fica 1,2
Elias Emergency University Hospital, Bucharest, Romania; 2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Background and aim: Increased arterial stiffness is an independent predictor of cardiovascular risk. The aim of this study was to assess the augmentation index (AIX), showing the vascular extensibility and to investigate the influence of hypertension (HT) in patients with type 2 diabetes mellitus (T2DM). Material and methods: 109 T2DM patients (male/female 54/55) mean age 59.72 ± 5 years underwent evaluation of AIX using a Vascular Screening Device Vasera VS-1000. The AIX expresses the ratio of percussion wave generated along with a pressure increase of aorta to the tidal wave at the systole in carotid and brachial pulse wave. All diabetic patients were divided into two groups: one with normal tension (NTD) and another with hypertension (HTD). In 72 apparently healthy subjects we also measured the AIX and we found 20 patients only with HT. Results: AIX in diabetic patients was significantly higher than in subjects with HT alone (1.1 vs. 0.7, p = 0.02) and in apparently healthy individuals (1.1 vs.0.9, p =0.001). Among the T2DM patients AIX of HTD was significantly higher than in NTD group (1.7 vs. 1.02 , p = 0.04). The AIX of T2DM patients was significantly correlated with age (r =0.43, p = 0.03) and with pulse pressure (r = 0.38, p = 0.03), not also with HbA1c (metabolic control). Conclusion: The arterial stiffness was higher in diabetic patients and it was significantly enhanced when HT merges in T2DM. The AIX measurement is useful for detecting cardiovascular risk.
CORRELATION BETWEEN TISSUE DOPPLER IMAGING AND PLASMA LEVEL OF NT PRO BNP IN ASSESSMENT OF LEFT VENTRICULAR DIASTOLIC FUNCTION IN ASYMPTOMATIC HYPERTENSIVE PATIENTS
1 , W.A. El Aroussy 2 , M.A. Shalaby 1 , H.A. Negm 1 , S.A. Omar 1
Research Institute of Ophthalmology, Cardiovascular Unit, Ministry of Higher Education, Egypt; 2 Cardiology Department, Faculty of Medicine, Cairo University , Egypt
Tissue Doppler imaging of the mitral annulus may predict the diastolic filling of left ventricle. Objectives: we investigated the pattern of diastolic function in a subset of hypertensive patients and evaluated the correlation between mitral annular TDI velocities & plasma level of NT pro BNP and its predictive cutoff value to diagnose LV diastolic dysfunction. Methods: After full clinical examination, we prospectively measured plasma level of NT pro BNP, assessed LVH by both ECG, Echo. we measured LV EF, Left atrial diameter , left venricular geometry and assessed LV diastolic function by both mitral flow pattern & mitral annular TDI parameters, in 40 Asymptomatic patients with normal EF (more than 55%) and 20 healthy control subjects. Results: We found that Ea velocities were decreased in hypertensive group with diastolic dysfunction. Moreover, E/Ea ratio was higher in hypertensive group(p=0.04) .the E/Ea was significantly& directly correlated with the level of NT pro BNP(r=0.41,P=0.008). The powerful predictors of NT pro BNP level in hypertensive patients with diastolic dysfunction were E/Ea(r=0.41,P=0.008), LVMI(r=0.41,P=0.015) and duration of hypertension(r=0.6,P=0.0001). Moreover, the powerful predictor of concentric LVH geometry is the duration of the hypertension(r=0.42, P=0.01). The cutoff point of NT pro BNP plasma level to detect diastolic dysfunction in asymptomatic hypertensive patient were 40.7 pg/ dl (sensitivity 95% and specificity 84%). Conclusion: Combination of tissue Doppler parameter and NT pro BNP plasma level offers a new strategy of risk stratification in hypertension. NT pro BNP is a promising marker to detect the subclinical state of heart failure with normal ejection fraction especially in hypertensive patient with diastolic dysfunction.
NUTRITIONAL STATUS AND CARDIOVASCULAR RISK FACTORS AMONG KHISÊDJÊ BRAZILIANS INDIGENOUS: A CROSS-SECTIONAL STUDY
1 , L. Massuccheti 1 , P.O. Paiva 1 , K.M. Santos 1 , D.A. Rodrigues 1 , M.L.S. Tsutsui 1 , L. Mondini 2
São Paulo Federal University, São Paulo, Brazil; 2 Instituto de Economia Agrícola do Estado de São Paulo, São Paulo, Brazil
Brazilians Indigenous people go through a complex process of epidemiological transition, which persist infectious and parasitic diseases along with significant increase of chronic diseases. Among the Indigenous subjects that live in the Xingu Indigenous Park (XIP, Mato Grosso, Brazil), the prevalence of overweight, central obesity and dyslipidemia are ≥ 60% (higher than the Brazilian non-indigenous population). The Khisêdjê are a Ge-speaking people living in the XIP. The contact intensification with the non-indigenous society and the increased number of subjects with professional activity suggested that this situation has deteriorated. In this context, we investigated the existence of associations between nutritional status, defined by body mass index (BMI, kg/m2), anthropometric variables, biochemical profile and the Framingham cardiovascular risk (CVR). This cross-sectional study included 173 Khisêdjê (101 men and 72 women) aged ≥ 20 years (91% of total eligible). The data collection was performed at the main village (Ngojwere) between 2010 and 2011. We used chi-square test (proportions) and Anova (means) in the data analysis. The prevalence of overweight (BMI ≥ 25 kg/m2) was higher among men than women (57.4% vs. 37.5%, p = 0.026), regardless of age. Similarly, the CVR was also higher among men (6.3 vs. 2.4, p <0.001). In both genders the overweight was positively associated with waist circumference and leptin, and negatively, with reactance, resistance and adiponectin (among men). No relationship was observed between BMI, C-reactive protein and CVR. These results suggest that BMI does not indicate CVR among this Brazilians Indigenous.
RELATIONSHIP BETWEEN BODY FAT RATIO AND MORTALITY
Kangwon National University, Chuncheon, Korea
Background: Body mass index(BMI) is widely used for diagnosis of obesity but it is not an accurate indicator for adiposity.
The relationship between body fat ratio(BFR) and mortality remains controversial. The objective of this study was to evaluate the relationship between BFR and all-cause mortality in Korean population. Methods: Authors examined the association between body fat ratio and mortality among 8487 women and 8436 men aged 40-85 years who visited health promotion center from 1995 to 1999. Additionally, BMI, blood pressure, glucose, lipid, CRP, smoking status, alcohol consumption, regular exercise, sleeping time, marriage status, education duration, and income were examined. BFR was estimated by bioelectric impedance analysis. Results: There were 601 deaths over a median follow-up period of 11.2 years except the first 2 years. BFR shows a significant linear association with mortality and this trend tends to be more distinguished in women and cardiovascular disease. These findings persisted after adjusted for BMI, blood pressure, glucose and other potential confounders. Risk of death was highest in low BMI and high BFR group and lowest in high BMI and low BFR group. Conclusion: The finding that BFR remained strongly and directly associated with all-cause mortality and cardiovascular mortality when adjusted for BMI, and persons with a normal BMI but a high BFR had a higher mortality risk suggest that increased BFR should be considered a risk factor for mortality, in addition to BMI in especially relatively thin Asian population.
METABOLIC SYNDROME AND INSULIN RESISTANCE IN ADULT PATIENTS UNDERGOING DIET-INDUCED WEIGHT LOSS PROGRAM
L.F. Grandisoli, N.R.T. Damasceno, E.K.N. Aguchiku
University of Sao Paulo's Hospital, Sao Paulo, Brazil
Background: Obese patients are likely to have metabolic dysfunctions and a wide variety of diseases, most of them related to metabolic syndrome (MetS), resulting in an increased risk of cardiovascular morbimortality. The goal of this study was to assess the clinical profile of overweight and obese adults undergoing diet-induced weight loss treatment at University of São Paulo´s Hospital, Brazil. Methods: International Diabetes Federation (IDF) criteria and HOMA-IR were respectively used to diagnose MetS and insulin resistance in fifty-four patients. Mann-Whitney and Spearman correlation tests were used (SPSS 17.0). Results: MetS was diagnosed in 53.7% of the patients, mostly in men (71.4%) than in women (47.5%), and in obese (75.0%) than in overweight patients (11.1%). The most prevalent component was high waist circumference (WC), present in 100% of patients with MetS, followed by hypertension (79.3%), high triglycerides (75.9%), high fasting glucose/DM (62.1%), and low HDL (51.7%). Patients with MetS had significantly higher weight (p<0.001), BMI (p<0.001), WC (p<0.001), blood pressure (p<0.001), triglycerides (p<0.001), total cholesterol (p=0.031), fasting glucose (p<0.001), fasting insulin (p=0.023) and HOMA-IR (p=0.002). Regardless of MetS‟s diagnosis, there was a significant correlation between HOMA-IR and weight (r=0.531, p<0.001), BMI (r=0.539, p<0.001), WC (r=0.446, p=0.001), systolic pressure (r=0.369, p=0,006) and diastolic pressure (r=0.372, p=0.006). Conclusion: The prevalence of MetS is high in overweight and obese patients. Insulin resistance was positively correlated with anthropometric parameters and blood pressure regardless of MetS‟s presence, reinforcing the importance of monitoring that parameter in overweight and obese patients.
EXPERIMENTAL MODEL OF DIABETES MELLITUS TYPE 2 AS A TOOL IN MONITORING CHRONIC STUDIES
1 , I. Leal-Anguiano 1 , S.G. Huerta-Olvera 2 , A.O. Vázquez-Alvarez 2 , A.M. Salazar-Montes 3 , A. Miranda-Díaz 2 , E.G. Cardona-Muñoz 2 , A.R. Rincón-Sánchez 3 , M.C. Islas-Carbajal 2
Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara; Guadalajara Jalisco, México; 2 Unidad de Investigación Cardiovascular, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco, México; 3 Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco, México
Introduction: Diabetes Mellitus (DM) induces several complications that represent the principal cause of mobility and mortality in diabetic population. Animal models for type 2 diabetes mellitus including genetic and chemically induced, none of them simulate human type 2 DM and chronic complications. Objectives: The aim of the study was development an animal model of type 2 diabetes in order to resemble as much as possible the events that occur in type 2 diabetic patients and that may be useful for chronic studies. Methods: Hyperglycemia was induced in male Wistar rats (150-200 g) by 5 intraperitoneal injections of low doses of streptozotocin (20 mg/kg) in addition to a high fat diet (HFCD). The evaluation was done by metabolic, blood glucose measures and pancreatic histological studies. They were sacrificed at different times until 25 weeks. Results: Experimental diabetes using low doses of streptozotocin in addition to a high fat diet caused stable hyperglycemia, without their gradual recovery to normoglycemia. The use of insulin therapy to sustain life was not necessary suggesting that doses calculated to cause a partial destruction of β cell mass in addition to a high fat diet was appropriated. We found similarities with the human condition in our model, which presented moderate obesity, polydipsia, polyphagia, polyuria, and stable hyperglycemia without a tendency to cause ketosis or deterioration into type 1 diabetes mellitus. Conclusion: This model could be useful to investigate mechanisms related to this important chronic macrovascular complication of diabetes and useful to research in order to find new therapies.
DOES PSYCHOLOGICAL INTERVENTION AFFECT WEIGHT LOSS IN OBESE PATIENTS ATTENDING A WEIGHT MANAGEMENT CLINIC?
N. Haboubi, C. Bracchi, J. Gray, S. Jones, A. Weaver, J. Reynolds, G. Goldings
Aneurin Bevan Specialist Weight Management Clinic, Ebbw Vale, NP23 3XE, United Kingdom
Introduction: Obesity is strongly linked to certain eating-disorders. Published works suggest that patients who eat in response to emotion tend to lose less weight in weight loss programs. Objective: To determine whether psychological intervention improved weight loss in patients attending a weight management clinic. Method: Twenty-four patients were allocated to the intervention group (patients who had psychological problems with a mood score of over 11), and twenty-three to the control group (patients without psychological problems). The Student‟s t-test, chi-squared test and Spearman‟s correlation coefficient were used to analyze the data. Results: There was no significant difference between weight loss or weight loss maintenance between the intervention and control groups with p values of 0.8127 for weight loss after six months, 0.5285 for weight loss after one year and 0.3683 with regards to maintenance of weight loss. In the intervention group alone, there was found to be a significantly positive correlation between weight loss and mood score (measure of psychological problems), and significantly negative correlations between weight loss and BMI at baseline, and weight loss and number of consultations with the psychologist, with p values of 0.0036, 0.0065 and 0.0124 respectively. Conclusion: The presence of a psychologist in a multi-disciplinary weight management clinic is essential for achieving comparable weight loss and weight loss maintenance between patients who have psychological problems and patients who do not.
THE SODIUM GLUCOSE COTRANSPORTER-2 (SGLT-2) INHIBITOR EMPAGLIFLOZIN LOWERS BLOOD PRESSURE INDEPENDENT OF WEIGHT OR HBA1C CHANGES
1 , H.J.L. Heerspink 2 , E. Pfarr 1 , S. Lund 1 , L. Ley 1 , U.C. Broedl 1 , H.J. Woerle 1
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 2 University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Objective: To evaluate effects of empagliflozin on systolic and diastolic blood pressure (SBP and DBP) and correlations between changes in weight or HbA1c from a pooled analysis of data from two randomized controlled 12-week phase 2b trials. Methods: Data were pooled from patients on empagliflozin 10mg (N=152), empagliflozin 25mg (N=152) and placebo (N=153). Changes from baseline in HbA1c, weight, BP were assessed and Pearson correlation coefficients calculated. Results: Baseline mean (SD) SBP and DBP (mmHg) ranged from 131.3(13.8)–134.3(15.9) and 79.1(9.1)–80.9(9.2), respectively. Mean [SE] changes from baseline in SBP (mmHg) in patients receiving empagliflozin 10mg, 25mg and placebo were -3.8[1.0], -4.5[1.0], and -1.2[1.0], respectively (p<0.05 versus placebo for each dose) and appeared larger in patients with baseline SBP >140mmHg (-17.0[2.6], -13.4[2.3], -10.4[2.4], respectively). Mean changes from baseline in DBP with empagliflozin 10mg, 25mg and placebo were -2.3[0.6], -2.7[0.6], and -1.8[0.6], respectively (p=NS for each dose). Correlation coefficients between change in weight and change in SBP with empagliflozin 10mg, 25mg and placebo were 0.10, 0.04 and 0.12 and between change in HbA1c and change in SBP were -0.09, -0.02 and 0.11, respectively (p>0.14, for each). The number of patients with AEs was comparable among treatment groups (34.2% [empagliflozin 10mg], 31.6% [empagliflozin 25mg] and 34.6% [placebo]). Conclusion: Empagliflozin provided statistically significant, clinically meaningful reductions in SBP, which seemed more pronounced when baseline SBP>140mmHg. BP changes were not correlated with changes in weight or HbA1c. Empagliflozin was generally well tolerated. These data were presented at EASD 2012. Funded by Boehringer Ingelheim.
IMPACT OF BARIATRIC SURGERY ON PREGNANCY COMPLICATIONS- ABOUT 2 CASE CONTROL STUDIES
1 , E.B. Boudier 2 , M.V. Vix 2 , P.K. Keller 3 , I.N. Nisand 2
Centre Hospitalier de Valence , Valence , France; 2 Centre Hospitalo Universitaire de Strasbourg, Strasbourg , France; 3 Centre Hospitalier de Colmar, Colmar, France
Morbid obesity is steadily increasing and affects mainly the age group between 25 and 34 years, mostly women of childbearing age. In terms of obstetrics, obesity is a significant risk factor for maternal and fetal morbidity. Objectives: To determine the impact of bariatric surgery on obstetrical maternal-fetal issues and study the impact of the delay between the surgery and early pregnancy. Patients and Methods: 2 studies : the first type case-control pregnancies compared 66 cases who benefited from bariatric surgery in the Alsace region in 124 pregnancies (control 1) in morbidly obese and having given birth University Hospitals of Strasbourg. The second type study with longitudinal pre-post retrospective collection of data compared the pregnancies of 66 patients who underwent bariatric surgery in 34 pregnancies (control 2) of these patients before the act of bariatric surgery. Results: Bariatric surgery provides obstetrical benefits. After multivariate logistic regression analysis, there was a significant decrease in the rate of preeclampsia was OR = 0.16 [0.03 to 0.94] compared with controls 1 and a rate of gestational diabetes OR a = 0.23 [ 0.08 to 0.72] compared with controls 2. Among patients operated, there were fewer excessive weight gain during pregnancy (p = 0.0023) compared with controls 2. The rate of emergency caesarean section tended to be lower (p = 0.06) compared with controls 2. Conclusion: The current data suggest a decrease in the rate of gestational diabetes and preeclampsia in pregnancies following bariatric surgery. Neonatal complications such as macrosomia appear less frequent in these patients.
IRON DEFICIT IN TYPE 2 NON DYALISED DIABETIC PATIENTS
1 , C. Bondor 2 , I.A. Veresiu 2 , M. Coca 1
Clinical Centre for Diabetes, Nutrition and Metabolic Diseases Cluj-Napoca, Romania; 2 University of Medicine and Pharmacy Cluj-Napoca, Romania
Aim: To assess the frequency of iron deficit in type 2 non dialysed diabetes patients according to the degree of chronic complications, a first evaluation of the kind in this country. Methods: 400 caucasian type 2 diabetes patients with no known pathology that interferes with iron metabolism, in whom specific parameters: iron, erythropoietin, ferritin, transferin, Creactiveprotein(CRP) were determined. Results: 61% of the group were males, mean age was 62.37±7.23 years, diabetes duration was 11.67± 6.48 years. Iron deficit was found in 78.8 %, absolute iron deficit(AID) in 46.5%, functional iron deficit (FID) in 32.3%, iron deficit anemia (IDA) was present in 18.5%. AID was higher in women than men 59% vs 38,5%, its frequency was higher 44,7% at KDOQI 1 than 26.7% in the KDOQI 4 and 5 stages(p=0.040); FID increased from 29,1% to 46,7%(p=0.48); iron deficit anemia increased from 10.7% to 66.7%(p<0.0001) respectively. Functional erythropoietin deficit increased from 16% to 66.7% p=0.00001 KDOQi 1 to 4. In logistical regression models AID was associated with female sex, OR 1.954 95% CI 1.23-3.12 p=0.005, FID was associated with autonomic neuropathy: OR 2.96 CI 1.27-6.42 p=0.001, CRP: OR=1.03 95%CI(1.01-1.05), proliferative retinopathy: OR=4.849, 95%CI(1.499-15.686), p=0.008, IDA with KDOQI stage: OR=1.6, 95%CI(1.055-2.426) p=0.002. Conclusions; Iron deficit and anemia in nondialysed type 2 diabetic patients is a frequent finding, increasing severity of renal dysfunction is the main factor leading to iron deficit, followed by presence of autonomic neuropathy and severe retinopathy, properly modulated treatment is still controversial and remains to be assessed.
ANALYSIS OF RESULTS OVER TIME IN PREVENTIVE INTERVENTION FOR METABOLIC SYNDROME
H. Imai, H. Nakao, F. Sata
National Institute of Public Health, Wako, Japan
Objective: The Specific Health Examination and Specific Health Guidance Program directed at metabolic syndrome was started in 2008 as a national preventive measure for lifestyle-related diseases in Japan. Fifty two million people nationwide are eligible for examination under this program. Health guidance intervention targeting people with obesity, hypertension, hyperglycemia has been required in about four million of these individuals. The aim of the study is to analyze the effect over time in the specific health guidance in patients in the Tokyo area. Method: Based on data in 2008, 2009, and 2010 in individuals eligible for specific health guidance in the area, the results of that health guidance intervention were analyzed by comparing people who did and did not receive such intervention. Results: 58,898 people between 40 and 73 years of age in the area received specific health examinations, and 15,004 of them were eligible for specific health guidance. 2,045 of these people received health guidance intervention, whereas 12,959 did not. Analysis of changes in 2008, 2009, and 2010 revealed the average in systolic blood pressure revealed blood pressure levels (mmHg) of 134.5, 132.2, and 131.4, respectively, in males, and 138.2, 133.1, and 133.9, respectively, in females. In individuals receiving no intervention, the blood pressure levels were 134.8, 131.9, and 132.1, respectively, in males, and were 138.1, 133.8, and 133.9, respectively, in females. Discussion: The program was initiated only a little over 4 years ago, and to assess the effects of this preventive measure over the long term will be necessary.
LONG ACTING INSULIN ANALOGS EXPOSURE AND CANCER MORTALITY
1 , C. Guja 1 , C. Ionescu-Tirgoviste 1 , S. Fica 2 , S. Martin 2 , S. Sabau 3 , C. Tiu 4
I. Pavel Outpatient Clinic, Bucharest, Romania; 2 Elias Hospital, Endocrinology and Diabetes, Bucharest, Romania; 3 Tokai University, Statistics, Sapporo, Japan; 4 University Hospital, Neurology, Bucharest, Romania
Aim: To investigate long acting insulin analogs exposure effects on overall and site-specific cancer mortality. Methods: All consecutive oral-treated diabetes patients in a major urban area (65117 cases) were followed for first insulin prescription during 2001-2008. Inception date was six months after first insulin prescription. Patients aged 40-79 years (8424 cases, 42.9% males, mean age 62.2±9.4 years) were followed-up for death until 12/31/2011 (100% cover-up, 44588 person-years). Competing risks regression analysis used exposure time, daily dose and cumulative dose as time-dependent variables (daily updates). Each model included data for sex, baseline age, regular insulin, rapid analogs, long/intermediate human insulin (LIH-insulin), human mixtures, analog mixtures, glargine, detemir, metformin, glibenclamide, gliclazide, glipizide, gliquidone, and glimepiride. Results: There were 2246 deaths (50.4/1000 person-years), including 383 cancer deaths (155 colorectal, 65 lung, 62 breast, 53 pancreatic, 14 prostate, 34 others). Competing risks regression hazards for one year exposure were: glargine 0.93 (95%CI 0.82-1.05), detemir 0.94 (95%CI 0.78-1.12), LIH-insulin 0.97 (95%CI 0.86-1.09), metformin 0.91 (95%CI 0.83-0.99, p=0.036). Daily-dose hazards (10IU/day): glargine 0.96 (95%CI 0.93-1.01), detemir 0.97 (95%CI 0.93-1.02), LIH-insulin 1.01 (95%CI 0.96-1.04). Cumulative dose hazards (every 1000IU): glargine 0.34 (95%CI 0.14-0.83, p=0.018), detemir 0.21 (95%CI 0.03-1.34), LIH-insulin 0.75 (95%CI 0.34-1.65). Male gender and higher age were significant risk factors in all models. Glargine, detemir, and LIH-insulin exposure had no effect on site-specific cancer mortality. Conclusions: In incident users of insulin, exposure to long acting analogue/human insulin was not associated with increased overall and site-specific cancer mortality. Glargine had a beneficial effect in cumulative dose analysis.
THE EFFECT OF FREQUENCY OF MEALS ON BODY WEIGHT, HBA1C AND RESTING ENERGY EXPENDITURE IN PATIENTS WITH TYPE 2 DIABETES
1 , L. Belinova 1 , M. Hill 2 , T. Pelikanova 1
Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2 Institute of Endocrinology, Prague, Czech Republic
Introduction: Caloric restriction is crucial in the treatment of type 2 diabetes (T2D) typically (but not necessarily) apportioned into five or six small meals during the day. The aim of our study was to compare the effect of six vs. two meals a day with the same caloric restriction on body weight, HbA1c and resting energy expenditure in subjects with T2D.
Methods: In a randomized, crossover study, we assigned 54 patients with T2D to follow two regimens of a hypocaloric diet (-500 kcal/day), each for 12 weeks: six meals a day (A), and two meals a day (B). The diet in both regimens had the same macronutrient and energy content. At weeks 0, 12 and 24 we measured weight and HbA1c and performed indirect calorimetry. For statistical analysis, 2x2 crossover ANOVA was used. Results: Body weight decreased in both regimens (p<0.001), more in B (-2.3; 95% CI -2.7 to -2.0 kg in A vs. -3.7; 95% CI -4.1 to -3.4 kg in B; p<0.001). Hb1Ac decreased in both regimens (p<0.001) with a trend toward a greater decrease in B (-0.23; 95% CI -0.27 to -0.19 % in A vs. -0.25; 95% CI -0.29 to -0.20 % in B; p=0.08). Respiratory quotient increased in both regimens (p<0.01). REE decreased in both regimens (p<0.001) with a trend toward a greater decrease in A. Conclusions: Our data suggest that it may be more beneficial to apportion a diet into fewer larger meals than into smaller ones during the day for patients with T2D.
GAPP2™ SURVEY: GERMAN T2DM PATIENTS ARE CONCERNED ABOUT HYPOS AND DOSING IRREGULARITIES WITH INSULIN
1 , M. Brod 2 , U. Steiner 3 , M. Peyrot 4
Diabetologische Schwerpunktpraxis, Frankfurt, Germany; 2 The Brod Group, Mill Valley, California, United States of America; 3 Novo Nordisk, Mainz, Germany; 4 Loyola University Maryland, Baltimore, Maryland, United States of America
Aims: In Germany, optimising glucose control in type 2 diabetes (T2DM) is a key treatment outcome, and insulin analogue (IA) use is common. However little is known about IA dosing and self-treated hypoglycaemia (hypos) in everyday practice. Methodology: Data from an international internet survey (GAPP2) on basal insulin (BI) administration and hypos from 302 T2DM German (GE) patients using IA and 209 prescribers (reporting IA patients) are compared with 2740 T2DM patients using IA and 1013 prescribers from other GAPP2 countries (G2=US, Canada, Japan, UK, Denmark). Results: Significantly more GE than G2 patients said their T2DM was well controlled (56% vs 32%), but GE patients had missed (19%) mis-timed (25%) and reduced (15%) BI doses in the last 30 days. Significantly less GE patients reported guilt about missing BI doses (27% vs 38%), despite significantly more reporting awareness of the negative long-term health impact (72% vs 62%). 31% of GE patients (vs 36% G2) reported hypos in the last 30 days. Significantly more GE patients worried about hypos (nocturnal 55% vs 40% / diurnal 33% vs 22%). Significantly more GE patients let their blood glucose go high to reduce nocturnal hypo risk (24% vs 13%) and significantly more GE prescribers reported starting patients on a lower than recommended BI doses because of hypo risk (71% vs 53%). Conclusions: More GE T2DM IA patients are worried about hypos and less worried about dosing irregularities. GE prescribers should be aware of this perception mismatch to effectively address these issues during consultations.
ANTI-HYPERTENSIVE TREATMENT INCREASES CAPILLARY DENSITY IN PATIENTS WITH STAGE I AND II HYPERTENSION
1 , A.F. Sanjuliani 1 , M.B. Gomes 2 , E.V. Tibiriçá 3
Rio de Janeiro State University, Clinex, Rio de Janeiro, Brazil; 2 Rio de Janeiro State University, Diabetes Unit, Rio de Janeiro, Brazil; 3 Oswaldo Cruz Institute, Rio de Janeiro, Brazil
Background: Capillary rarefaction and reduced capillary recruitment are hallmarks of arterial hypertension and reflect systemic microvascular endothelial dysfunction. Objectives: To assess the effects of a six-month treatment period with a beta-blocker or an antagonist of the AT1 receptor on systemic microvascular density of hypertensive patients. Methods: Prospective, randomized, open-label study, blind endpoint assessment. Newly diagnosed stage I or II hypertensives were treated either with metoprolol (METO, 100 mg/day, n=20) or olmesartan medoxomil (OLME, 40 mg/day, n=24) with hydrochlorotiazide added if needed. Twenty normotensive subjects matched for age, sex and body mass index were used as controls. Skin capillary density was evaluated using videocapillaroscopy before and during post-occlusive reactive hyperemia (PORH). Values were expressed as mean±SD. Results: The study comprised forty-four patients (23 men) aged 46.7±1.3 years. Mean systolic and diastolic blood pressure decreased to the same extent in both groups. Capillary density (CD, capillaries/mm2) was significantly lower in the pool of patients in resting conditions (71.3±1.5) and during PORH (71.7±1.5) when compared to controls (80.6±1.8, P<0.001 and 79.5±2.6, P<0.05, respectively), and increased to 75.4±1.1 (P<0.001) and 76.8±1.1 (P<0.05) after treatment, respectively. Basal CD increased after METO treatment (from 70.0±1.9 to 75.9±1.7; P<0.05) but not after OLME treatment (from from 72.3±2.2 to 75.0±1.5; P=0.17); CD during PORH also increased after METO treatment (from 69.8±1.8 to 76.3±1.7; P<0.001) but not after OLME treatment (from 73.3±2.4 to 77.2±1.6; P=0.05). Conclusions: Anti-hypertensive treatment reverses capillary
rarefaction and increases capillary recruitment, which is consistent with improved microvascular endothelial function.
PREVALENCE OF OBESITY AMONG ARAB WOMEN IN NAZARETH
M. Kandalaft Khoury
1 , O. Mordechai 2 , N. Shehadeh 2
Clalit Medical Services, Nazareth, Israel; 2 Diabetes Clinic, Mayer Rambam Center, Haifa, Israel
Background: In Israel, at least one third of Arabs are obese. Arab women have particularly very high rates of obesity compared to Jewish women in age group above 40 years. Objectives: The objective of this study was to determine the prevalence and factors associated with obesity among Arab woman in Nazareth. Methods: We randomly recruited 300 women attending a primary health care clinic. All subjects were interviewed in person using a structured questionnaire. Results: We have totally 300 women, mean BMI was 30.3, 45% were obese and 16.8% had overweight. The following table demonstrates the relationship between several risk factors and obesity. The prevalence of overweigh and obesity among Arab woman over 40 years of age who attend primary health clinic was 74%. Obesity was higher in woman with multiparity (fig 1), and those with a less school years. Figure 1: The correlation between number of children and mean BMI Conclusion: Arab woman in Nazareth have a high prevalence of obesity which may be attributed to social and life style characteristics.
OBESITY IN KUWAIT: AN EPIDEMIOLOGIC REVIEW
S. Karageorgi, O. Alsmadi
Dasman Diabetes Institute, Kuwait City, Kuwait
Introduction: Overweight and obesity prevalence rates have been increasing worldwide. In affluent countries such as Kuwait obesity is a major health issue. In this systematic review, we summarize epidemiologic data from studies conducted on the prevalence, trends and risk factors of obesity in Kuwait. Methods: The PubMed database was searched for relevant studies using the MeSH terms combination overweight OR obesity AND adults AND Kuwait. Publications were selected based on title and abstract review, followed by full text review. Results: One hundred and two articles were identified in PubMed, and 58 articles remained after exclusion based on title and abstract review. Of the 58 articles, 20 articles have been reviewed so far. The studies reviewed were published in recent years (1998-2007) and were all cross-sectional. Fifty-five percent of the studies examined prevalence and risk factors, 33% prevalence rates only, and 11% time trends. BMI was measured in all studies and the sample size ranged from 296 to 7,609 individuals. The prevalence of obesity ranged from 9% to 57% and was higher in women than men. Studies that examined trends showed an increase in obesity prevalence rates by 10% between 1980 and 1993. The risk factors investigated in these studies included cardiovascular and sociocultural risk factors that were crudely assessed. Conclusion: This is the first review to summarize obesity epidemiologic findings in Kuwait. Studies report high obesity prevalence rates. There is a need for further studies to carry out comprehensive investigations of the factors contributing to obesity epidemic in Kuwait.
PATIENTS’ AND HEALTHCARE PROFESSIONALS’ PERSPECTIVE OF TYPE 2 DIABETES MELLITUS MANAGEMENT: A FOCUS-GROUP STUDY
1 , M. Mazurkiewicz 2 , D. Kurpas 2
First Department of Family Medicine, Medical University of Lodz, Poland; 2 2Family Medicine Department, Medical University of Wroclaw, Poland
Background: Therapy of type 2 diabetes mellitus (DM2) is a challenge not only for doctors but also for the patient themselves. Objective: The aim of this study was to identify major problems associated with DM2 therapy in Poland, both from the patients‟, and from healthcare professionals‟ (HCP) perspective. Design: We conducted a qualitative study that was based on two patient focus groups and three HCPs group using a structured discussion guide to explore problems related to DM2 management. Participants: We enrolled 19 DM2 primary care patients in two urban locations (Lodz and Wroclaw), as well as 15 HCPs (in Wroclaw). Measures: We performed content analysis of verbatim focus-group transcripts to assess themes within each problem domain. Results: Patients identified many problems that they experienced due to DM2 self management, including concerns about diet, drugs, and adverse effects. On the other hand, patients admitted that well-design telemedicine system could reduce their stress, because they would not feel alone with their problems on the daily basis. HCPs pointed at the decline of patient compliance to their advices with time. They also believed that telemedicine system could be of high usefulness in DM2 patients, and particularly among young, active people who are up-to-date with new technologies. Such a system could collect structured data which are crucial for DM2 management by HCPs. Conclusion: Many patients experience several problems connected with daily management of their DM2. A telemedicine system that accompanies these patients could be of great help for both patients, and HCPs.
ASSOCIATION OF VDR GENE APAI POLYMORPHISM WITH SERUM LIPOPROTEIN LEVEL IN REPRODUCTIVE AGE WOMEN
1,2 , E.V. Tsvetkova 1 , A. Kostareva 1 , A. Klushina 1 , O.D. Belyaeva 1,2 , E.P. Micheea 2 , A.V. Berezina 1,2 , E.N. Grineva 1
V.A. Almazov Federal Centre of Heart, Blood and Endocrinology, Saint Petersburg, Russia; 2 Saint Petersburg State Medical University n.a. I.P. Pavlov, Saint Petersburg, Russia
It is well known, that Vitamin D deficiency is associated with increased risk of metabolic diseases including obesity, diabetes type 2, hypertension, dyslipidemia. Not only Vitamin D deficiency could play an important role in their pathogenesis, but also VDR gene status. Aim: To study the association between VDR gene ApaI polymorphism with serum Vitamin D and lipoproteins levels. Materials and methods: We studied 340 healthy women who signed informed consent; aged 28 to 55 years (mean 44.2±0.3). Serum 25(OH)D concentration was determined by ELISA using comercially kits (Immunodiagnostic System Ltd, UK). Normal level was considered more than 75 nmol/L. The level of serum lipoproteins was measured on COBAS INTEGRO 400/700/800 analyzer, using standard reagents company Roche (Germany). VDR ApaI genotype was determined by PCR-based method followed by restriction analysis. Results: Vitamin D insufficiency and deficiency was revealed in 86.8% of healthy women, only 13.2% of them had normal 25(OH)D level. Hypertriglyceridemia and/or increased low density lipoprotein (LDL) level was identified in 40% (136 persons). VDR gene Apa I polymorphism was identified in all participants, the frequency of A-allele was 0.52, a-allele–0.48. The frequencies of AA, Aa and aa genotypes were 23.8 %, 55.8% and 20.6% respectively. We did not find correlation between Vitamin D level and VDR gene ApaI polymorphism nor with serum lipoprotein levels. But we found that women-carriers A-allele VDR gene ApaI polymorphism had higher serum total cholesterol (5.52±0.08 and 5.18±0.15; p<0.05) and LDL levels (3.56±0.07 and 3.29±0.13; p<0.05), than a-allele carriers. Conclusions: Results of this study showed that A allele carriage (AA and Aa-genotypes) VDR gene ApaI polymorphism in reprodactive age women was associated with atherogenic dyslipidemia.
LIRAGLUTIDE IN PEDIATRIC T2D: SAFETY, TOLERABILITY AND PHARMACOKINETICS/PHARMACODYNAMICS
1 , T. Battelino 2 , T.M. Jensen 3 , P.M. Hale 4 , S. Arslanian 5
Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America; 2 UMC University Children’s Hospital, Ljubljana, Slovenia; 3 Novo Nordisk A/S, Soeborg, Denmark; 4 Novo Nordisk Inc., Princeton, New Jersey, United States of America; 5 Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
Objective: Youth T2D is increasing, with few medications approved for its treatment. In a randomized, double-blind, placebo-controlled trial we evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of liraglutide in adolescents (ages 10-17 years) with T2D on diet/exercise or metformin therapy. Methods: We randomized 21 subjects 2:1 to liraglutide (n=14) or placebo (n=7). Liraglutide started at 0.3mg SC once daily, and escalated weekly over 5 weeks to 1.8mg/day based on tolerability. Results: Groups were similar at baseline. No serious adverse events (SAEs), including severe hypoglycemia were reported. Gastrointestinal AEs (most commonly diarrhea) were reported during liraglutide dose-escalation, most frequently at 0.3mg (35.7%). Minor hypoglycemia was reported in a small number of patients at 0.3 and 0.6mg liraglutide, but not at 0.9, 1.2 or 1.8mg. There was an elevation in lipase levels in 4 liraglutide patients (to 53, 56 and 74U/L at follow-up; 60U/L in one patient with elevated baseline levels), normal amylase levels and no clinical evidence for pancreatitis. Calcitonin levels were normal following treatment (males 3-18 years ≤3.51pmol/L; females 3-18 years ≤1.46pmol/L) in all liraglutide-treated subjects (mean±SD for males: 0.55±0.50; females: 0.17±0.14). After liraglutide 1.8mg, mean t½ was 12h and CL/F 1.7L/h (adults: t½ 13h, CL/F 1.2L/h, shown previously). After 5 weeks, HbA1c reduction was greater with liraglutide vs. placebo (-0.86 vs. 0.04%, p=0.0007). Conclusion: Liraglutide was well tolerated by youth with T2D, with safety, tolerability and PK profiles similar to adults. A larger-scale trial is planned to investigate safety, tolerability and efficacy in pediatric T2D.
METFORMIN (MET) PREVENTS WEIGHT GAIN IN RESIDENTIAL PSYCHIATRIC YOUTH ON SECOND GENERATION ANTIPSYCHOTICS (SGA)
, D. Tsevat, P. Steiner, M. Sorter, L.M. Dolan
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
Met treatment abrogates abnormal weight gain in many youth taking SGAs. However, no standard criteria exist regarding treatment initiation or dosing. To address these issues, two separate groups of residential psychiatric patients were started on Met: GROUP 1: those on SGAs for ≥ 2 months, with BMI was > 85th%ile and >7% body weight gain over the preceding 2 months or with BMI was > 95 %ile (n=36: age 13.8 ± 2.8 years [mean ± SD, 5.3-18y], 49% female, 45% African American); GROUP 2 (n=19) those started on Met and SGAs simultaneously. Met dose was increased over 2 months to weight stability. GROUP 1 weight increased 8.3% over 2 months prior to Met (BMIz from 1.35 ± 0.74 to 1.63 ± 0.58). Their BMIz stabilized over 4 months on Met (-0.01 ± 0.33), with continued efficacy after 6 months. Within GROUP 1, the BMIz change on Met was similar in those with or without a > 7% weight gain over 2 months prior to Met (0.04 ± 0.3 v -0.08 ± 0.35). GROUP 2 BMIz decreased more than GROUP 1 over 4 months on Met (from 2.24 ± 0.38 to 2.18 ± 0.37) and their daily Met dose was less (709.27 ± 258.87 mg v 829.15 ± 276.53 mg). In a controlled residential psychiatric setting, Met prevents weight gain on SGAs. This effect may be greater, requiring less Met, with simultaneous initiation of SGA and Met. Determining risk factors for SGA associated weight gain would allow more focused Met therapy.
GLYCOGEN SYNTHASE KINASE 3ß (GSK3ß) POSITIVELY REGULATES TLR3-MEDIATED CYTOKINES PRODUCTION
1 , J.H. Park 1 , S.Y. Lee 1,2
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea; 2 Deptartment of Bioinspired Science, Ewha Womans University, Seoul, Korea
Toll-like receptor 3 (TLR3) plays important roles in innate immune systems by producing type I interferons and proinflammatory cytokines. Although it is well known that GSK3ß is critical for the production of inflammatory cytokines in TLR-mediated signaling, how GSK3ß regulates TLR3 responses is poorly understood. To determine whether GSK3ß also regulates TLR3-mediated inflammatory cytokines production, we established the GSK3ß knockdown stable macrophage cell lines. Here we show that inhibition of GSK3ß attenuates the TLR3 agonist poly (I:C)-induced cytokines production. Suppression of GSK3ß expression drastically reduced the induction of c-fos protein by decreasing phosphorylation of extracellular signal-regulated kinase (ERK) and p38. In addition, GSK3ß interacts with TNF receptor associated factor 6 (TRAF6) and TGFß-activated kinase 1 (TAK1), which are required for TLR3-mediated mitogen-activated protein kinases (MAPKs) signaling cascade. Taken together, these findings demonstrate a regulatory function of GSK3β in TLR3-mediated proinflammatory cytokines production.
MOLECULAR SPECIES OF DIACYLGLYCEROL AND TRIGLYCERIDE, AND LIPOLYSIS IN ADIPOSE TISSUE OF OBESITY/DIABETES MODEL MICE
, M. Fukata, M. Tamura, N. Tagawa
Kobe Pharmaceutical University, Kobe, Japan
A new genetic animal model of type 2 diabetes, the Tsumura Suzuki Obese Diabetes (TSOD) mouse, has been developed in 1999. The TSOD mouse develops a moderate degree of obesity and diabetes. The aim of this study was to investigate the levels of molecular species of triglycerides (TG) and diacylglycerol, and regulation of lipolysis in adipose tissue of TSOD mice. Methods: Twelve-week old TSOD and the age-matched control (TSNO) male mice were obtained. Epididymal adipose tissue was removed and extracted lipids by Bligh & Dyer‟s method. Extracted lipids (tripalmitolein, trimyristin, triolein, tripalmitin, trilinolein, 1-palmitin-2-stearin-3-olein, 1-palmitin-2-olein-3-stearin, 1-myristin-2-olein-3-palmitin, 1-palmitin-2-linolein-3-stearin, 1-stearin-2-palmitin-3-olein, 1-palmitin-2-olein-3-linolein, 1.3-distearin, 1.3-dipalmitolein, 1.3-dipalmitin, 1.3-diolein, 1.3-dilinolein) were quantified by LC-MS (Orbitrap Discovery). The mRNA expressions of adipose tissue glycerol lipase (ATGL), hormone sensitive lipase (HSL), adipose phospholipase A2 (AdLPA2) and perilipin were also measured by real-time PCR. Results: There were no changes of the level of molecular species of TG between TSOD and TSNO except tripalmitin. Tripalmitin level in TSOD was significantly lower than that of TSNO. 1.3-Diolein level in TSOD were significantly higher than that in TSNO. 1.3-Dilinolein and 1.3-dipalmitin level in TSOD were also higher than those in TSNO, although those levels were not statistically significant. Expression of ATGL, HSL and perilipin was lower in TSOD than that in TSNO. Moreover, mRNA expression of AdPLA2 in TSOD was significantly higher than that in TSNO. Conclusions: Dysregulation of lipolysis and lipid metabolism in adipose tissue were observed in TSOD. These contribute in part to the development of obesity in TSOD mice.
GLYCAEMIC VARIABILITY AND HYPOGLYCAEMIC EPISODES WITH METFORMIN, GLARGINE, AND COMBINATION THERAPY IN T2DM USING CGM
1 , F. Schaper 2 , F. Pistrosch 2 , J. Steiner 1 , R. Staudte 1 , W. Landgraf 3 , S. Bilz 2 , C. Schoner 2 , M. Hanefeld 2 ,
GWT-TUD GmbH, Dresden, Germany; 2 Center of Clinical Studies GWT-TUD, Dresden, Germany; 3 3rd Medical Department, TU Dresden, Dresden, Germany & Sanofi Germany
Aim: Antidiabetic treatments can lower HbA1c to target but may vary in their glycaemic variability (GV) and hypoglycaemia risk (HR) with insulin being discussed to show greatest GV and HR. We used continuous glucose monitoring (CGM) to assess GV and duration of hypoglycaemic episodes (HE) in early type 2 diabetes patients (T2DM) treated with monotherapy metformin (M) or glargine (GLA) compared to combination (GLA-M) therapy in longer duration T2DM. Methods: Pooled, retrospective, descriptive analysis of 185 eligible CGM profiles from T2DM patients with drug treatment over ≥6 months recorded in RCTs in our center (M=82; GLA=78; GLA-M=25). CGM (Medtronic) was performed for 72h to measure interstitial glucose (iG). AUC-24h, AUC-2h after standardized testmeal (TM), standard deviation of mean iG (SD-iG), mean average glucose excursions (MAGE), and day-to-day variation between day 2 and 3 of CGM were calculated. Threshold for HE was <3.0 mmol/l iG. Results: Characteristic of patients for M, GLA, and GLA-M were: age 64.0/64.0/64.7yrs; BMI: 30.0/29.7/30.4kg/m²; diabetes duration: 4.7/4.9/9.9yrs; HbA1c: 6.4/6.1/6.8%. CGM results: AUC-24h: 2005/1936/2087 (ns); AUC-2hTM: 217/204/231 (ns); SD-iG: 1.40/1.66/1.87mmol/l (p<0.05, M vs. GLA, GLA-M); MAGE: 3.7/4.3/5.4mmol/l (p<0.05, GLA-M vs. GLA, M). No difference in day-to-day variability was found between groups. Overall HE duration was similar in M, GLA and GLA-M groups (10.1/18.5/22.9 min/24h, ns). Conclusion: Early insulin treatment with glargine is not associated with a substantial increase in glycaemic variability and hypoglycaemia risk compared to metformin even when approaching tight HbA1c control in T2DM patients. Longer diabetes duration may increase glucose variability despite target glycaemic control.
EXERCISE CAPACITY AND MORTALITY IN OVERWEIGHT AND OBESE INDIVIDUALS WITH TYPE 2 DIABETES MELLITUS
1,2,3 , C.J. Faselis 1,2 , J. Myers 4 , R. Kheirbek 1,2 , J.P. Kokkinos 1 , A. Pittaras 1,2 , M. Doumas 1,2
Veterans Affairs Medical Center, Washington, DC., United States of America; 2 George Washington University, Washington, DC., United States of America; 3 Georgetown University School of Medicine, Washington, DC., United States of America; 4 Veterans Affairs Medical Center, Palo Alto, California, United States of America
Introduction: Overweight and obesity often coexist with type 2 diabetes mellitus (DM2), worsening management and outcomes. Physical activity is an integral part of DM2 management. However, the interaction between fitness, body fat and mortality in diabetics has not been fully explored. Method: We assessed the association of exercise capacity and mortality risk in 3,601 individuals (mean age: 59±10) with DM2. All underwent exercise stress testing. Four fitness categories (quintiles) were established based on peak metabolic equivalents (METs) achieved: Least-Fit (<5.5 METs; n=945); Low-Fit: 5.6-7.0 METs; n=905); Moderate-Fit: 7.1-9 METs; n=868) and High-Fit (>9 METs; n=883). Individuals were also classified based on body mass index (BMI) as normal weight (BMI <25); overweight (BMI: 25-29.9) and obese (BMI ≥30). Results: There were 810 deaths (median follow-up 9.8 years). After controlling for age, risk factors and medications, we observed an inverse and graded association between exercise capacity and mortality risk for the entire cohort and within BMI categories, ranging from 33% to 70% (p<0.001). When comparing normal weight individuals with exercise capacity ≤7 METs, versus overweight/obese individuals with exercise capacity >7 METs, we noted that the risk for the overweight and obese, but fit individuals was 65% lower (p<0.001). Conclusion: An inverse and graded association between fitness and mortality risk in individuals with DM2 regardless of BMI. The risk for overweight and obese but fit individuals was approximately 65% lower when compared to those of normal weight and low-fit. This supports that fitness is a stronger predictor of mortality risk than ideal weight.
OPPORTUNITIES OF INSULIN PUMP THERAPY TO OVERCOME RESISTANCE TO EXOGENOUS-INJECTED INSULIN IN TYPE 2 DIABETES PATIENT- CLINICAL CASE
, Y.I. Philippov, O.M. Smirnova, A.Y. Mayorov
Endocrinology Research Center, Moscow, Russian Federation
Introduction: In some cases the increase of insulin doses in patients with type 2 diabetes does not reduce hyperglycemia. To overcome this condition is quite difficult. Clinical case: Women of 50 years old with type 2 diabetes (duration - 5 years) had inadequate glycemic control despite high insulin doses: Humulin NPH before: breakfast - 70 U, dinner - 60 U, supper - 60 U and Humalog – 48 U/day. Total 238 U/day (2.3 U/kg). Insulin was appointed a year ago, doses were gradually increased due to the high blood glucose levels. BMI - 34,1 kg/м2, HbA1c -7,7%. CGM showed changes from 5.5 to 15.0 mmol/l. Other endocrinology disorders were not detected. Patient had contraindications to metformin and pioglitazone. We used sensor augmented pump insulin therapy (Medtronic Paradigm Real-Time MMT-772). Basal rate (Humalog): from 24.00 to 8.00 - 3.5 U/h, from 8.00 to 24.00 – 4 U/h, bolus delivery - 10-16 U -3 times a day. After 4 days glycemic control was significantly improved and the daily dose of insulin decreased to 104 U/day (1.02 U/kg) with fasting glucose levels 6.1 - 7.0 mmol/l, postprandial 8-10 mmol/l. Conclusions: Inefficiency of large doses of insulin (resistance to exogenous-injected insulin) to a certain extent has been associated with chronic overdose of insulin. The use of insulin pump therapy allowed to overcome this condition and normalize glycemia in a type 2 diabetes patient.
SAFETY RESULTS FROM OCAPI: A EUROPEAN OBSERVATIONAL COHORT STUDY OF INSULIN GLULISINE-TREATED CHILDREN AGED 6 TO 12 YEARS WITH TYPE 1 DIABETES
1 , V. Loizeau 2 , V. Pilorget 3 , A. Cali 3 , T. Danne 4
University Pediatric Hospital, Sofia, Bulgaria; 2 Lincoln, Boulogne Billancourt, France; 3 Sanofi, Paris, France; 4 Auf der Bult, Diabetes Centre for Children, Hannover, Germany
Aims: Children with type 1 diabetes mellitus (T1DM), especially younger children, are at risk of clinically significant hypoglycaemia. The aim of OCAPI was to evaluate the safety of insulin glulisine in children with T1DM in a clinical-practice setting. Methods: A 6-month, observational, prospective cohort study of children with T1DM aged 6–12y on a stable insulin regimen for ≥3 months, for whom insulin glulisine was prescribed. Primary endpoint was incidence of severe hypoglycaemia in children aged 6–12y. Secondary endpoints included incidence of severe hypoglycaemia (in children aged 6–8y), and symptomatic hypoglycaemia, injection-site/systemic hypersensitivity reactions, and medication error in both age groups. Results: 94 patients were analysed, of which 31 were aged 6–8y. The mean time from first prescription of insulin to inclusion was 2.3 and 2.8y in the 6–8 and 9–12y groups, respectively; mean HbA1c at study end was 8.2% and 8.3%, respectively. Basal insulin dose increased in both groups, whilst short-acting insulin dose increased in the 9–12y group only. Number of daily basal insulin injections did not change. Severe hypoglycaemia occurred in 3 patients (1 in 6–8y, 2 in 9–12y group), with an overall incidence of 6.6 events/100 patients/y. The incidence of symptomatic documented hypoglycaemia was higher in the 6–8y group compared with the 9–12y group (7007.2 vs 5717.5 events/100 patients/y). Conclusions: Although previous evidence suggests that hypoglycaemia is frequent in children with T1DM, these findings suggest insulin glulisine is a safe treatment option in this patient population.
MULTIMORBIDITY IN THE PATIENTS WITH DIABETES MELLITUS AND ARTERIAL HYPERTENSION AS BASIS FOR DIFFICULTIES IN DIAGNOSTICS AND TREATMENT
1 , O.M. Iakovenko 2 , N.P. Prikhodko 1 , N.G. Tretiak 1 , M. Sulaiman 1
Higher State Educational Institution of Ukraine HSEIU “Ukrainian Medical Stomatological Academy”, Poltava, Ukraine; 2 V.P. Komissarenko Institute of Endocrinology and Metabolism AMS Ukraine, Kyiv, Ukraine
Aim: Identify multimorbidity triggers in the patients with diabetes mellitus (DM) and arterial hypertension (AH) to optimize the quality of diagnosis, treatment. Patients and Methods: The study involved 81 patients with various combinations of DM (including 5 – with 1st DM) with AH and acute or chronic coronary artery disease (CAD), pathology of the digestive system. Research methods included biochemical, hemostatic, metabolic parameters, cardiac biomarkers, interleukin-10 (IL-10), high sensitive C-reactive protein, auto-antibodies to chaperone 60 (anti-Hsp 60); daily arterial pressure (AP), electrocardiographic monitoring. We used the MiniMed Paradigm Real-Time insulin pump and continuous glucose monitoring system for 1st DM patients. Statistical parametric and nonparametric analysis was made using SPSS v. 13.0. Results: The main predictors of complicated course of CAD in the patients with DM and AH was instability of the glycemic profile, increasing the amount of monocytes and neutrophils above 75%, the index value of leukocytes to the blood cholesterol more than 1,21 conventional union, anti-Hsp 60 over 66,67 ng/ml, IL-10 less than 70 pg/ml (P by ANOVA, Kruskal-Wallis tests <0,05). Diastolic blood pressure and heart rate multiplied by the systolic blood pressure have a direct correlation average force (r=0.645, P=0.0001). AP elevation and hyperglycemia was observed in 84,4% of episodes (P<0.01 by criteria of sign). Conclusion: Multimorbidity triggers in the patients with DM and AH are the instability of the glycemic profile, disturbances of lipid metabolism, consumption syndromes of pro-inflammatory and anti-inflammatory, pro-ischemic and anti-ischemic factors. It‟s may be basis to optimize treatment, overcoming polypharmacy.
ASSOCIATION OF HEALTH BEHAVIORS, USE OF PREVENTIVE SCREENING SERVICES, AND INSIGHT AND TREATMENT OF CHRONIC DISEASES: CROSS-SECTIONAL STUDY USING KNHANES IV
, B. Cho
Seoul National University Hospital, Korea
Background: The aim of this study is to examine the difference of participation rate in blood pressure, fasting blood glucose and cancer screening and insight and medication of chronic disease across adults with different level of health behaviors among Korean general population. Methods: We used KNHANES IV. Study population consisted of 6516 individuals. Health behaviors were composed of smoking, alcohol consumption and exercise, and composite score. Health screening consisted of blood pressure, fasting glucose and cancer screening. Insight of a disease was defined as a self-report of any prior diagnosis of that disease, and medication of a disease was defined as taking prescribed medication for control of that disease when they had insight of their disease. We conducted multivariate logistic regression models to elucidate association of health behavior with health screening, insight and treatment of chronic diseases. Results: Higher health behavior score was associated with more increased likelihood to be screened in blood pressure, fasting glucose and cancer(P for the trend: 0.003, <0.001, <0.001, respectively). In each type of cancer, stomach, breast, and colon cancer were positive association with health behavior rate. (P for the trend: <0.001, <0.001, <0.001 respectively) As higher the health behavior score was, subjects were significantly more likely to report insight of hypertension, diabetes mellitus and hyperlipidemia (P for the trend: 0.012, 0.045, 0.025, respectively). No significant relationship between health behavior and medication was found. Conclusion: Higher score of health behaviors is associated with higher participation in health screening services and having insight of chronic diseases. Their relationship seems to be clustered. However, the association wasn‟t expanded to treatment of chronic disease. Additional research is needed to this point.
WAIST-TO-HIP RATIO AND BODY MASS INDEX AS PREDICTORS OF CARDIOVASCULAR DISEASE
1,2 , I. Skuja 1,3 , G. Krievina 4 , I. Stukena 1,2 , A. Jurka 4 , P. Tretjakovs 1
Riga Stradins University, Riga, Latvia; 2 Riga East Clinical Universal Hospital; 3 General Practitioner Practice; LU, 4 Institute of Experimental and Clinical Medicine, Riga, Latvia
Introduction: Obesity increases the risk of CVD in the general population. The relative importance of the body mass index (BMI) and the waist-to-hip ratio (WHR) as predictors of cardiovascular disease is still debatable. The aim of this study was to compare BMI and WHR as indices of obesity and to assess correlations between the obesity measurements and CVD risk factors. Methods: The associations with CVD risk factors were estimated in 96 clinically healthy subjects (39 were men) aged 37.4±4.0. The following BMI and WHR correlations were estimated-systolic and diastolic blood pressure (SBP and DBP), heart rate (HR), glucose, , total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-c and LDL-c), HDL-c/LDL-c, moncyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor-alpha (TNFα). SBP, DBP and biochemical parameters were measured by standard procedure. MCP-1 and TNF-α levels were measured by Luminex -xMAP technology. Statistical analyses were made by using SPSS-20. Results: We found positive correlation between BMI and WHR (r=0.62*). Both BMI and WHR correlated with SBP (r=0.80; r=0.54*), DBP (r=0.49*; r=0.46*), HDL-c (r=-0.33*; r=-0.44*), HDL-c/LDL-c (r=-0.39*; r=-0.47*) and TG (r=0.52*; r=0.54*). Only BMI correlated with TC (r=0.23**), HR (r=0.24**) and MCP-1(r=0.40**), while WHR correlated with TNFα (r=0.48**).*p<0.001,**p<0.050. Conclusions: BMI and WHI are associated with traditional CVD risks and markers of inflammation. Our result reveals it is impossible to give priority to any of those two parameters because both assert one another. To evaluate patient‟s CVD risk it is useful to estimate both BMI and WHR to assure CVD prophylaxis.
EFFECT OF THE HAPTOGLOBIN 2/2 GENOTYPE ON ENDOTHELIAL DYSFUNCTION IN TYPE 1 DIABETES MELLITUS
1 , C. Gutiérrez 2 , A. Cano 1 , P. Gil 2 , O. Giménez-Palop 1 , J. Vendrell 2 , J.M. González-Clemente 1
Diabetes, Endocrinology and Nutrition Department, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí UAB, Sabadell, Spain.; 2 Diabetes, Endocrinology and Nutrition Department, Hospital Universitari Joan XXIII, Institut Pere Virgili, CIBERDEM,Tarragona, Spain
Background and aims: Haptoglobin (Hp) is a potent antioxidant protein, which is encoded by two different alleles (1 and 2). In diabetes, Hp2/2 genotype has been associated with an elevated cardiovascular (CV) risk as compared with Hp1/1 and 2/1 genotypes. Our aim was to explore the mechanisms underlying this association in a group of subjects with type 1 diabetes (T1DM) in relation to arterial stiffness (AS) and endothelial dysfunction (ED). Material and methods: 137 T1DM patients of at least 5 years of disease duration and without previous CV disease were evaluated for: 1) age, gender, smoking, BMI, blood pressure, HbA1c and lipid profile, 2) microvascular complications, 3) AS assessed as aortic pulse wave velocity (aPWV), 4) serum markers of ED (ICAM-1, VCAM-1 and E-Selectin) and 5) Hp genotypes. Results: The frequency of the Hp1/1, Hp2/1 and Hp2/2 genotypes was 28.5%, 46.7% and 24.8%, respectively. There were no differences in traditional CV risk factors between Hp 2/2 genotype subjects (cases) and Hp 1/1-2/1 genotype subjects (controls). Diabetes duration and metabolic control were not different between the two groups. No significant differences were found for aPWV. Markers of ED were higher in the Hp 2/2 genotype group compared with Hp1/1-2/1 group (ICAM-1: p=0.007, VCAM-1: p=0.022, E-Selectin: p=0.853, ED general Score: p=0.051). Multiple regression
analyses revealed that Hp2/2 was independently associated with ED after adjusting for CV risk factors (p=0.047). Conclusion: Hp 2/2 genotype is associated with an increased ED in patients with T1DM independently of traditional CV risk factors.
THE PREVALENCE OF LATENT TUBERCULOSIS IN PATIENTS WITH DIABETES MELLITUS IN A LOCAL TERTIARY HOSPITAL: COMPARISON OF THE T-SPOT TB TEST WITH THE TUBERCULIN SKIN TEST
1,2 , R. Dalan 1,2 , C.B.E. Chee 1,3 , A. Earnest 2 , D.E.K. Chew 1 , A. Tan 1 , W.Y.C. Kon 1 , M. Jong 1,2 , S.Y.T. Wang 1,2,3
Tan Tock Seng Hospital, Singapore; 2 Duke-NUS Graduate Medical School, Singapore; 3 Tuberculosis Control Unit, Singapore
Introduction and Background: Diabetes mellitus (DM) confers tuberculosis (TB) risk 2-3 folds above non-diabetics (1). Yet, much controversies surround advocating routine TB screening and anti-TB chemoprophylaxis for latent TB infection (LTBI) in DM. We conducted a cross-sectional study to elucidate the TB prevalence and longitudinal follow-up to ascertain LTBI to active TB conversion rate in DM. Methods: 218 DM (4.8% type 1 vs. 95.2% type 2) without TB history were recruited. T-Spot test, tuberculin skin test (TST) and chest radiography (CXR) were concurrently performed. TST >= 10 mm at 72 hours was positive. LTBI was defined by negative CXR with positive T-Spot. Conversion to active TB was confirmed by cross-checking the cohort against the national TB registry. Multiple logistic regression was used to identify independent predictors among covariates of demographics, DM history, co-morbidities and HbA1c. Results: LTBI prevalence was 31.2%. Only 14.1% had both positive T-Spot and TST. If only TST was employed, 17.8% with positive T-Spot and negative TST would have been missed while 14.6% with positive TST and negative T-Spot would have been misdiagnosed as LTBI. One had active TB at enrolment. None converted to active TB over 6 years. Age > 60 years (p=0.025), comorbidity (p=0.047) and ischemic heart disease (IHD) (p = 0.010) were associated with LTBI in the univariate analysis, though only IHD remained significant in the multivariate model. Discussion: Approximately one-third of DM patients harbour LTBI. This warrants further research to determine the risk:benefit ratio of anti-TB chemoprophylaxis and establish consensus in formulation of TB screening policy in this population.
Reference: 1. Dooley K E, Chaisson R E. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 2009;9:737-46.
HYPERTENSION IN OVERWEIGHT TYPE 2 DIABETICS: ASSOCIATION OF INCREASED LEPTIN LEVELS AND INSULIN RESISTANCE
1,2 , N.M. Lalic 1,2 , A. Jotic 1,2 , N. Rajkovic 1,2 , N. Milicic 2 , M. Zamaklar 1,2 , K. Lalic 1,2 , J.P. Seferovic Mitrovic 2 , M. Macesic 2 , J. Stanarcic 2
Medical Faculty, University of Belgrade, Belgrade, Serbia; 2 Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia
Aims: Increased leptin levels associated with insulin resistance (IR), represents a well established risk factor for development of hypertension. We analyzed the levels of (1) adipocytokines and (2) IR in: overweight (30≤BMI≥25kg/m2) T2D patients with hypertension (group A, n=48,), without hypertension (group B, n=43) and nondiabetics without hypertension (group C, n=40). Methods: Hypertension was defined as systolic BP ≥140 and diastolic BP ≥ 90mmHg. IR was measure with two complementary indexes: (1) oral glucose insulin sensitivity (OGIS) and (2) homeostasis model assessment of insulin resistance (HOMA-IR). Results: We have found the highest leptin and resistin levels in group A ( Leptin: A: 12.68+/-3.41; B: 8.53+/-3.42; C: 6.85+/-2.68 pg/ml A vs B p<0.05; A vs C p<0.01 and B vs C p<0.05; Resistin: A: 10.4 ± 4.1; B: 6.97± 2.72; C: 4.88 ± 2.41 pg/ml; A vs B p<0.05; A vs C p<0.01 and B vs C p<0.05). There were no significant differences in adiponectin levels between diabetics (A: 4.70+/-1.23; B: 4.39+/-1.31; C: 7.67+/-1.33 ng/ml, A vs B p=NS). Simultaneously, we have found significantly higher HOMA-IR ( A: 9.43+/-2.69; B: 7.52+/-2.08; C: 5.73+/-1.83; A vs B; A vs C and B vs C p<0.05) and lowest OGIS in group A (A: 287.67±35.42; B: 359.22±32.0; C: 494.29±23.81; A vs B p<0.05; A vs C p<0.01 and B vs C p<0.05). An increased leptin levels negatively correlate only with OGIS (r=-0.347; p<0.05). Conclusion: Our results imply that increased leptin levels influence the presence of hypertension in overweight diabetic patients through peripheral insulin resistance.
THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF EMPAGLIFLOZIN, A POTENT SODIUM GLUCOSE COTRANSPORTER-2 INHIBITOR
1 , P. Rose 2 , M. Mattheus 3 , R. Cinca 4 , S. Pinnetti 2 , U.C. Broedl 3 , H.J. Woerle 3
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States of America; 2 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 3 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 4 Pierrel Research HP-RO SRL, Timisoara, Romania
Objective: Empagliflozin is a potent and selective sodium glucose cotransporter-2 inhibitor in development for the treatment of type 2 diabetes mellitus. This open-label, parallel-group study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics, safety, and tolerability of empagliflozin. Methods: Thirty-six subjects (8 each with mild, moderate or severe hepatic impairment according to Child-Pugh classification, and 12 matched controls with normal hepatic function) received a single 50 mg dose of empagliflozin. Results: Mean (range) age was 53.9 (33–71) years and 17 subjects were male. Empagliflozin was rapidly absorbed and, after reaching peak levels, plasma drug concentrations declined in a biphasic fashion. Compared with subjects with normal hepatic function, geometric mean ratios (90% CI) of AUC0–∞ and Cmax were 123.15% (98.89–153.36) and 103.81% (82.29–130.95), respectively, in patients with mild hepatic impairment, 146.97% (118.02–183.02) and 123.31% (97.74–155.55), respectively, in patients with moderate hepatic impairment, and 174.70% (140.29–217.55) and 148.41% (117.65–187.23), respectively, in patients with severe hepatic impairment. Adverse events (AEs) were reported in 0, 3 and 2 subjects with mild, moderate and severe hepatic impairment, respectively, and 6 subjects with normal hepatic function. All AEs were mild or moderate in intensity. Conclusions: Empagliflozin was well tolerated in subjects with hepatic impairment. The increase in empagliflozin exposure was less than 2-fold in patients with impaired liver function, therefore no dose adjustment of empagliflozin is required in these patients. These data were presented at ADA 2012. Funded by Boehringer Ingelheim.
THE ROLE OF THE ENZYME 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 IN HUMAN OBESITY
, H. Zamrazilová, M. Bičíková
Institute of Endocrinology, Prague, Czech Republic
Adipose tissue as an endocrine organ produces factors that significantly affect energy balance of the body. These factors include the steroid hormones, especially estrogens and glucocorticoids. Human 11β- hydroxysteroid dehydrogenase type 1 (11 β-HSD1) acts as a steroid oxidoreductase, which is responsible for the reversible oxidation not only of cortisol to cortisone but also of two endogenous dehydroepiandrosterone metabolites, 7α-hydroxy-dehydroepiandrosterone (7α-OH-DHEA) and its 7β-hydroxyisomer (7β-OH-DHEA) to 7-oxo-dehydroepiandrosterone (7-oxo-DHEA). We investigate how the activity of the enzyme is changing before and after 1 month of treatment in obese adolescent patients. Inclusion criteria: age from 12.0 to 17.9 years, BMI greater than the 90th percentile relative to age and sex. Exclusion criteria: endocrinopathies including diabetes of the first type, using of drugs that affect body weight. We focus on the serum levels of especially less common steroids (cortisol, cortisone, 7-oxo-DHEA, 7α-OH-DHEA and 7β-OH-DHEA) which are indicators of enzymatic
activity of 11 β-HSD1. Metabolites of dehydroepiandrosterone are determined by highly specific radioimmunoassay. Cortisol and cortisone are analyzed by high performance liquid chromatography with UV/VIS detection. Normostenic controls are also investigated. Based on measured data we would like to clarify the role of the enzyme 11 β-HSD1 in human obesity with the subsequent use of inhibitors of this enzyme for therapeutic purposes.
PREDICTING FACTORS FOR DAILY INSULIN REQUIREMENT AT THE ONSET OF TYPE 1 DIABETES
, H. Ben Abdessalem, E. Haouat, L. Ben Salem, C. Ben Slama
National Institute of Nutrition, Tunis, Tunisia
The aim of this study is to determine the daily requirement of insulin (IU/kg/day) in patients at the diagnosis of type 1 diabetes and to analyse features affecting these requirements. Methods: Retrospective study of 50 inpatients collected at the onset of type 1 diabetes. Results: Patients were males in 68 % of cases (n=34). Mean age at the diagnosis was 22.2 years (ext: 6-38) and mean body mass index (BMI) 21.8kg/m2 (ext: 14,5-32,4). Diagnostic circumstances were ketosis in 74% of cases (n=37), hyperglycaemia without ketosis in 20% (n=10) and ketoacidosis in 6% of cases (n=3). Mean HBA1C was 13.8 % (ext: 8-18.1%). A basal-bolus insulin treatment was prescribed in all patients. Insulin used was NPH + actrapid in 90 % of cases and long + rapid acting analogues in 10% of cases. Mean daily insulin dose was 0.7 IU/kg/d (0.3–2 IU/kg/d). No significant difference for daily insulin doses was found with gender, age, and initial HBA1c level. Insulin doses were higher for the lower BMI without any significant difference. Doses were significantly higher in case of initial ketoacidosis than in case of ketosis and isolated hyperglycaemia (1.42 IU/Kg/d vs 0,66 IU/kg/d ; p=0.018). Insulin doses were higher when using rapid and long acting analogues than NPH and actrapid (0.8 IU/kg/d Vs 0.7IU/Kg/d ; p=0.6). Conclusion: Age, gender, HBA1c level at diagnosis don‟t affect initial insulin requirement in type 1 diabetes. Insulin doses are higher in case of diabetes revealed by ketoacidosis.
DIABETIC NEPHROPATHY IN TYPE 2 DIABETES: MPO T-764C AND INOS SER608LEU GENOTYPE RELATED TO OXIDATIVE STRESS
1 , D. Petrovič 2
Slovenj Gradec General Hospital, Slovenj Gradec, Slovenia; 2 University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
Background: Diabetic nephropathy is a chronic complication of diabetes, related to high cardiovascular morbidity and mortality. There is evidence for a genetic susceptibility to development, progression and final stage of diabetic kidney failure, but we are not yet able to predict which patient will develop the disease. Due to the known correlation to oxidative stress we tested 10 oxidative stress related gene polymorphisms in type 2 diabetic patients and analyzed their correlation to diabetic nephropathy development. Patients and methods: 197 Slovenian type 2 diabetic patients, age 34-83, classified into two groups according to the presence of diabetic nephropathy, were tested for SOD2 Val16Ala, p22 phox C242T, CAT C-262T, MPO T-764C, GSTP1 Ile105Val, GSTT1 and GSTM1 deletion polymorphisms, eNOS Glu298Asp, eNOS 4a/b and iNOS Ser608Leu polymorphisms using PCR, RFLP and qPCR. Oxidative stress was assessed through serum 8-OHdG level. Results and conclusions: Despite the commonly recognized link between oxidative stress and diabetes and its complications we found no association between the selected polymorphisms and diabetic nephropathy. However, we confirmed a correlation between MPO MPO T-764C and iNOS Ser608Leu genotype and oxidative stress levels (p<0.05). Our results reflect the multifactorial nature of diabetic nephropathy in addition to genetic heterogeneity within and between populations.
EFFECTS OF ANTI-CD3 MONOCLONAL ANTIBODY IN EXTRACELLULAR MATRIX OF SALIVARY GLANDS OF DIABETIC MICE
, E.E. Mayoral, G.M. Domingues, A.T. Ferri, F.A. Rojas, L.A. Peroni, E.A. Lourenço, E.J. Caldeira
Faculty of Medicine of Jundiaí, Jundiaí, Brazil
Diabetes mellitus results in many complications, also compromising the salivary glands. The current treatment for this condition should be a substituting method to exogenous insulin. In this aspect, the immunotherapy has been tested, but, it can be inefficient as an agent for the control of damage caused by diabetes. Thus, the aim of this study was to evaluate the anti-CD3 monoclonal antibody as alternative immunotherapy in the recovery of salivary glands of diabetic NOD mice. Animals were divided into three groups: Group I (5 Balb/C mice untreated), Group II (5 diabetic NOD mice untreated) and Group III (5 diabetic NOD mice anti-CD3 treated). After treatment, the samples of salivary glands were collected for histological examination under both transmitted and polarized light microscopy. Parts of samples were also used to fluorescence microscopy. Alterations in tissue architecture with increase in the extracellular matrix, presence of inflammatory process and alteration in the expression of insulin receptors (INS-R) were observed in untreated diabetic animals. Recovery of salivary acinar cells occurred in the treated mice. The parotid glands demonstrated a smaller amount of collagen fibers and were not observed severe inflammatory processes, as well as in both glands were observed the recovery of INS-R expression. The results indicate that immunotherapy contributed to the reestablishment of tissue damaged by the hyperglycaemic condition, demonstrating that the immunomodulation plays an important role in the recovery of these tissues (Support FAPESP: 10/05455-8 and 10/51619-2).
REMISSION OF DIABETES AND HYPERTENSION ACCOMPANYING RAPID WEIGHT REDUCTION FOLLOWING BARIATRIC SURGERY
1,2 , L.M. Hiebert 3
Mandal Diabetes Research Foundation, St. Augustine, Florida, United States of America; 2 University of Florida, Gainesville, Florida, United States of America; 3 University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Background: In obese patients diabetes control is difficult because of insulin resistance and control of hypertension requires multiple drugs at high doses. Remission of diabetes following gastric bypass surgery is reported. Methods: This study reports an obese individual with progressive weight increase, uncontrolled diabetes and variable hypertension control despite intensive therapy. The patient‟s baseline weight was 207 lbs. which increased to 356 lbs. in 2 years, fasting blood glucose (FBG) and 2h-postprandial blood glucose (2-hPPG) increased from 131 and 181 mg/dL to 147 and 263 mg/dL respectively, despite 60 units of glargine insulin twice daily and regular insulin 5 units with each meal. Blood pressures (BP) ranged from low 130/80 to high 180/100 mmHg. Laparoscopic Roux-en-y gastric bypass surgery was performed in November 2011. Results: The patient lost 22 lbs. prior to surgery and an additional 22 lbs. immediately after. At last visit, 7 months after surgery weight was 270 lbs. with a reduction of 64 lbs. since surgery, total weight loss of 86 lbs. Sitting and standing BP were reduced to 130/70 and 90/60 mmHg respectively, resulting in reduced BP medication. FBG and 2-hPPG were reduced to 112 and 87 mg/dL respectively without insulin therapy. Mean HbA1c was 8.3% (range 7.8% - 9.3%) before surgery and 6.0% after surgery. Conclusion: Obesity and diabetes go hand in hand. Weight reduction following gastric bypass restores normoglycemia and simplifies BP control. Gastric bypass surgery is not conventional therapy but should be considered when weight reduction, diabetes and BP control cannot be achieved.
ASSOCIATION OF ≥3% WEIGHT LOSS AND SELF-REPORTED ADHERENCE WITH 6-MONTH GLYCEMIC CONTROL IN T2DM: THE DELTA STUDY
1 , B.K. Bellows 1 , G.D. Wygant 2 , J. Mukherjee 3 , S.K. Unni 1 , X. Ye 1 , J.N. Liberman 4 , U. Iloeje 3 , D. Brixner 1
University of Utah, Salt Lake City, United States of America; 2 Bristol-Myers Squibb, Princeton, United States of America; 3 Bristol-Myers Squibb, Wallingford, United States of America; 4 Geisinger Center for Health Research, Danville, United States of America
Background: The association between weight loss, adherence and glycemic control in patients with inadequately controlled T2DM remains largely uncharacterized. Methods: Patients ≥18 years with T2DM from a US integrated health system who started a new anti-diabetic therapy (AD) between 11/1/10 – 4/30/11 (index date) with baseline HbA1c ≥7.0% were included. Target HbA1c and weight change were defined at 6-months as HbA1c <7.0% and ≥3% loss in body weight. Patient-reported medication compliance was assessed per the Medication Adherence Reporting Scale. Structural equation modeling was used to describe simultaneous associations between adherence, weight loss, and glycemic control. Results: Criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naïve; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index AD. At 6 months mean weight change was -1.3 (5.1) kg (p=0.39) and 28.1% had weight loss of ≥3%. Mean HbA1c reduction was -1.2% (1.8) (p<0.001) and 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p=0.02) and ADs that lead to weight loss (metformin, GLP-1) (OR 2.96; p<.001) were associated with weight loss. Weight loss (OR 3.60; p<.001) and adherence (OR 1.59; p<.001) were associated with HbA1c goal attainment. Conclusion: Though weight loss ≥3% and adherence were associated with glycemic control in T2DM, weight loss appears to be a stronger predictor of HbA1c goal attainment than medication adherence in this study population. Therefore, it is important to consider weight-effect properties, in addition to adherence counseling, when prescribing ADs.
GAPP2™ SURVEY: HYPOS MORE COMMON IN US TYPE 2 DIABETES PATIENTS, BUT IMPORTANCE UNDER-RECOGNISED
1 , M. Brod 2 , T.M. Hobbs 3 , M. Peyrot 4
University of Miami Miller School of Medicine, Miami, Florida, United States of America; 2 The Brod Group, Mill Valley, California, United States of America; 3 Novo Nordisk, Princeton, New Jersey, United States of America; 4 Loyola University Maryland, Baltimore, Maryland, United States of America
Objective: To investigate differences in self-treated hypoglycemia (hypos) in US patients with type 2 diabetes (T2DM) using insulin analog (IA) regimens we examined results from US patient and prescribers in an online survey. Research design: US data on hypos from 1850 T2DM IA treated patients and 311 prescribers are compared with data from 1192 T2DM IA treated patients and 911 prescribers from other countries (G2 = Canada, Japan, UK, Germany, Denmark). Results: Significantly more US (than G2) patients recalled hypos overall (83% vs 77%) and within the last 30 days (38% vs 32%). But significantly less US patients worried about hypos, and prescribers, particularly US prescribers, significantly underestimated patient worry. In response to their last hypo, US and G2 patients reported missing a basal insulin (BI) dose (4% vs 6%) or reducing a BI dose (8% vs 7%). US and G2 patients recalled missing a BI dose 1.9 vs 1.7 times and reducing a BI dose 5.2 vs 2.3 times. Significantly fewer US prescribers (than G2) considered hypo risk when choosing which insulin to initiate (79% vs 84%), and fewer initiated on lower than recommended dose (49% vs 58%) to avoid hypos. Furthermore, fewer US prescribers regularly discussed hypos with patients 51% vs 56% BI only and 60% vs 67% basal bolus IA patients. Conclusions: Despite higher rates, less T2DM IA users in the US worry about hypos though some still make potentially inappropriate dosing changes. These findings should alert prescribers to continuing patient education needs to overcome hypoglycemia apathy.
GLUCOSE AND GLP-1 LEVELS AFTER TEST MEAL BEFORE AND AFTER GASTRIC BYPASS SURGERY IN MORBID OBESE SUBJECTS
, D. Bajec, S. Polovina, D. Radenkovic, M. Sumarac-Dumanovic, P. Gregoric, G. Cvijovic, S. Ignjatovic, M. Dajak, D. Micic, D. Jeremic
Clinical Center of Serbia, Center for Obesity, Faculty of Medicine, Serbia
The mechanism of glycemic control after bariatric surgery is still not clear, bur various hypothesis exist about the role of GLP-1 in improvement of glucose homeostasis after gastric bypass. The aim of our study was to determine GLP-1 response after test meal (Fresubin drink a 200 ml; 200 kcal, 15 % protein, 30% fat and 55 % carbohydrate) before (day 0) and 5, 90 and 180 days after gastric bypass surgery. Glycaemia (mmol/l; glucose oxidase) and GLP-1 (Active 7-36) (pM/l; ELISA, ALPCO diagnostics) were determined in 8 obese patients (age: 31.1±14,0; BMI: 42,7±7.2 kg/m2) in four separate days in 0, 15, 30, 60, 90 and 120 min. There were no significant difference between area under the glucose curve (X ± SD) ( 652.65±57.12 vs 574.80±72.96 vs 572.62±68.36 vs 563±60.25 mmol/l x min-1; p >0.05) in respective day intervals, while there was significant increase in area under the GLP-1 curve (pmol/l x min-1) in days 5 (861.94±251.22), 90 (664.12±124.36) and 180 (751.74±575.71) in comparison with day 0 (163,00±73.61 ) (p < 0.05). There were no significant differences between basal GLP-1 levels 0, 5 and 90 days (0.56±0.25; 0.95±0.17; 0.35±0.14; p > 0.05) but there was significant increase in basal GLP-1 level in day 180 (2.75±2.92). There was significant increase in peak GLP-1 levels in day 5 (21.28±3.23), day 90 ( 26.52±4.36) and day 180 (12.78±6.47) in comparison with day 0 (1.97±0.30) (p<0.05). In conclusion, GLP-1 response after test meal is significantly increased early after gastric bypass surgery (after 5 days) and lately, after 90 and 180 days. The observed improvement in GLP-1 response after test meal among patients after gastric bypass surgery may be responsible for the metabolic effects of bariatric surgery, especially on glucose homeostasis.
INSULIN SENSITIVITY AND ANTIOXIDANT ENZYMES IN DIABETICS AND NONDIABETICS: TRANSIENT ISCHEMIC ATTACK VS STROKE
1 , N. Lalic 1 , A. Jotic 1 , V. Kostic 2 , N. Covickovic-Sternic 2 , K. Lalic 1 , M. Mijailovic 2 , L. Lukic 1 , N. Rajkovic 1 , J. Seferovic-Mitrovic 1 , M. Macesic 1 , J. Stanarcic 1
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia; 2 Clinic for Neurology, Clinical Center of Serbia, Belgrade, Serbia
Aim: The study was aimed to evaluate (a) insulin sensitivity (IS) (b) three different types of antioxidant enzyme activities, glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) in type 2 diabetics (T2D) and nondiabetics with transient ischemic attack (TIA) or ischemic stroke. Methods: We included 20 T2D with TIA (group A), 28 T2D with ischemic stroke (group B), 19 nondiabetics with TIA (group C) and 28 nondiabetics with ischemic stroke (group D). TIA and ischemic stroke was confirmed by neuroimaging criteria. IS levels were detected by minimal model analysis (Si index). GSH-Px, GR and SOD were detected by spectrophotometry. Results: Si levels were significantly lower in group B vs A (1.03+/-0.36 vs 1.84+/-0.72 min-1/mU/lx104; p<0.05) and in group D vs C (2.58+/-0.45 vs 3.77+/-0.55 min-1/mU/lx104; p<0.05). GSH-Px and GR were significantly lower in group B vs A (GSHPx: 22.4±3.2 vs 35.8±1.6; p<0.05; GR: 43.2±1.5 vs 60.3±3.5 U/gHb; p<0.05) and in group D vs C (GSHPx: 25.45±1.37 vs 37.80±1.38; p<0.05; GR: 49.5±4.89 vs 62.36±3.46 U/gHb; p<0.05), without differences in SOD. Si significantly correlated with GSH-Px and GR, both in T2D (GSH-Px: r=0.434, GR: r=0.390 p<0.05) and in nondiabetics (GSH-Px: r=0.423, GR: r=0.387, p<0.05). Conclusions: The onset of
ischemic stroke in comparison with TIA was strongly associated with decreased IS and reduced glutathione dependent type of antioxidant enzyme activity, both in T2D and in nondiabetics, suggesting that atherogenic influence of decreased IS in different cerebrovascular event severity might be exerted through a significantly reduced glutathione dependent antioxidant enzyme activity.
PREDICTION OF EXTRACRANIAL VASCULAR EVENTS IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACK
1 , M.B. Vilanova 1 , J. Montserrat-Capdevila 1 , F. Purroy 2 , M. Falguera 1 , M. Roca 1 , A. Balcells 1 , D. Rios 1 , A. Quesada 1 , M. Caldero 1 , V. Sanchez 1 , M. Pena 1
Pla Urgell Primary Care Area, Mollerussa, Spain; 2 Arnau de Vilanova Hospital, Lleida, Spain
Background: Determinants of risk of extracranial vascular events (EVE) after transient ischemic attack (TIA) are not well defined. The aim of our study was to determine the risk and risk factors for EVE (coronary heart disease [CHD] and peripheral arterial disease [PAD]) after TIA. Methods: We prospectively recruited patients within 24 hours of transient ischemic cerebrovascular events between October 2006 and June 2011. A total of 560 TIA patients were followed for six months or more. EVE and stroke recurrence (SR) were recorded. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded and established prognostic scores (CHADS2, CHADS2-VASC2, ABCD2, ABCD2I, ABCD3I, California risk score, Essen Stroke risk score and Stroke Prognosis Instrument were calculated). Results: 31 (5.9%) EVE (22 CHD and 9 PAD) and 63 (11.9%) recurrent strokes occurred during a median follow-up period of 31.3 months (18.3-47.6). Discrimination for the prognostic scores only ranged from 0.60 to 0.70. The incidence of EVE did not varied among the different etiological subtypes. In Cox proportional hazards multivariate analyses we identify alcoholism (Hazard Ratio [HR] 3.66, 95% Confidence Interval [CI] 1.10-12.13, p=0.034), hypercholesterolemia (HR 3.77, 95% CI 1.84-7.72, p<0.001), motor weakness (HR 1.73, 95% CI 1.20-2.50) and the presence of carotid plaques (HR 1.29, 95% CI 1.07-1.56, p=0.007) as independent predictors of EVE. Conclusion: According to our results, discrimination was poor for all previous risk prediction models. Variables like alcoholism, hypercholesterolemia, motor weakness and carotid plaques should be considered in new prediction models.
ASSOCIATION BETWEEN THE NUMBER OF METABOLIC FACTORS AND LEFT VENTRICULAR MASS INDEX AS ASSESSED BY 64-MULTIDETECTOR COMPUTED TOMOGRAPHY
1 , H. Urata 1 , K. Okamura 1 , S. Miura 2 , K. Saku 2
Fukuoka University Chikushi Hospita, Fukuoka, Japan; 2 Fukuoka University Hospital, Fukuoka, Japan
Increased left ventricular mass (LVM) and metabolic syndrome (MetS) are well-recognized predictors of cardiovascular morbidity and mortality in epidemiological studies. We analyzed the association between LVM as determined by multi-detector row computed tomography (MDCT), and the MetS using an accurate method for determining criteria. Subjects included 513 consecutive patients (male/female= 54%/ 46%, age= 64 ± 11 years) who underwent coronary angiography using MDCT. We quantified coronary artery calcification score, visceral fat area (VFA), subcutaneous fat area and waist circumference, and measured blood pressure, ABI and PWV. We also analyzed plasma levels of adiponectin, lipid profile, HbA1c, blood glucose and uric acid. Of the total of 513 subjects, 209 (41%) were diagnosed as MetS. LVM after adjusting for body surface area (LVM index) in subjects with hypertension was significantly higher than those without hypertension. When all subjects were divided into five groups (0-4) according to the number of metabolic factors, LVM index were significantly decreased as the number increased (trend p<0.0001). While, there was no significant association in ejection fraction as determined by MDCT in the number of metabolic factors (trend p=0.2966). In conclusion, this study showed that MetS contributed to increased LVM index without reduced LV systolic function.
PREDICTORS OF HOSPITALIZATION IN PATIENTS WITH EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
1 , P. Godoy 2 , J.R. Marsal 3 , I. Cruz 3 , M.G. Mo-Gasol 4 , M.B. Vilanova 1 , M. Caldero 1 , R. Llovet 1 , M. Álvarez 1 , X. Ferrer 1 , V. Sánchez 1 , M. Pena 1
Institut Catala de la Salut, ABS Pla d'Urgell, Lleida, Spain, 2 Medical School of University of Lleida, Spain, 3 Research Support Unit of Institut Catala de la Salut, Spain, 4 Hospital Universitari Arnau de Vilanova, Lleida, Spain
Introduction: The main objective was to determine the predictors that were associated to the hospital admission due to worsening chronic obstructive pulmonary disease (COPD). Methods: We conducted a cohort retrospective study that included 1,323 patients diagnosed with COPD in the Health Centre of the Pla d'Urgell (Lleida, Spain). They were classified into two cohorts; cohort 1: patients vaccinated against seasonal influenza during the campaign 201112, and cohort 2: non-vaccinated. Patients in both cohorts requiring hospital admission for exacerbation of the disease between the 12/01/2011 and the 03/15/2012 were quantified. Information about the variables of interest was recorded for each patient. In order to establish the variables which were associated to hospital admission, a univariate and multivariate analysis was made. Results: The score model was made up of the age, influenza vaccine, diastolic blood pressure and dyslipidemia. The variables that were associated with a hospitalization for more than 7 days were turned out to be heart disease and the ratio FEV1/FVC. Conclusion: The design of a score model about the risk prediction of the hospital admission will allow to identify all those patients with a high level risk which might could take advantage of the preventive and therapeutic strategies that they are send to prevent the hospital admission.
PREVALENCE OF PERIPHERAL ARTERY DISEASE AND METABOLIC SYNDROME IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACK
1 , M.B. Vilanova 1 , M. Caldero 1 , R. Llovet 1 , V. Sanchez 1 , M. Pena 1 , M.G. Mo-Gasol 3 , M. Abellana 1 , L. Olivart 1 , E. Miguel 1 , E. Sancho 1 , F. Purroy 2
Institut Catala de la Salut, ABS Pla d'Urgell, Lleida, Spain; 2 Neurology Department, Hospital Arnau de Vilanova, Spain; 3 Emergency Service, Hospital Arnau de Vilanova, Spain
Introduction: the main objective was to determine the prevalence of peripheral artery disease (PAD) determined through brachial ankle index (BAI) among patients with transient ischemic attack (TIA) . METHODS: We conducted a cohort prospective study that included 434 patients diagnosed with TIA in 30 spanish hospitals and 231 patients with an association of risk factors without TIA. The prevalence of metabolic syndrome was determine by a prospective way applying (American Treatment Panel III [ATP III] of 2005 and International Diabetes Federation [IDF] of 2006) criteria. The factors associated in both group were established. In order to establish the variables which were associated to TIA, a univariate and multivariate analysis was made. RESULTS: the prevalence of PAD was bigger in TIA (22,8% versus 5,6%) but not differences in prevalence of metabolic syndrome (49,5% versus 48,9%) according to ATP III and IDF criteria. The predictors associated with PAD in TIA group were: age >65 (OR 1,03 [1,01-1,05]), atheromatous etiology (OR 2,43 [1,21-4,86]), ischemic cardiopaty (OR 2,61 [1,21-5,49] and alcoholism (OR 4,97 [2,12-11,58]). For metabolic syndrome (IDF) were: dyslipidemia (OR 2,61 [1,47-4,65] and hypertension (OR 9,60 [5,29-17,43]), and for ATP-III: hypertension (OR 58,48 [20,22-169,15], diabetes (OR 3,25 [1,21-8,74], dyslipidemia (OR 2,56 [1,23-5,34]). CONCLUSION: the prevalence of peripheral arterial disease is extremely bigger in patients with TIA than controls. There are some
cardiovascular risk factors associated with the group of patients with stroke.
LONG-TERM EFFICACY AND SAFETY OF DAPAGLIFLOZIN VS GLIPIZIDE ADDED TO METFORMIN IN INADEQUATELY CONTROLLED T2DM
1 , S. Del Prato 2 , K. Rohwedder 3 , A. Theuerkauf 4 , A.M. Langkilde 5 , S.J. Parikh 6
Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany; 2 University of Pisa, Pisa, Italy; 3 AstraZeneca, Wedel, Germany; 4 ClinResearch GmbH, Köln, Germany; 5 AstraZeneca, Mölndal, Sweden; 6 AstraZeneca Pharmaceuticals, Wilmington, United States of America
Dapagliflozin (DAPA), a selective SGLT2 inhibitor, reduces hyperglycaemia in an insulin-independent manner by increasing urinary glucose excretion. Week 52 results of a randomised, double-blind trial of DAPA vs glipizide (GLIP) added to metformin (MET) in patients with T2DM inadequately controlled with MET (NCT00660907) have been previously reported. Here we present long-term results at 2 years with DAPA (n=315) vs GLIP (n=309) added to MET. Mean change from baseline in HbA1c was -0.32% (95%CI: -0.42, -0.21) with DAPA vs -0.14% (-0.25, 0.03) with GLIP. DAPA produced sustained reductions in weight: -3.70kg (-4.16, -3.24) vs +1.36kg (0.88, 1.84) for GLIP, with low risk of hypoglycaemia (4.2% DAPA vs 45.8% GLIP). Adverse events were similar between groups. Events suggestive of urinary tract infection (UTI) were reported in 13.5% DAPA and 9.1% GLIP patients, with one discontinuation in each group. Events suggestive of genital infections (GenInf) were reported in 14.8% (8.0% men, 23.3% women) DAPA and 2.9% (0.4% men, 5.9% women) GLIP patients, with three discontinuations in the DAPA group. Most events occurred in Year 1, were mild-to-moderate in intensity and responded to standard care. No discontinuations due to UTI or GenInf occurred in Year 2. There was no clinically relevant change in renal function over 2 years. Compared with GLIP, DAPA added to MET showed sustained glycaemic efficacy and weight loss, with low risk of hypoglycaemia over 2 years. Events suggestive of UTI or GenInf mostly occurred in Year 1 and rarely led to discontinuation.
THE ROLE OF OBESITY AND AGING IN CARDIOVASCULAR REMODELING IN MONOSODIUM GLUTAMATE TREATED RATS
1 , A.K. Burlá 1 , W. Oigman 1 , Z.B. Fortes 2
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil; 2 Universidade de São Paulo, São Paulo, Brasil
The monosodium-glutamate (MSG)-induced obese rat is a model associated with insulin resistance and dyslipidemia. The aim of this study was to evaluate the interaction between obesity and aging in cardiovascular remodeling. Male Wistar rats received subcutaneous injections of MSG (4.0g/kg) or saline from the second to the sixth day after birth. The sacrifices were done at week 16 and 30, resulting in two control groups (CON-16, CON-30) and two obese groups (MSG-16, MSG-30). Systolic blood pressure (SBP) was measured weekly by tail-cuff plethysmography. Myocardium tissue was stained with Sirius red. Lumen diameter, media thickness and media cross-sectional area (CSA) of intramyocardial arteries were measured. Cardiac collagen density was estimated using the Image Pro system. The Lee index was significantly higher in MSG groups (30.4±0.3 and 31.2±0.2 vs 29.5±0.2 and 29.7±1.0 g/cm, p<0.001). SBP was significantly increased in MSG-30 group (135±2 mmHg, p<0.001) comparing to MSG-16 (108±2 mmHg), CON-16 (113±2 mmHg) and CON-30 (115±1 mmHg). Media thickness of intramyocardial arteries was significantly greater in MSG-30 rats (16.3±0.2μm, p<0.01) compared to CON-16(12.5±0.5μm) and CON-30 (13.±0.4μm) groups. Media-to-lumen ratio was significantly higher in MSG-30 (51.2±1.3%) than in CON-30 (39.3±1.2%, p<0.05), CON-16 (30.2±2.0%, p<0.01), MSG-16(39.9±3.7%, p<0.05). Media CSA was also increased in MSG groups suggesting hypertrophic vascular remodeling in these animals. Myocardial collagen density was significantly greater in obese (4.0±0.5 and 5.1±0.5%) than in control rats (2.1±1.3% and 2.6±0.6%, p<0.01). We concluded that in this experimental model, the presence of obesity promoted the increase of SBP and enhanced the adverse cardiovascular remodeling observed in aging.
EFFECTS OF LIFESTYLE INTERVENTION IN PERSONS AT RISK FOR TYPE 2 DIABETES MELLITUS - RESULTS FROM A RANDOMISED, CONTROLLED TRIAL
1 , P.B. Bakke 2 , G.H. Rohde 3 , F.G. Gallefoss 4
Department of Internal Medicine, Sorlandet Hospital Kristiansand, Serviceboks 416, 4604 Kristiansand; 2 Institute of Internal Medicine, University of Bergen, Norway; 3 Department of Rheumatology, Sorlandet Hospital, Kristiansand and Faculty of Health and Sport sciences, University of Agder, Norway; 4 Chief Consultant in Pulmonology, Department of Pulmonary Medicine, Sorlandet Hospital Kristiansand, Norway
Background: Lifestyle change is probably the most important single action to prevent type 2 diabetes mellitus. The purpose of this study was to assess the effects on lifestyle change and health related quality of life (HRQOL) of a low-intensity individual lifestyle intervention. Methods: The “Finnish Diabetes Risk score” was used to identify individuals at risk. With an 18 month follow-up and a randomised, controlled design the effects of individual lifestyle counselling (IG) every six months was compared with the same individual lifestyle counselling combined with a group-based interdisciplinary program (IIG) provided over 16 weeks. Primary outcomes were changes in lifestyle (weight reduction ≥5%, improvement in VO2 max, diet improvements and changes in HRQOL). Results: 213 participants (50% women), mean age 46 years and mean body mass index 37, were included of whom 182 returned at follow-up. There were no significant differences in changes in lifestyle behaviours or HRQOL between the two intervention groups, thus effects are summarised. At least 5% weight loss was achieved by 32% and 34% improved their aerobic capacity at least one metabolic equivalent. Unhealthy diet was common at baseline(60%), but uncommon at follow-up(13%). The best predictor of improved HRQOL was a clinical significant lifestyle change (both a weight reduction of 5% and improvement in VO2 max at least 10%). Conclusion: It is possible to achieve important lifestyle changes and moderate improvement in HRQOL in persons at risk for type 2 diabetes with modest clinical efforts. No additional effects were achieved by group intervention.
CANAGLIFLOZIN COMPARED TO GLIMEPIRIDE IN SUBJECTS WITH TYPE 2 DIABETES ON BACKGROUND METFORMIN
1 , W.T. Cefalu 2 , L.A. Leiter 3 , J. Xie 4 , D. Balis 4 , W. Canovatchel 4 , G. Meininger 4
Central Hospital Central Finland, Jyväskylä, Finland and University of Eastern Finland, Kuopio, Finland; 2 Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America and LSUHSC School of Medicine, New Orleans, Louisiana, United States of America; 3 Saint Michael’s Hospital and University of Toronto, Toronto, Canada; 4 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
Canagliflozin (CANA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is being developed for the treatment of type 2 diabetes mellitus (T2DM). This randomized, double-blind, active-controlled, Phase 3 study evaluated CANA 100 or 300 mg compared with glimepiride (GLIM) (titrated to 6 or 8 mg/day; mean 5.6 mg) in subjects with T2DM inadequately controlled with metformin (MET) (N=1,450; age 56.2 years; A1C, 7.8%; body mass index, 31.0 kg/m2). At 52 weeks, A1C was reduced with CANA 100 and 300 mg and GLIM (–0.82%, –0.93%, and –0.81%, respectively). Both CANA doses demonstrated non-inferiority and CANA 300 mg demonstrated superiority to GLIM in reducing A1C. CANA was also associated with body weight reductions and lower documented hypoglycemia rates compared with GLIM (P<0.001 for all), and showed improvements in FPG, systolic blood pressure, triglycerides, and HDL cholesterol, with a small, dose-related increase in LDL cholesterol. Incidences of
adverse events (AEs) were similar with CANA 100 and 300 mg and GLIM (64.4%, 68.5%, and 68.5%, respectively). Serious AE and AE-related discontinuation rates were low. Incidences of AEs consistent with genital mycotic infections were higher with CANA 100 and 300 mg than GLIM (women, 11.3% and 13.9% vs 2.3%; men, 6.7% and 8.3% vs 1.1%). CANA showed slightly higher rates of urinary tract infections (6.4% and 6.4% vs 4.6%) and osmotic diuresis-related AEs (eg, pollakiuria; <3% per specific AE). In summary, CANA showed consistent A1C lowering and reduced body weight compared with GLIM, and was well tolerated in subjects with T2DM inadequately controlled with MET.
TREATMENT STRATEGY FOR HYPERTENSIVE PATIENTS WITH LOW, MEDIAN AND HIGH CARDIOVASCULAR RISK NOT CONTROLLED WITH VALSARTAN/HYDROCHLOROTHIAZIDE
A. Abuab, F.T. Neves
Hospital Universitario Pedro Ernesto, Rio de Janeiro, Brazil
This study analyzed the efficacy of triple combination (TC) therapy strategy for achieving goal blood pressure (BP) in hypertensive patients (P) not controlled with valsartan/hydrochlorothiazide (V/HCTZ) with low (LR), medium (MR) and high (HR) cardiovascular risk (CVR) in accord with Brazilian and international guidelines. P. After 12 weeks of treatment with a V/HCTZ plus amlodipine (A) treatment algorithm the BP goal was SBP <140 mmHg and DBP < 90 mmHg for LR, SBP <130 and DBP < 85 mmHg for MR and SBP <130 and DBP < 80 mmHg for HR P. The regimen started with low dose TC 160V/12.5HCTZ/5A mg. P who did not meet target BP were randomized in a ratio of 1:1 to receive one of two TC regimens; either 160mgV/12.5mgHCTZ /10mg A or 160mgV/25 mg HCTZ /5 mgA. Patients who still did not meet target BP entered the high-dose TC 160 mg V/25 mg HCTZ /10 mg A, once daily for the final 4 weeks. The BP control was achieved in 81,2% in LR, 76,5% in MR and 48,6% in HR hypertensive P. There was a progressive increase in BP reduction from low dose to the highest triple combination dose considering: S and DBP basal BP minus final achieved BP (1º phase 12,5 / 6,5 mmHg; 2º phase 14,9/8,4 mmHg and 3º phase 21,7/12,0 mmHg). Peripheral edema was the most frequent event. Overall, most P with LR (81,6%) and MR (76,5%) achieved BP goal with TC.
EARLY ONSET OF GLYCAEMIC IMPROVEMENTS AFTER INSULIN INITIATION WITH GLARGINE IN T2DM PATIENTS UNCONTROLLED WITH OADS
1 , M.P. Dain 2 , W. Landgraf 3
Cardiff University, Wales, United Kingdom; 2 Sanofi, Paris, France; 3 Sanofi-Aventis, Frankfurt, Germany
Aim: to evaluate early glycaemic improvements with insulin glargine after first 12 weeks of treatment when added to oral anti-diabetic drugs (OADs) in uncontrolled type 2 diabetes patients (T2DM). Method: randomized controlled clinical trials (≥24 weeks) with glargine added to lifestyle intervention and/or stable OAD therapy in T2DM, using a pre-defined insulin dose mmol/l and with FPG and HbA1c values at interim 12 weeks were analysed retrospectively. Results: Eight studies (TREAT-to-TARGET; LANMET; INSIGHT; TRIPLE THERAPY; INITIATE; APOLLO; L2T3; EASIE) with a total of 1793 patients were included for early efficacy assessment after glargine initiation. Prior (and continued) therapies included 0-4 OADs. Mean baseline FPG ranged from 9.1-13.0 mmol/l across studies and were reduced to between 3.2-6.6 mmol/l at week 12. Similarly, mean baseline HbA1c (range: 8.5-9.5%) decreased by 1.4-1.7% across studies at 12 weeks and was maintained or further improved to between 1.5-2.4% at ≥24 weeks, the endpoint of the studies. In addition, glycaemic control with glargine therapy was associated with a low risk of hypoglycaemia across studies. Conclusion: Basal insulin initiation with glargine demonstrates an sustained response on glycaemic control observed within first weeks of initiation of insulin treatment in insulin-naïve, T2DM patients inadequately controlled on OADs.
CARDIOVASCULAR RISK MANAGEMENT AND LIPID CONTROL IN DIABETIC AND NON DIABETIC PATIENTS IN A PRIMARY CARE SETTING
M. Pape, A. Smagadi, I. Haritonidis
Health Centre of Soxos, Ahepa University Hospital of Thessaloniki, Thessaloniki, Greece
The aim of this study was to assess the prevalence of cardiovascular diseases risk factors (arterial hypertension, diabetes, obesity, smoking dyslipemia) in diabetic and non-diabetic patients attending a primary care setting in northern Greece. A total of 287 patients (198 women / 89 men) were avalaible for analysis. An over-night fasting blood sample was taken for total cholesterol (CHOL), triglycerides (TG), low density lipoprotein (LDL) and Hemoglobin A1c (HbA1C) determination. Hypertension, diabetes, obesity and smoking were identified in 53,6%, 23,6%, 27,7% and 18,1% of the subjects, respectively. Dyslipemia was determined as follow: Chol (men: 59,5% / women: 68,7%), TG (men: 34,8% / women: 36,8%), LDL (men: 55,05% / women: 60,06%). Glycemic control was optimal (HbA1C 6,1-7%) in 54,3%, fair (HbA1C 7-7,9%) in 34,7% and poor (HbA1C >8%) in 10,8% of the diabetic patients, receiving anti-diabetic medication. Glycemic control was poor in 77% of the insulin-dependent patients. The incidence of cardiovascular diseases risk factors is increased in our population. Therefore it is necessary for the primary care to take immediate actions, such as lifestyle modifications and drug treatment, in order to reduce the cardiovascular risk.
OMEGA 6 INTAKE MODULATES GLICEMIC CONTROL: RANDOMIZED, CONTROLLED AND DOUBLE BIND STUDY
C. Pappiani, N.R.T. Damasceno
Department of Nutrition, School of Public Health University of Sao Paulo, Sao Paulo, Brazil
Background: The effect of fat on lipid metabolism is amply investigated and now quality, more than quantity, is focus of many studies. Despite of this, the role of fat on glucose metabolism and development of diabetes is sparkly describe in literature. Objective: Evaluated the effect of omega-6 in glycemic level in patients with or without glucose imbalance. Methods: A randomized, controlled and double bind study enrolled 142 subjects, both gender and 30-74 years old. Subjects were submitted to intervention (placebo versus omega-6; 3g/d) during 8 wk. At basal time and after intervention, sample blood was collected after 12h of fasting. Biochemical analysis (lipid profile, glucose), clinical and socio-demographic data were performed by standard methods. Statistical analysis was performed by SPSS 15.0 at significance level of p <0.05. Results: Omega-6 group (n=72) shows subjects with a mean age of 51.9 years old, 82 % women, and 77.8 % under use of hypoglycemic drug. The placebo group (n=70) was characterized by patients with a mean age of 54.4 years, 58.6% women and 18.6% under use of hypoglycemic drug. Intra-group analysis showed significant reduction of fasting blood glucose (p = 0.025), with median values of 97 (91 to 114.25 mg/dl) (T=0) versus 95 (89.3 to 105 mg/dl) (T=8) in omega-6 group, but placebo group did not show significant changes (p=0.277). However, inter group comparison did not show difference (p=0.548). Lipid profile remains unchanged after intervention. Conclusion: Supplementation with omega-6 was effective after 8 wk of intervention, reducing the values of fasting. This result shows the positive role of omega-6 in the disturbances of glucose
METABOLIC SYNDROME IN THE HYPERTENSIVE: CAN LARGE EVENING MEAL BE THE CULPRIT?
1 , H.J. Yoon 2
1 Department of Family Medicine, Seoul National University Hospita, Seoul, Koreal; 2 Department of Medical Engineering, Seoul National University Hospital, College of Medicine, Seoul, Korea
Background: A diverse investigations are performed in an effort to understand and slow down the epidemic of metabolic syndrome (MetS). Dietary habits are acknowledged to be in close relationship with metabolic derangements. Objective: In this study, we aimed specifically to investigate the impact of the circadian phase of food consumption on whether large evening meals are associated with metabolic syndrome parameters. Design: We performed a cross-sectional analysis on data from 6,308 participants from the Fourth National Health and Nutrition Examination Survey. The National Cholesterol Education Program criteria were used in the definition of MetS. Subjects were evaluated for MetS and its components across different amount of evening intake. Subjects were evaluated again after stratification according to gender, age group, total calorie, body mass index, medical treatment of hypertension or diabetes, and sleep duration. Results: No significant relationship was found between the amount of evening intake and MetS or its components. However, in the antihypertensive medication group, the risk for having MetS increased across the tertiles, but not in the hypoglycemic medication group. Subjects in tertile 2 showed a 71% increase (p=0.019), while subjects in tertile 3 showed a 203% increase in the likelihood of having MetS (p=0.011), compared to subjects in tertile 1 where evening intake was the smallest (219.25±129.84 kcal/day). Conclusion: Our research shows that the risk of MetS or its components do not differ among evening calorie intake, but in the hypertensive population, large meals in the evening were related to higher risk of MetS.
ANTI-OSTEOPOROTIC ACTIVITY OF PIG PLACENTA HYDROLYSATES IN OVARIECTOMIZED RATS
1 , B.S. Ko 2 , J.A. Ryuk 2
Department of Food & Nutrition Hoseo University, Asan, Korea; 2 Korea Institute of Oriental Medicine, Daejeon, Korea
Placenta hydrolysates from various animal sources have been used to attenuate post-menopausal symptoms including osteoporosis. However, their effects have been scientifically studied. The purpose of the study was to determine the anti-osteoporotic effect of two types of pig placenta hydrolysates (PPH) in obese-induced rats. Forty female Sprague–Dawley rats were randomly assigned into sham-operated group (Sham) and four ovariectomized (OVX) subgroups: original PPH (1 g/kg bw/day; OPPH), modified PPH (1 g/kg bw/day; MPPH), estrogen replacement (0.1 mg/kg bw conjugated estrogen; EST), and dextrose (placebo; OVX-control). The assigned compounds with a high fat and calcium deficient diet were orally and daily given for 12 weeks. OPPH contained very low levels of estrogen and progesterone but it contained more essential amino acids (34%) while MPPH had estrogen (712 pg/100 mg) and progesterone (7.4 ng/100 mg) but less essential amino acids (23%). OPPH decreased body weight and epididymal fat pads and maintained uterus weight in OVX rats. BMD and BMC of the femur and lumbar spine were higher in OPPH than the control but their increase in OPPH was smaller than EST. Serum Ca and P levels exhibited the increase in OPPH compared to the control while urinary Ca and P levels were decreased in OPPH. Serum alkaline phosphatase and osteocalcin levels, bone turnover markers, lowered in OPPH than the control. MPPH showed the similar pattern to OPPH in all the parameters but it had a less effects. In conclusion, OPPH had a definite antiosteoporotic effect without hyperplastic effect on uterus, possible with various amino acid compositions, but probably not with gender hormones. OPPH might be a potential alternative medicine for treatment of postmenopausal osteoporosis.
EFFECT OF CENTRAL AMPK ACTIVATION ON INSULIN SECRETION AND INSULIN RESISTANCE IN TYPE 2 DIABETES RATS
1 , J.A. Ryuk 2 , B.S. Ko 2
Food & Nutrition, Hoseo University, Asan, Korea; 2 Korea Institute of Oriental Medicine, Daejeon, Korea
Background and aims: As AMP-activated protein kinase is activated in energy deficient states, it suppresses the enzymes to synthesize of protein, and carbohydrates to consume ATP while it activates the enzymes to produce ATP. In the present study, we investigated the effect of hypothalamic AMPK activation on energy and glucose metabolism and hepatic insulin signaling in 90% pancreatectomzed rats. Results: In the hypothalamus, AICAR activated the phosphorylation of AMPK and compound C suppressed the activation. However, isoproterenol did not activate AMPK phosphorylation. AICAR slightly increased food intake in the first week of treatment but it was not different after the second week while energy expenditure and total activity decreased in AICAR+compound C treatment. These changes resulted in increased epididymal fat pads. Serum glucose levels increased in AICAR-treated rats and decreased isoproterenol-treated rats during oral glucose tolerance test. Insulin secretion in first phase decreased in AICAR treatment in hyperglycemic clamp while it was increased by isoproterenol. Glucose infusion rates during euglycemic hyperinsulinemic clamp, representing insulin sensitivity, is increased in isoproterenol-treated rats and they were reversed with compound C treatment. However, AICAR and isoproterenol did not alter insulin signaling in the liver. AICAR decreased the phosphorylation of AMPK while AICAR+compound C reversed the phosphorylation. Isoproterenol increased the phosphorylation of STAT3 and compound C reversed the increase. Conclusion: Isoproterenol did not activate hypothalamic AMPK and it had different action mechanism. Central AMPK activation increased epididymal fat pads by short-term increase of food intake and reduction of energy expenditure in type 2 diabetic rats.
BODY WEIGHT AND SEX AFFECT APPETITE HORMONES IN RESPONSE TO MACRONUTRIENT INGESTION BY ADOLESCENTS
1 , G.H. Anderson 1 , S. Vien 1 , N. Bellissimo 2 , B. McCrindle 3 , J. Hamilton 3
University of Toronto, Toronto, Canada; 2 Ryerson University, Toronto, Canada; 3 Hospital for Sick Children, University of Toronto, Toronto, Canada
The interaction between body weight (BW) and sex on appetite hormone responses to a mixed macronutrient beverage has not been fully elucidated during adolescence. We examined blood glucose (BG), insulin, total PYY, active ghrelin and subjective appetite responses to a mixed glucose and whey protein beverage in NW (15-85th percentile) and OB (>95th percentile) adolescents. After a 12 h fast, 9 NW (5F, 4M) and 9 OB (5F, 4M) adolescents consumed a 250 ml glucose (30 g) and whey (30 g) beverage. Hormones, BG and appetite were measured at baseline and every 15-30 min for 120 min. As expected, area under the curves (AUCs) for BG and insulin were higher and ghrelin lower in OB vs. NW adolescents (p < 0.050). The drop in ghrelin (0-30 min) was blunted in OB vs. NW adolescents (-21 vs. -183 pg/ml, p = 0.036). Similar to insulin, PYY and appetite0-60min AUCs (p < 0.048) were higher in OB vs. NW adolescents. Insulin AUC was positively correlated with PYY AUC in OB adolescents only (r = 0.901, p = 0.001). Mean insulin over time was higher in males vs. females (p = 0.006), primarily due to the increase in OB males (p = 0.024). Likewise, mean PYY over time was higher in males vs. females (p = 0.032). Thus, BW and sex affect macronutrient-stimulated appetite hormone secretion with diminished ghrelin and greater insulin and PYY responses in OB adolescents, more in males than in females, suggesting impaired satiety occurs. (Grant funding, CIHR).
ASSESSMENT OF CYSTATIN C FOR DETERMINING RENAL FUNCTION IN TYPE 2 DIABETIC PATIENTS
1 , I. Risovic 2 , V. Vlatkovic 3 , S. Avram 4 , R. Beric 5 , B. Vukovic
Clinic for Endocrinology, Diabetes and Metabolism, Clinical University Center of Banja Luka, Republic of Srpska, Bosnia and Herzegovina; 2 International Dialysis Center, Laktaši, Republic of Srpska, Bosnia and Herzegovina; 3 Clinic of Internal Diseases, Clinical University Center of Banja Luka, Republic of Srpska, Bosnia and Herzegovina; 4 Institute of Laboratorial Diagnostic, Clinical University Center of Banja Luka, Republic of Srpska, Bosnia and Herzegovina; 5 International Dialysis Center, Banja Luka, Republic of Srpska, Bosnia and Herzegovina
Early identification of renal damage is crucial in diabetic patients. Recent data suggest that cystatin C could be a sensitive marker of renal function, especially in population like older patients, pediatric population, and patients with diabetes mellitus. The aim of the study was to determine the renal function in type 2 diabetic patients using cystatin C and creatinine clearance, and compared this two test. We studied 60 subjects, who were divided into two groups: 30 patients with type 2 diabetes mellitus(DM) and 30 healthy subjects. Serum creatinine, serum cystatin C and 24-hour creatinine clearance were determined in all subjects. Diagnostic efficiency was calculated from receiver operating characteristic (ROC) curves.In this study cystatin C was more sensitive marker (0,941 vs 0,769) and more specific marker (0,93 vs 0,809) in all subjects, especially in type 2 diabetic patients when compared with creatinine clearance. Area under the ROC(AUC)of cystatin C was significantly greater (p< 0.000) than that creatinin clearance (0.963 vs 0.815). Cystatin C was more specific and sensitive marker of renal function than creatinine clearance in type 2 diabetic patients.
THE IMPACT OF COMPREHENSIVE PATIENT MANAGEMENT WITH STRUCTURED SELF MONITORING BLOOD GLUCOSAE ON GLYCAEMIC CONTROL IN DIABETES MELLITUS TYPE 2
1 , Z.V. Asimi 2
Clinic for Endocrinology, Diabetes and Metabolism, Clinical University Center of Banja Luka, Republic of Srpska, Bosnia and Herzegovina; 2 University Clinical Center Sarajevo, Clinic for Endocrinology, Diabetes and Metabolic Disease, Bosnia and Herzegovina
We report findings from a 6-month, observational study that assessed the impact of structured Self Monitoring Blood Glucose (SMBG) with diabetes self-management training on glycaemic control in type 2 diabetic (T2DM) patients. The aim of study was to investigate the impact of comprehensive patient management with structured SMBG on glycaemic control in T2DM. 150 diabetic patients (69 females and 82 males), recruited and managed by healthcare professionals from the primary care, under the supervision of two diabetes clinics in Bosnia and Herzegovina. Patient`s mean(SD) age was 59(8.40) years and mean(SD) duration of diabetes 8.98(6.84) years. All patients participated education sessions with AccuCheck Assist, structured educational program and they were training to use AccuCheck 360o View tool. They performed the 7-point blood glucose profiles trough three consecutive days on the beginning, after 3 and 6 months. Well-Being Survey and Physician Questionnaire were administered at study end. The parameters which were observed at baseline and last visit are: HbA1c, mean blood glucose values, Total cholesterol, LDL, HDL, Triglycerides, Blood pressure, Weight, BMI, Waist circumference. There was reduction in mean(SD) HbA1c from baseline a relatively low level 7.97%(1.6) to 7.28% (1.15)Δ-0.69%. At 6th visit, reductions in mean blood glucose values were recorded for all 7 daily measurement points.Improvement was also found in a number of other observed parameters. Structured SMBG, combined with patient education, significantly improves glycaemic control in T2DM patients. Thus structured SMBG and patients education appear to be both coast effective and useful in clinical practice
LIRAGLUTIDE IN PAEDIATRIC SUBJECTS WITH T2D: A POPULATION PK ANALYSIS AND COMPARISON WITH ADULTS
1 , L.V. Jacobsen 1 , T.M. Jensen 1 , D.J. Klein 2
Novo Nordisk AS, Søborg, Denmark; 2 Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Background: Only metformin and insulin are approved for treating paediatric subjects with T2D (10-17-year-olds). With the increasing prevalence of T2D in paediatric populations, a medical need exists for more treatment options. This analysis investigated the pharmacokinetics of liraglutide in paediatric subjects compared with two previous liraglutide PK trials in adults. Methods: A one-compartment model with first-order absorption and elimination was used to estimate clearance (CL/F) and distribution volume (V/F) for liraglutide using pooled data from three PK trials. AUC<SS0-24h> (SS, steady state) derived from CL/F and dose was used to investigate dose-proportionality in paediatric subjects. Covariate analysis investigated effects of dose, weight, gender and age (paediatric/adult) on liraglutide exposure. Trial : n=13 paediatric, plasma samples (0-13h, 0-24h for final dose) collected following daily liraglutide doses (weekly increases) of 0.3, 0.6, 1.2, and 1.8mg steady-state. : n=12 adults; : n=32 adults, plasma samples from trials  and  (0-60h, 0-24h, respectively) collected at 1.8mg steady-state. Results: PK data indicated dose-proportionality for model-derived AUCSS0-24h . Weight and gender were significant covariates for exposure in both age groups – AUC<SS0-24h> decreased with increasing weight. Mean AUC<SS0-24h> was 63% higher at lowest weight (53kg), 56% lower at highest weight (216kg), compared with median (90kg). Males had 31% lower exposure than females. CL/F estimates were comparable for children and adults. Conclusion: The regimen used for liraglutide treatment of T2D in adults achieved comparable exposure in the paediatric population studied. A large-scale trial is planned to investigate safety, tolerability and efficacy of liraglutide in paediatric T2D.
ASSOCIATION BETWEEN JOB STRAIN AND CARDIOVASCULAR RISK IN WORKERS OF A PUBLIC UNIVERSITY
1 , G. Kac 2 , S.M.F. Silqueira 3
Universidade Federal de Minas Gerais, Nursing School, Maternal Child Nursing And Public Health Department, Belo Horizonte, Brazil; 2 Universidade Federal do Rio de Janeiro, Josué de Castro Nutrition Institute, Brazil; 3 Universidade Federal de Minas Gerais, Nursing School, Basic Nursing Department, Belo Horizonte, Brazil
Objective: To estimate the association between job strain and high cardiovascular risk. Methods: This is a cross-sectional study, developed with 211 employees of public university health campus of Minas Gerais State, Brazil. Job strain was defined according to Karasek demand-control model, while high cardiovascular risk, was based on Framingham score. The relationship between job strain and high cardiovascular risk was estimated using Prevalence Ratio (PR) and its 95% confidence interval (95% CI), adjusted for potential confounding factors, and calculated through Poisson regression. Results: Job strain and high cardiovascular risk were present in 28.4% and 28.0% of the subjects, respectively. In the bivariate analysis, night work, passive and job strain demand-control scale categories, work time > 120 months, schooling ≥ 9 years, familiar income ≥ 6 minimum salaries, abdominal obesity level 2 and triglycerides ≥ 150 mg/dl were associated with high cardiovascular risk (p < 0.05). After multivariate analysis, job strain remained independently associated with high cardiovascular risk (PR = 2.73; 95% CI = 1.43 – 9.77). Conclusions: The prevalence of elevated cardiovascular risk was high among workers exposed to psycho-emotional stress in workplace. This finding should be considered in new policies regarding workers quality of life and primordial health promotion that may culminate with changes in labor relationships.
METABOLIC SYNDROME IN EMPLOYEES AT A PUBLIC UNIVERSITY: ASSOCIATED FACTORS AND CONCORDANCE BETWEEN DIAGNOSIS CRITERIA
A.M. Pimenta, A.L.M. Leão
Universidade Federal de Minas Gerais, Nursing School, Maternal Child Nursing And Public Health Department, Belo Horizonte, Brazil
Objective: To analysis the factors associated with MetS and the concordance between diagnosis criteria between health campus employees at a public university. Methods: Epidemiological, cross-sectional and analytical study involved 211 health campus employees in the city of Belo Horizonte, the State of Minas Gerais, Brazil. Subjects answered a questionnaire containing demographic, socioeconomic, anthropometric and life-style variables. MetS was defined according to criteria proposed by NCEP-ATP III, IDF and NHLBI/AHA. Statistical analyses were descriptive (absolutes and relatives frequencies), bivariate (Person‟s chi-square and Fisher exact tests) and multivariate (Poisson regression), with a significance level of 5% (p < 0.05). Concordance of MetS definitions was evaluated with Kappa test. Results: MetS prevalences were 27% (95% CI: 21.1-33.5) NCEP, 33.2% (95% CI: 26.9-40) IDF and 28.4% (95% CI: 22.5-35%) NHLBI/AHA. Overweight and obesity were independently associated with MetS for all diagnosis criteria. Furthermore, income ≥ 6 minimum wages (PR = 0.52; 95% CI = 0.29-0.95) NCEP, very dependent on social support (PR = 1.55; 95% CI = 1.08-2.21) IDF and age (PR = 1.02; 95% CI = 1.00-1.04) NHLBI/AHA also were independently associated with MetS. The percentages of concordance between the diagnosis criteria were high (> 85%). According to Kappa test, NCEP and NHLBI/AHA were the two diagnosis criteria most concordance (0.965; p < 0.001). Conclusion: MetS prevalence was high and should be considered in discussions on worker health promotion. Results demonstrated the necessity of consensual MetS diagnosis criteria.
EXERCISE CAPACITY AND LONG TERM MORTALITY IN HYPERTENSIVE MEN 70 YEARS AND OLDER
A. Pittaras, C.J. Faselis, M. Doumas, J.P. Kokkinos, P.F. Kokkinos
Veterans Affairs & George Washington University Medical Centers, Washington, District of Columbia, United States of America
Introduction: Chronological aging in healthy subjects is associated with declines in muscle mass, strength, endurance, and aerobic fitness. Older individuals respond favorably to exercise, suggesting that physical inactivity plays an important role in age-related dysfunctions. Conversely, physical activity and improved exercise capacity is associated with lower mortality risk in hypertensive individuals with and without additional risk factors. However, the impact of increased exercise capacity in older hypertensive individuals has not been investigated extensively. Methods: A total of 1,306 hypertensive men, age ≥70 years of age from the VAMC, Washington DC underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved, adjusted for age: Low-Fit: <5 METs (n=654); Moderate-Fit 5.0-7.5 METs (n=402); and High-Fit: >7.5 METs (n=250). All-cause mortality is reported with a mean follow-up period of 8.3+/-5.4. Cox proportional hazard models were applied after adjusting for age, BMI, history of CV disease, CV medications and traditional CV risk factors. P-values <0.05 using two sided tests were considered statistically significant. Results: There were a total of 559 deaths (42.8%) or 52 deaths per 1000 person-years of follow-up. For every 1-MET increase in exercise capacity, the mortality risk was lowered by 16% (HR=0.84; CI: 0.79-0.89; p<0.001. Mortality risk decreased across fitness categories. The association was inverse and graded. More specifically, compared to the Low-Fitness category, mortality risk was 33% (HR=0.67; CI: 0.55-0.81; p<0.001) and 63% (HR=0.37; CI: 0.27-0.50; p<0.001) lower for those in the Moderate and High fitness categories, respectively. Conclusions: Aerobic capacity is strongly associated with lower mortality risk in hypertensive individuals ≥70 years old.
METABOLIC IMPROVEMENTS SIX MONTHS AFTER BARIATRIC SURGERY
D. Bajec, M. Sumarac Dumanovic, D. Radenkovic, D. Stamenkovic Pejkovic, G. Cvijovic, D. Micic, J. Glikogorijevic, D. Jeremic, D. Micic
Clinical Center of Serbia, Center for Obesity, Belgrade, Serbia
Introduction: Obesity is associated with changes in metabolic parameters (e.g. serum lipids, bood glucose, C-reactive protein toleration) and could cose accelerating atherosclerosis and cardiovascular diseases. Methods: we have analyzed BMI, lipid profile, HbA1c and C reactive protein in 60 obese subjects, 20 males and 40 females, 38.3 (±17.6) years of age, with BMI 44.07 ±7.1 kg/m2, before and six monts after bariatric surgery. Mean blood glucose was 5.11mmol/l, HbA1c 5.77%, total cholesterol 5.18mmol/, HDL-c 1.10mmol/l, LDL-c 3.15mmol/l, tg 2.22mmol/l, CRP 13.3mg/l. All of them were operated by laparoscopic restrictive-malapsorptive bariatric technique (Roux en Y gastric by pass) and also, all of them were on 1000kcal, balanced diet three weeks before bariatric procedure and on restrictive medical nutritive therapy after operation. Results: Six monts after bariatric surgery BMI was 33.19kg/m2, decreased 24.9% ( p<0.05), HbA1c 5.24%, decreased 9.18% (p<0.05), s-cholesterol 4.1mmol/l, decreased 20.8% ( p<0.01), LDL cholesterol 2.2mmol/l, decreased 43.1% (p<0.01), triglycerids 1.42mmol/l, were lower 48% (p<0.01). No significant changes we found in HDL cholesterol level, which was 1.07mmol/l (p>0.05) after 180 days. C reactive protein was 2.07mmoll, and that was significant decrease of 83% (p<0.001). Conclusion: weight reduction duoe to bariatric restrictive-malabsorptive procedures, and following medical nutritive therapy, improves lipid parameters, glycated hemoglobin, attenuates systemic inflammation and lowering risk for atherosclerosis and also, for cardiovascular diseases.
SAFETY OF DAPAGLIFLOZIN IN CLINICAL TRIALS FOR T2DM
1 , S.J. Parikh 2 , K.M. Johnsson 3 , A.M. Apanovitch 2 , J.E. Sugg 1 J.F. List 2
Bristol-Myers Squibb, Princeton, United States of America; 2 AstraZeneca Pharmaceuticals, Wilmington, United States of America; 3 AstraZeneca, Mölndal, Sweden
Dapagliflozin (DAPA), a selective SGLT2 inhibitor, lowers blood glucose by increasing renal glucose excretion. Safety data were pooled from short-term, double-blind periods of 12 placebo (PBO)-controlled trials (>4500 patients) investigating 2.5, 5, and 10 mg doses of DAPA. Adverse events (AEs) were slightly more common with DAPA (60.6–61.9%) vs PBO (56.9%). Serious AEs and discontinuations due to AEs were similar across groups. Hypoglycaemia was more common with DAPA (10.7–16.3%) vs PBO (8.0%), driven by imbalances with DAPA added to sulfonylurea or insulin. Genital infections were more common and urinary tract infections (UTI) slightly more common with DAPA vs PBO. Mean changes in systolic/diastolic blood pressure were -4.0/-2.0mmHg DAPA vs -0.9/-0.5mmHg PBO, without increased orthostatic hypotension (3.9% DAPA vs 3.7% PBO). Volume depletion AEs (hypotension/dehydration/hypovolaemia) were seen in 0.6–1.2% DAPA vs 0.4% PBO patients. AEs of renal impairment/failure were similar across groups (0.9–1.4% DAPA vs 0.9% PBO). Small increases in haematocrit, serum magnesium and phosphorus were seen with DAPA. All DAPA doses from 19 Phase 2b/3 trials were reviewed for rare events. Incident rates for malignancies were similar for DAPA (1.4%) vs control (1.3%); breast and bladder cancer events were more common with DAPA. Elevated liver laboratory tests were similar to control. Cardiovascular (CV) death, myocardial infarction, stroke or hospitalization for unstable angina were similar for DAPA vs control (HR 0.82; 95% CI: 0.583, 1.152). Trends in CV events and specific malignancies will be further evaluated in a randomized CV outcomes trial and complementary observational studies.
EDUCATION OF ADULTS WITH TYPE 1 DIABETES IN LATIN AMERICA AND THE MIDDLE EAST: RESULTS FROM THE IDMPS
1 , P. Aschner 2 , J. Chan 3 , J.M. Chantelot 4 , E. Genestin 4 , M.P. Dain 4 , H. Ilkova 5 , F.J. Lavelle-González 6 , J.J. Gagliardino 7
India Diabetes Research Foundation, Dr A. Ramachandran's Diabetes Hospitals, Chennai, India; 2 Endocrinology Unit, Javeriana University, Bogotá, Colombia; 3 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; 4 Sanofi, Paris, France; 5 Department of Internal Medicine, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; 6 Facultad de Medicina y Hospital Universitario, Monterrey, Mexico; 7 Center of Experimental and Applied Endocrinology, La Plata National University, La Plata, Argentina
Aims: In order to achieve and maintain glycaemic targets, additional data on diabetes management is required. One of the aims of the International Diabetes Management Practices Survey is to understand the impact education has on diabetes management. Methods: An ongoing 5-year, multi-national, observational study in patients with T1DM and T2DM in Latin America (LA) and the Middle East (ME). Data were collected over a period of 4 years in LA (2693 patients) and 3 years in ME (1316 patients) and pooled. Patient profiles were determined by logistic regression analysis. Results: Diabetes education was received by 65.3% of patients in LA and 58.9% in ME. Education delivered individually, collectively or both was given to 60.3%, 29.2% and 10.6% of patients in LA, and 69.7%, 20.2% and 10.1% of patients in ME, respectively. <15% of patients in LA and ME belonged to a patient diabetes association. Use of a basal-prandial insulin regimen was higher in patients receiving diabetes education in LA and ME. Glycaemic control was also higher in patients trained by a diabetes educator in both regions. In LA, diabetes education was significantly (P < 0.05) associated with patients recruited by specialists, glucometer use, self-management (self-monitoring blood glucose and self-adjustment of insulin) and HbA1c <7%. In ME, diabetes education was significantly associated with glucometer use, self-management, basal-prandial insulin regimen (vs basal regimen) and HbA1c <7%. Conclusions: Diabetes education appears to be associated with better glycaemic control in both regions. Access to diabetes education should be given to all patients with T1DM.
THE EFFECT OF VISCERAL FAT AREA AND ADIPOCYTOKINES ON ACUTE MYOCARDIAL INFARCTION:
A CASE-CONTROL STUDY IN ADULT KOREAN POPULATION
J. Rho, K. Lee, Y. Suh, K. Yum
The Catholic University of Korea Saint Vincent's Hospital, Suwon City, South Korea
Background: This study aimed to analyze visceral fat area (VFA) and the pattern of secretion of adiponectin, leptin, TNF-α, IL-6, and IL-10. It also studies the effect of VFA and adipocytokines on the risk of Acute myocardial infarction (AMI) in adult Korean population. Methods: A patient group (PG) consisting of 121 patients, who were hospitalized for AMI from 2008 to 2009, and a control group (CG) consisting of 115 healthy adults, who visited the same hospital for health examination within the same period, were included in this study. Physical measurements were performed and VFA was measured using computed tomography. Lipid, metabolic index, adipocytokine levels were also measured after 12 hours of fasting. Results: BMI, waist circumference, levels of leptin, TNF-α, and IL-6 were significantly higher in the PG, while adiponectin level was significantly higher in the CG. According to the comparison study analyzed by gender, VFA level was significantly higher in the PG, and IL-10 level was significantly higher in the CG. After adjusting for the conventional risk factors (CRF) of AMI, regression analysis showed that adiponectin and IL-10 levels reducedthe risk of AMI; whereas VFA, TNF-α, leptin, and IL-6 increased the same risk. Conclusion: It is postulated that adipocytokines and VFA will act as independent risk factors of AMI regardless of CRF of coronary artery disease.
REDUCED NOCTURNAL HYPOGLYCAEMIA WITH INSULIN DEGLUDEC VS INSULIN GLARGINE: A 2-YEAR TRIAL IN TYPE 2 DIABETES
1 , B. Zinman 2 , A. Philis-Tsimikas 3 , B. Cariou 4 , Y. Handelsman 5 , T. Vang Skjøth 6 , A. Rana 6 , C. Mathieu 7
Endocrine and Metabolic Consultants, Rockville, United States of America; 2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada; 3 Scripps Whittier Diabetes Institute, La Jolla, United States of America; 4 Department of Endocrinology, Nantes University Hospital, Nantes, France 5 Metabolic Institute of America, Tarzana, United States of America; 6 Novo Nordisk A/S, Søborg, Denmark; 7UZ Gasthuisberg, Leuven, Belgium
This 2-year, treat-to-target, non-inferiority study (1 year core followed by 1 year extension) compared the efficacy and safety of the new ultra-long-acting basal insulin degludec (IDeg) with insulin glargine (IGlar) in type 2 diabetes. Subjects were randomised 3:1 to IDeg or IGlar once daily ±OADs. Data at the end of 2 years‟ treatment are presented. Of 1030 subjects (mean age 59 years; diabetes duration 9.2 years; HbA1c 8.2%; fasting plasma glucose [FPG] 9.7 mmol/L), 725 entered the extension and 659 (IDeg: 505; IGlar: 154) completed 2 years of treatment. Mean HbA1c reductions were similar: 1.0% (IDeg) vs 1.1% (IGlar); estimated treatment difference [ETD] IDeg-IGlar: 0.12% [95%CI −0.01; 0.25], p=NS. Similar proportions of subjects achieved HbA1c<7% (IDeg: 47%; IGlar: 53%; p=NS). FPG reductions were greater with IDeg: 3.6 vs 3.2 mmol/L; ETD: −0.38 mmol/L [–0.70; –0.06]; p=0.02. Overall confirmed hypoglycaemia rates (PG<3.1 mmol/L or severe) were similar (1.72 [IDeg] vs 2.05 [IGlar] episodes/pt-yr; estimated rate ratio [ERR] IDeg/IGlar: 0.84 [0.68; 1.04]; p=NS). Nocturnal confirmed hypoglycaemia rates were significantly lower with IDeg (0.27 vs 0.46 episodes/pt-yr; ERR: 0.57 [0.40; 0.81]; p<0.01). Severe hypoglycaemia was infrequent but significantly lower (43%) with IDeg (0.01 vs 0.02 episodes/pt-yr; ERR: 0.31 [0.11; 0.85]; p=0.02). Mean daily basal insulin doses were 0.63 U/kg for IDeg and IGlar. Weight increases (IDeg: 2.7 kg; IGlar: 2.4 kg) and adverse event rates (3.6 vs 3.4 events/pt-yr) were similar. Degludec safely and effectively improves long-term glycaemic control with a lower risk of nocturnal and severe hypoglycaemia compared with glargine.
STUDY ASSESSING THE COMMUNITY INTERVENTION PROGRAM ON PHYSICAL ACTIVITY IN OBESE AND OVERWEIGHT PATIENTS (PROJECT INTERVOB)
1 , C. Abeledo 2 , P. Lois 1 , C. Villoslada 1 , V. Romo 5
1 SERGAS, Pontevedra, Spain; 2 Department of Mathematics, University of Vigo, Pontevedra, Spain; 3 Head of Department, University of Vigo, Pontevedra, Spain
Objectives: To evaluate the association between regular physical exercise through a community intervention program and health status in obese and overweight patients in the Northern Area of Pontevedra. Methods: To solve the problem posed in this paper, we use traditional methods of assessing physical activity (IPAQ questionnaire and accelerometer), a questionnaire for assessing quality of life of patients (SF-12) and most common clinical parameters (weight, height, BMI .) There will be a descriptive analysis, linear correlation analysis and analysis of crude association (Maentel-Haenszel). Results: The results obtained in this study show that intervention in the community achieved a reduction in weight, BMI and AC. Abdominal circumference decreased by 10 cm in the intervention group versus 4.5 cm in the control cases, whereas weight loss was greater in the control group than in the intervention group, so in these patients decreased by an average of 4.75Kg compared with the control group than lost 2.25kg. IPAQ questionnaire results show a subjective increase in PA in the intervention group of 2584 mets-week versus decreased 383 mets-weeks in the intervention group. Right now, we only have the descriptive analysis, hoping to have the final results before the date of presentation at the conference. Conclusions: Obesity in Spain is a social problem that requires emergent response and intervention strategies designed for this purpose. To prevent the
continued increase in overweight it is necessary to address those factors influencing it, which are modifiable. This includes design strategies that are able to change some lifestyles, like lack of physical activity and sedentary behavior.
HIGH MULTIVITAMIN INTAKE DURING PREGNANCY MODIFIES BRAIN NEUROCIRCUITS REGULATING ENERGY HOMEOSTASIS RESULTING IN OBESE MALE WISTAR OFFSPRING
D. Sanchez-Hernandez, C.E. Cho, S. Reza-Lopez, A. Poon, R. Kubant, J. Wang, P. Huot, G.H. Anderson
Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
Maternal over consumption of micronutrients during critical windows of development lead to increased risk of obesity in the offspring in later life. Fortification policies and increased use of vitamin supplements by women of childbearing age lead to intakes greater than recommended. We have shown, high multivitamin (10-fold AIN-93G levels, HV) intake by Wistar rats during pregnancy results in increased body weight (BW) in offspring weaned to a regular vitamin (RV) diet. However, the mechanisms by which this phenotype develops have yet to be elucidated. We hypothesized that the brain‟s neurocircuits that control energy homeostasis play a role in the development of obesity. Pregnant Wistar rats were fed either the RV or HV during pregnancy. BW and mRNA levels of genes involved in energy homeostasis were measured at birth, weaning and 29 weeks post-weaning in male offspring. BW of pups from dams fed the HV diet were greater compared to pups from RV fed dams (p < 0.05). The mRNA levels of hypothalamic pro-opiomelanocortin (POMC) in HV pups were ~54% (p<0.05) and ~30% (p<0.05) lower than in RV pups at birth and post-weaning respectively. Dopamine receptor 5 mRNA levels in the hippocampus were ~22% (p<0.05) and ~54% (p<0.05) higher at birth and weaning, respectively, in HV versus RV pups. These results indicate that the increased prevalence of obesity may have its origins in the effect of diets during pregnancy on development of neurocircuits regulating energy homeostasis. (Supported by the Canadian Institutes of Health and Research).
CANAGLIFLOZIN COMPARED TO SITAGLIPTIN IN SUBJECTS WITH TYPE 2 DIABETES ON METFORMIN AND SULFONYLUREA
1 , J. Gross 2 , M. Fu 3 , J. Yee 3 , M. Kawaguchi 3 , W. Canovatchel 3 , G. Meininger 3
Rudolfstiftung Hospital, Vienna, Vienna, Austria; 2 Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; 3 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
Canagliflozin (CANA), a novel sodium glucose co-transporter 2 (SGLT2) inhibitor, is being developed for the treatment of type 2 diabetes mellitus (T2DM). In this randomized, double-blind, active-controlled, Phase 3 study, subjects with T2DM inadequately controlled with metformin (MET) + sulfonylurea (SU) (N=755; age 56.7 years; A1C, 8.1%; body mass index, 31.6 kg/m2) received CANA 300 mg or sitagliptin (SITA) 100 mg once daily. At 52 weeks, CANA 300 mg demonstrated both non-inferiority and superiority to SITA 100 mg in lowering A1C (–1.03% vs –0.66%, respectively). CANA significantly reduced body weight and improved fasting plasma glucose and systolic blood pressure compared with SITA (P<0.001 for all), and showed numerical improvement in high-density lipoprotein cholesterol and a slight increase in low-density lipoprotein cholesterol. The overall incidence of adverse events (AEs) was similar with CANA (76.7%) and SITA (77.5%). Rates of serious AEs (6.4% vs 5.6%) and AE-related discontinuations (5.3% vs 2.9%) were similar for CANA and SITA. Incidences of AEs consistent with genital mycotic infections were higher with CANA than SITA in women (15.3% vs 4.3%) and men (9.2% vs 0.5%). Incidences of urinary tract infections (4.0% vs 5.6%) and osmotic diuresis-related AEs (eg, pollakiuria; <2% per specific AE), and the proportion of subjects with ≥1 hypoglycemia episode (43.2% vs 40.7%) were similar for CANA and SITA. In summary, CANA showed improvements in glycemic control and reduced body weight and systolic blood pressure compared with SITA, and was well tolerated in subjects with T2DM inadequately controlled with MET + SU.
GLP-1, GIP AND GLUCAGON LEVELS DYNAMICS IN HIGH RISK NON-DIABETIC SUBJECTS FOLLOWING OGTT
E.A. Shestakova, A.V. Ilyin, M.V. Shestakova, I.I. Dedov
Endocrinology Research Centre, Moscow, Russia
Background and aims: Recent trials showed that GLP-1 release is suppressed in T2DM, but little is known about the incretin system in subjects with diabetes risk factors. We studied the change in incretin-hormones secretion under carbohydrate load in non-diabetic subjects. Materials and methods: Oral glucose tolerance test (OGTT) was performed in 53 high-risk subjects, mean age 58±11,9. According to OGTT 11 persons had normal glucose tolerance (NGT), 14 - impaired glucose tolerance (IGT), 28 - T2DM. Based on BMI all the subjects were stratified into 3 groups (< 30, 30-34,9 , > 35 kg/m2). Fasting and peak levels of GPP-1, glucagon and GIP were measured during the OGTT. The difference between peak and fasting incretin levels (Δ) were analyzed. Results: Plasma GLP-1 and GIP levels increased while plasma glucagon level decreased in all groups during OGGT. Δ GLP-1 was less in IGT and T2DM vs. NGT (+0,15±0,08 vs. +0,15±0,05 vs. +0,28±0,1 ng/ml respectively). Similar Δ GIP was less in IGT and T2DM vs. NGT. Magnitude of glucagon reduction was similar in IGT and T2DM (-0,28±0.1 vs -0,2±0,1 ng/ml respectively), and negligible in NGT (-0,03±0,016 ng/ml). BMI subgroups did not significantly differ in Δ GLP-1 and Δ glucagon, but differed in Δ GIP: it progressively decreased with higher BMI (0,37±0,11 vs. 0,24±0,09 vs. 0,19±0,1 ng/ml, respectively). Conclusions: We confirmed that incretin-hormones secretion defect after carbohydrate load starts much earlier than T2DM debuted. The role of GIP secretion in obesity should be elucidated.
CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS CONTROLLED PRIMARY HEALTH CARE
L. Sierra-Martínez, R. Martínez-Fuerte
Valladolid Este Primary Assistance Gerency, Valladolid, Spain
Objective: To determine the prevalence of other Cardiovascular Risk Factors (CRF) present in patients with controlled type 2 Diabetes Mellitus (DM2) in Primary Health Care. To provide comprehensive and continuous care. Methodology: The authors conducted a cross sectional study applied to selected patients (n = 104, 52 males (M) and 52 women (W)) chosen by non-probability sampling in a row, among Type 2 Diabetic patients attending our clinic included in the Service Care for diabetic patients Portfolio Services Primary Sacyl. They made history of presence / absence of a history of Hypertension, Dyslipidemia, Smoking, Overweight / Obesity and Physical inactivity Data are collected in an Excel spreadsheet and analyzed using SPSS 9.0 for Windows. Results: 1-DM2 patients age: 90-95 (1M, 0W), at 85-90 (1M, 2W), 80-85 (7M, 5W), 75-80 (7M, 7W), 70 - 75 a (4M, 11W), 65-70 (10M, 10W), 60-65 (16M, 9W), 55-60 (2M, 3W), 50-55(4M,5W). 2-Prevalence of: - Arterial Hypertension (AH): 58.6% (60 patients, 29 M, 31 W), Dyslipidemia: 50% (52 patients, 27 M, 25 W), Smoking: 19.23% (20 patients, 12 men, 8 women), Overweight / Obesity: 48% (50 patients, 23 M, 27 W), Sedentary lifestyle: 23.07%(24 patients, 12 M, 12 W). Conlusions: We conclude that 58.6% of diabetic patients have a history of Hypertension, 50% have Dyslipidemia, 19.23% are Smoking, 48% have Overweight / Obesity and Sedentary present 23.07%. Therefore you must implement an improvement plan of care by developing prevention, promotive, curative and rehabilitation of CRF associated with diabetes from Primary Care.
COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES IN PRIMARY CARE OF CASTILLA Y LEON SPAIN
L. Sierra-Martínez, R. Martínez-Fuerte
Valladolid Este Primary Assistance Gerency, Valladolid, Spain
Aims: To determine the complications presented by patients with controlled type 2 diabetes in primary health care. To provide comprehensive and continuous care. Methodology: The authors conducted a cross sectional study applied to selected patients (n = 104, 52 men (m) and 52 women (w)) chosen by non-probability sampling in a row, among type 2 diabetic (DM2) patients attending our clinic included in the Service Care for Diabetic patients Portfolio Services Primary Sacyl. They made assessment of presence / absence of complications. Data are collected on a Excel spreadsheet and analyzed using SPSS 9.0 for Windows. Results: 1-DM2 patients age: 90-95(1m,0w), 85-90 (1m, 2w), 80-85 (7m, 5w), 75-80 (7m, 7w), 70-75(4m,11w),65-70(10m,10w), 60-65 (16m, 9w), 55-60(2m-, 3w), 50-55 (4m, 5w). 2-Acute Complications: Hypoglycemia (Women-5,79%;Men-5,79%). Hyperglycemia (Women-1,93%,Men-1,93%). 3- Chronic Complications: 3.1-microvascular: retinopathy-(Women-1,93%,Men-1, 93%). -Neuropathy (Women-0%; Men-3, 85%). -Erectile Dysfunction (Men-5,79%). - Ulcers and/or Amputation (Women-7, 79%; Men-5, 79%). 3.2-Macrovascular:-Cardiovascular Diseases (Women-3, 85% Men-19,23%). Cerebrovascuar Disease (Women-0%;Men-7,69%).-Peripheral Arteriopathy (Women-15,38%;Men-9,62%). Conclusions: We conclude that 7.62% of women and men with Diabetes had Acute Complications, Chronic Complications but in 28.85% of women with Diabetes face a 53.90% of Diabetic men. Therefore it must implement a Plan of care improvement of response to the physical, psychological and social activities through the development of preventive, promotive, curative and rehabilitation from the Primary Care.
DOES SHORT-TERM VERY LOW CALORIE DIET HAVE POSITIVE EFFECT ON ENDOTHELIAL ACTIVATION IN OBESE TYPE 2 DIABETIC PATIENTS?
J. Skrha Jr.
1,2 , M. Prazny 1 , J. Soupal 1 , T. Stulc 1 , L. Landova 2 , J. Kvasnicka 2 , M. Jarolimkova 1 , J. Skrha 1 , M. Kalousova 2
3rd Dept. of Internal Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; 2 Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic
The aim of this study was to evaluate the effect of two-week very low calorie diet (VLCD) in obese patients (BMI>35 kg/m2) on oxidative stress, endothelial activation and soluble receptor for advanced glycation endproducts (sRAGE). Total of 23 severely obese patients (13 with Type 2 diabetes mellitus /T2DM/, BMI 55±11 kg/m2; 10 controls without diabetes, BMI 48±7 kg/m2) were hospitalized for two weeks on VLCD (2500 kJ/day) and biochemical parameters, markers of oxidative stress, endothelial activation, sRAGE and metalloproteinases were analyzed before and after the dietary regimen. Significant weight reduction was observed after 2 weeks of VLCD in both diabetic (10±5 kg, p<0.0005) and non-diabetic obese patients (10±3 kg, p<0.0005). This was associated with significantly decreased malondialdehyde in both T2DM (p<0.005) and controls (p<0.05). Significant reduction of vWF and E-selectin (p<0.05) was found in both groups. Similarly, sRAGE concentration was mildly decreased in both diabetic (791 ± 378 vs. 702±238 μmol/l) and non-diabetic patients (777±333 vs. 719±281 μmol/l), but the difference did not reach statistical significance. Strong association of sRAGE and PAI-1 (r=0.67, p<0.05), E-selectin (r=0.62, p<0.05) and ICAM-1 (r=0.57, p<0.05) was observed in obese T2DM before and after VLCD administration. In our study, weight reduction after two weeks of VLCD in both severely obese diabetic and non-diabetic patients was associated with decreased oxidative stress and endothelial activation. Strong relationship of sRAGE with parameters of activated endothelium both before and after weight reduction supports the idea that RAGE pathway is associated with endothelial changes.
CANAGLIFLOZIN IMPROVES GLYCEMIA IN TYPE 2 DIABETES SUBJECTS POORLY CONTROLLED WITH DIET AND EXERCISE
1 , W.T. Cefalu 2 , C. Tong 3 , S. Sha 3 , J. Yee 3 , M. Alba 3 , W. Canovatchel 3 , G. Meininger 3
Clinical Trial Center, Sahlgrenska University Hospital, Gothenburg, Sweden; 2 Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America and LSUHSC School of Medicine, New Orleans, Louisiana, United States of America; 3 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
Canagliflozin (CANA) is a sodium glucose co-transporter 2 inhibitor in development for the treatment of type 2 diabetes mellitus (T2DM). In this randomized, double-blind, placebo (PBO)-controlled, Phase 3 study, subjects with T2DM inadequately controlled with diet and exercise (N=584; age, 55.4 years; A1C, 8.0%; BMI, 31.6 kg/m2) received CANA 100 or 300 mg or PBO. At 26 weeks, CANA 100 and 300 mg significantly reduced A1C compared with PBO (–0.77%, –1.03%, and 0.14%, respectively; P<0.001 for both); CANA also improved fasting plasma glucose and 2-hour postprandial glucose compared with PBO (P<0.001 for all). Both CANA doses reduced body weight, decreased systolic blood pressure, and increased high-density lipoprotein cholesterol (P<0.01 for all), with a small, dose-related increase in low-density lipoprotein cholesterol. Incidences of adverse events (AEs) were modestly higher with CANA 100 and 300 mg than PBO (61.0% and 59.9% vs 52.6%); serious AE and AE-related discontinuation rates were low across groups. Incidences of AEs consistent with genital mycotic infections were higher with CANA 100 and 300 mg than PBO (women, 8.8% and 7.4% vs 3.8%; men, 2.5% and 5.6% vs 0%). CANA 100 and 300 mg showed slightly higher rates than PBO of UTIs (7.2% and 5.1% vs 4.2%) and osmotic diuresis-related AEs (eg, pollakiuria; ≤3% per specific AE); these were generally mild and led to few discontinuations. Incidences of hypoglycemia were similar across groups. In summary, CANA significantly improved glycemic control, reduced body weight, and was well tolerated in subjects with T2DM inadequately controlled with diet and exercise.
PREVALENCES OF HYPERLIPIDEMIAS AND ASSOCIATIONS WITH OBESITY IN RURAL CHINESE HYPERTENSIVE: YUHUAN RURAL HEALTH POPULATION COHORT STUDY
1 , C.W. Fu 3 , S.T. Li 1 , X.B. Ye 2 , N. He 3 , Q.W. Jiang 3
Yuhuan County Center of Disease Control and Prevention, Zhejiang Province, China; 2 Health Burea of Yuhuan County, Zhejiang Province, China; 3 School of Public Health, Fudan University, Zhejiang Province, China
Objective: To explore the prevalence of hyperlipidemia and the relationship with overweight/obesity in hypertensive adults in rural Yuhuan, China. Method: A cross-sectional study was carried out as a baseline study of Rural Yuhuan Health Population Cohort in all rural communities in Yuhuan County, China. A total of 33963 subjects aged 35 years old or above were diagnosed as hypertension and included into the analysis. Hyperlipidemia was defined as blood triglyceride >=1.7mmol/l and/or total cholesterols>=5.17mmolo/l. Body mass index (BMI) was grouped into normal weight (<25.0), overweight (25.0-29.9) and obesity (>=30.0). Nominal logistic model was used in SPSS 16.0. Result: Among 33693 subjects, the prevalences of only hypercholesterolemia, only hypertriglyceridemia, both hypercholesterolemia and hypertriglyceridemia, and hyperlipidemia were 27.7%, 13.2%, 20.1% and 29.8%, respectively. These prevalences were higher in subjects with overweight/obesity than in those with normal weight significantly (χ2
＝ 1087.12, p<0.001). In nominal logistic model, results showed that BMI were significantly associated with only hypercholesterolemia, only hypertriglyceridemia, and both (odds ratios and 95% confidential interval were 1.02 and 1.02-1.03, 1.12 and 1.11-1.13, 1.13 and 1.12-1.14, respectively) and obesity and overweight were possible risk factors of them (odds ratios and 95% confidential interval were 1.03 and 0.92-1.16, 2.26 and 1.98-2.57, 2.49 and 2.22-2.79 for obesity, and 1.13 and 1.06-1.19, 1.96 and 1.82-2.11, 2.12 and 1.99-2.26 for overweight, respectively) after the adjustment of covariates such as age, gender, etc. Conclusion: Hyperlipidemia, especial hypercholesterolemia, was common in rural hypertensive Chinese aged 35 years old or above and overweight/obesity were their possible risk factors.
PREVALENCE AND RISK FACTORS OF HIGH-NORMAL BLOOD PRESSURE OF CHONGWEN DISTRICT IN BEIJING
, S.Q. Cui, X.Q. Lu, Z.H. Sun, A.M. Guo
School of Public Health and Family Medicine, Capital Medical University, Beijing, China
Objective: The use of community health diagnosis data of Chongwen District in Beijing analysis high-normal blood pressure value epidemiological characteristics and the related risk factors for hypertension early prevention, provides the basis. Methods: Application form on the questionnaire to above the age of 18 people cross-sectional survey, 13620 people were surveyed, the application of the Logistic analysis method, and the related risk factors for high-normal blood pressure. Results: The aged 18 or above high-normal blood pressure for 29.1% detection rate, hypertension prevalence rate was 31.3%, many factors analysis shows that, age, smoking, alcohol consumption, high salt, waist circumference, BMI, diabetes is a high value of high-normal blood pressure risk factors, and women, education and labor intensity, soy intake, sleep is good protection factor. Conclusion: The high-normal blood pressure detection rate of Chongwen District in Beijing of is higher and is related with various risk factors. We should improve the living ways to reduce the incidence of high-normal blood pressure.
ANTI-OBESITY EFFECT OF DEHYDROEPIANDROSTERONE: FEASIBLE INVOLVEMENT OF 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITION IN RODENT ADIPOSE TISSUE
, Y. Kobayashi
Kobe Pharmaceutical University, Japan
Dehydroepiandrosterone (DHEA) has been suggested to have an anti-obesity effect; however, the mechanism underlying this effect remains unclear. The effect of DHEA on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis. The key to the intracellular activation of glucocorticoids in adipocytes is 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from an inactive 11-keto form (cortisone in humans and 11-dehydrocorticosterone in rodents). In humans and rodents, intracellular glucocorticoid reactivation is exaggerated in obese adipose tissue. Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited about 15.6% of 11beta-HSD1 activity at a concentration of 1 uM within 10 min. Inhibition was also observed in a cell-free system composed of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11beta-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11beta-HSD1. Moreover, conversion from DHEA to estrogens was not observed by sensitive semi-micro HPLC equipped with electrochemical detector. These results indicate that the inhibition of 11beta-HSD1 by DHEA depends on neither the transcriptional pathway nor the nonspecific manner. This is the first demonstration that the anti-obesity effect of DHEA is exerted by nontranscriptional inhibition of 11beta-HSD1 in rodent adipocytes.
CANAGLIFLOZIN REDUCES BODY WEIGHT MAINLY THROUGH LOSS OF FAT MASS IN SUBJECTS WITH TYPE 2 DIABETES
1 , W.T. Cefalu 2 , J. Xie 3 , D. Sullivan 3 , K. Usiskin 3 , W. Canovatchel 3 , G. Meininger 3
Reduce, A Research Clinic, Vipperød, Denmark; 2 Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America and LSUHSC School of Medicine, New Orleans, Louisiana, United States of America; 3 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
Canagliflozin (CANA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, improves glycemia and reduces body weight in subjects with type 2 diabetes mellitus (T2DM). The relative contributions of weight loss from fat and lean mass were determined in a subset of T2DM subjects enrolled in 2 randomized, double-blind, Phase 3 studies. Study 1 (52-week) compared CANA 100 and 300 mg with glimepiride (GLIM) in subjects on background metformin (N=1,450; age, 56.2 years; A1C, 7.8%; body weight, 86.6 kg). Study 2 (26-week) compared CANA 100 and 300 mg with placebo (PBO) in subjects on various antihyperglycemic agents (N=714; age, 63.6 years; A1C, 7.7%; body weight, 89.5 kg). Body composition was assessed by DXA in Studies 1 (n=208) and 2 (n=211); abdominal fat distribution was assessed by CT scans only in Study 1 (n=217). In Study 1, CANA 100 and 300 mg reduced body weight compared with GLIM (–4.4, –4.2, and 0.8 kg, respectively; P<0.001), with fat mass loss accounting for two-thirds of the overall reduction. Both CANA doses reduced percent total fat (fat percentage of total weight) compared with GLIM. CANA showed slightly greater reductions in visceral than subcutaneous abdominal adipose tissue compared with GLIM. In Study 2, CANA 100 and 300 mg reduced body weight compared with PBO (–2.5, –3.2, and –0.2 kg, respectively; P<0.001), with greater loss from fat than lean mass; CANA also reduced percent total fat compared with PBO. In summary, body weight reductions with CANA in T2DM subjects were predominantly from loss of fat mass.
ASSOCIATION OF VITAMIN D3 LEVELS AND OBESITY IN TYPE 2 DIABETICS
Clinic for endocrinology and Diabetes, Clinical Center of University of Sarajevo, Bosnia and Herzegovina
Obesity is a risk factor for many somatic and psychological disorders, including cardiovascular disease, type 2 diabetes mellitus, osteoarthritis and several cancer types. Vitamin D is stored in adipose fat tissues, making it unavailable for the body to use; as a result, people who are overweight are already more likely to have low levels of serum vitamin D. Vitamin D deficiency is associated with multiple health conditions including diabetes, cardiovascular diseases including stroke, depression, dementia and other conditions. Methods: The 25(OH)D3 status was analyzed in a population of 90 type 2 diabetics (50 female and 40 male) at Clinic for Endocrinology and Diabetes in Sarajevo. Patients were divided by age (<50 years and ≥0 years) and BMI (<25kg/m2 and >25kg/m2). Measurements of vitamin D3, basal insulin, fasting glucose, CRP and lipid profile were used on all patients. Referral levels of vitamin D3 were 20-56ng/ml. Vitamin D deficiency was defined as 25OHD≤0ng/ml and vitamin D insufficiency as 25OHD≤0ng/ml. Results: The prevalence of vitamin D deficiency was highest in individuals with highest BMI. For both sexes and both age groups there was a significant decrease of serum 25(OH)D3 levels with increasing BMI. Median vitamin D level in obese diabetics was 15.7 (4–36.7)ng/ml. The 25(OH)D3 level depends on BMI. HOMA-IR was in negative correlation with vitamin D3 level. Conclusion: Obesity and low levels of vitamin D are both associated with a diagnosis of Type 2 diabetes and their combination may put diabetics at even greater risk of insulin resistance than either factor alone.
OBESITY AND METABOLIC SYNDROME AS RISK FACTORS FOR COMMUNITY-ACQUIRED PNEUMONIA
1 , J. Montserrat-Capdevila 1 , M. Falguera 2 , N. Miró 1 , M. Rodríguez 1 , R. Llovet 1 , M. Calderó 1 , M. Falguera 1 , G. Pascual 1 , J. Sangrà 1 , V. Sanchez 1 , M. Pena 1
Pla Urgell Primary Care Area, Mollerussa, Spain; 2 Arnau de Vilanova Hospital, Lleida, Spain
Objective: To evaluate the potential association between body mass index (BMI), waist circumference (WC) and metabolic syndrome (MS), and development of community-acquired pneumonia (CAP). Methods: A population-based case-control study. All patients aged >=18 years diagnosed as having CAP in the Emergency Department between January 2009 and March 2010 were prospective collected. Cases were matched by age and sex with control subjects randomly selected from a Primary Care Area. Anthropometric and metabolic characteristics, comorbidities and treatments were recorded. Subjects were stratified by BMI and divided into five categories according to the World Health Organization classification. MS was defined by the National Cholesterol Education Program Adult Treatment Panel III 2001 (NCEP-ATP III). Univariate and multivariate analyses were performed with adjustment for confounding factors. Results: 164 cases and 164 controls (102 men and 62 women in each group, mean age 68 years) were enrolled. In the multivariate analysis, COPD (Odds ratio [OR] 6.40; 95% confidence interval [CI] 2.95-13.90) and MS (OR 2.00; 95% CI 1.11-3.61) were significantly associated with an increased risk of CAP; conversely, pneumococcal vaccine (OR 2.00; 95% CI 0.29-0.80) and ACE inhibitors treatment (OR 0.51; 95% CI 0.27-0.94) were identified as protective factors. Neither subgroups of patients according to the BMI nor WC showed association with development of CAP. Conclusions: Our study suggests that there is not a relation between BMI subgroups or WC and development of CAP. However, MS, in addition to other well-recognized predictive factors, could be a significant risk factor for CAP.
CANAGLIFLOZIN IMPROVES GLYCEMIA IN SUBJECTS WITH TYPE 2 DIABETES ON METFORMIN PLUS SULFONYLUREA
1 , C. Mathieu 2 , L. Deng 3 , S. Black 3 , F. Vercruysse 4 , W. Canovatchel 3 , G. Meininger 3
University of Liverpool, Liverpool, United Kingdom; 2 KULeuven, Leuven, Belgium; 3 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America; 4 Janssen Research & Development, Beerse, Belgium
Canagliflozin (CANA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is in development for the treatment of type 2 diabetes mellitus (T2DM). This randomized, double-blind, placebo (PBO)-controlled, Phase 3 study evaluated CANA 100 or 300 mg compared with PBO in subjects with T2DM on metformin (MET) + sulfonylurea (SU) (N=469; age 56.7 years; A1C, 8.1%; body mass index, 33.0 kg/m2). At 26 weeks, A1C was significantly reduced with CANA 100 and 300 mg compared with PBO (–0.85%, –1.06%, and –0.13%, respectively; P<0.001 for both). Both CANA doses significantly improved fasting plasma glucose and reduced body weight compared with PBO (P<0.001 for all). CANA showed non–dose-dependent trends toward improvement in systolic blood pressure, high-density lipoprotein cholesterol, and triglycerides; a small increase in low-density lipoprotein cholesterol was observed with CANA 300 mg. Incidences of overall adverse events (AEs) were similar across groups (57.3%, 62.2%, and 64.1%, respectively, for CANA 100 and 300 mg and PBO); rates of serious AEs and AE-related discontinuations were low. CANA 100 and 300 mg showed higher rates than PBO of hypoglycemia (27.4%, 30.1%, and 15.4%, respectively) and AEs consistent with genital mycotic infections (women, 14.8% and 17.4% vs 5.0%; men, 6.6% and 3.4% vs 1.3%). Incidences of osmotic diuresis-related AEs were low, but numerically higher with CANA (<3% per specific AE). Rates of urinary tract infections were similar across groups. In summary, CANA significantly improved glycemic control and reduced body weight, and was well tolerated in subjects with T2DM inadequately controlled with MET + SU.
EFFECTS OF THE SGLT2 INHIBITOR DAPAGLIFLOZIN BEYOND GLUCOSE REDUCTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
1 , E. Hardy 2 , A. Ptaszynska 3 , S. Parikh 2
University of Manitoba, Winnipeg, MB, Canada; 2 AstraZeneca, Wilmington, Delaware, United States of America; 3 Bristol-Myers Squibb, Princeton, New Jersey, United States of America
Dapagliflozin, a selective SGLT2 inhibitor that promotes urinary glucose excretion, reduces hyperglycaemia in patients with type 2 diabetes mellitus. Excretion of glucose also results in a loss of calories and mild osmotic diuresis, which lead to additional effects, including weight loss and blood pressure reduction. Changes in cardiovascular risk factors, including body weight, blood pressure, lipids, and uric acid were assessed in > 4000 patients across a broad phase 3 programme. Adjusted mean body weight reductions of 0.46–2.16 kg with dapagliflozin compared to placebo were observed across the phase 3 studies. The weight loss was sustained over at least 2 years, and a body composition study indicated that the weight effect was primarily due to a reduction in body fat mass. Reductions in mean blood pressure with dapagliflozin compared to placebo (–0.5 to –7.2 for SBP and –0.2 to –3.5 for DBP) were also observed across the phase 3 studies and were consistent with a mild osmotic diuresis. This reduction in blood pressure was more pronounced in patients with baseline SBP > 140 mmHg. Measured orthostatic hypotension occurred with similar frequency in the dapagliflozin and control groups. No consistent changes in lipid measurements were observed across the phase 3 studies. Uric acid, a potential marker of cardiovascular and renal risk, was consistently reduced across studies with dapagliflozin compared with placebo (–0.30 to –1.04 mg/dL). These secondary, non-glycemic effects of dapagliflozin suggest a trend for overall improvement in markers of cardiovascular risk.
EFFICACY AND SAFETY OF CANAGLIFLOZIN IN SUBJECTS WITH TYPE 2 DIABETES WITH MODERATE RENAL IMPAIRMENT
1 , M. Davies 2 , D. de Zeeuw 3 , G. Bakris 4 , K. Usiskin 5 , C. Gassmann-Mayer 6 , G. Meininger 5
1 University of Manitoba, Winnipeg, Canada; 2 University of Leicester, Leicester, United Kingdom; 3 University Medical Centre Groningen, Groningen, Netherlands; 4 University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States of America; 5 Janssen Research & Development, LLC, Raritan, New Jersey, United States of America; 6 Janssen Research & Development, LLC, Titusville, New Jersey, United States of America
Efficacy and safety of canagliflozin (CANA), a sodium glucose co-transporter 2 inhibitor, were evaluated in type 2 diabetes mellitus (T2DM) subjects with moderate renal impairment (baseline eGFR≥0 and <60mL/min/1.73m2) using pooled data from 4 randomized, double-blind, placebo (PBO)-controlled, Phase 3 studies. Subjects (N=1,085; mean age, 67.1y; HbA1c, 8.1%; eGFR, 48.2mL/min/1.73m2; weight, 90.9kg) received CANA 100mg (n=338), CANA 300mg (n=365), or PBO (n=382). At Week 18 (1 study) and Week 26 (3 studies), CANA 100 and 300mg significantly reduced HbA1c (PBO-subtracted LS mean change [LOCF],–0.38%, –0.47% [P<0.001]) and body weight (PBO-subtracted LS mean percent change [LOCF], –1.6%, –1.9% [P<0.001]). In subjects with baseline eGFR<45mL/min/1.73m2 (n=364), CANA 100 and 300mg significantly reduced HbA1c (–0.23% [P=0.044], –0.39% [P<0.001]) and body weight (–1.2% [P=0.001], –1.8% [P<0.001]) relative to PBO, but with lesser magnitude than in subjects with eGFR≥5mL/min/1.73m2 (n=721; HbA1c: –0.47%, –0.52% [P<0.001] and body weight: –1.8%, –2.0% [P<0.001]). Adverse event (AE) rates were slightly higher with CANA 100 and 300mg (74.0%, 75.3%) compared with PBO (70.4%). Serious AEs were more frequent with PBO (19.6%) than CANA 100 or 300mg (13.3%, 14.8%); AE-related discontinuations were low across groups. AEs related to reduced intravascular volume were higher with CANA 100 and 300mg (8.5%, 5.0%) than PBO (2.6%), but led to few discontinuations. Incidences of renal-related AEs that led to discontinuation or were serious were similar across groups. In conclusion, CANA showed clinically meaningful reductions in HbA1c and weight and was generally well tolerated in T2DM subjects, even those with compromised renal function.
LONG-TERM EFFECTIVENESS OF DAPAGLIFLOZIN OVER 104 WEEKS IN PATIENTS WITH T2DM INADEQUATELY CONTROLLED WITH INSULIN
1 , J. Wilding 2 , K. Rohwedder 3 , J.E. Sugg 4 , S.J. Parikh 4
1 University of Manitoba, Winnipeg, Canada; 2 University of Liverpool, Liverpool, United Kingdom; 3 AstraZeneca, Wedel, Germany; 4 AstraZeneca Pharmaceuticals, Wilmington, Delaware, United States of America
Dapagliflozin (DAPA) is a selective SGLT2 inhibitor that increases urinary glucose excretion and reduces hyperglycaemia in T2DM independent of insulin (INS) secretion. Here, we report results at Week 104 of a double-blind study of patients with T2DM inadequately controlled with INS (N=808; mean baseline HbA1c 8.53%). Patients were randomised to placebo (PBO) or DAPA 2.5, 5, 10mg/day added to INS (mean baseline INS 77 IU/day) ± oral glucose lowering drugs (NCT00673231). Analyses at Week 24 and Week 48 were reported previously. At Week 48, patients on DAPA 5mg/day were switched to 10mg/day as per the study design (5/10 group). INS was uptitrated if HbA1c was >7.5% during Weeks 52–65 or >7.0% during Weeks 78 to 104. Week 104 analyses used observed cases and included data after INS uptitration. Overall, 63.6% of patients completed the study. At Week 104, mean HbA1c change from baseline was -0.43% (PBO) and -0.64% to -0.82% (DAPA). With PBO, mean INS dose increased by 18.3 IU/day and weight increased by 1.8kg. With DAPA, INS dose was stable (-0.8 to 4.1 IU/day) and weight decreased by 0.9 to 1.4kg. Adverse events, including total hypoglycaemia, were similar across groups. The frequency of events suggestive of genital infection (GenInf) and urinary tract infection (UTI) were higher with DAPA vs PBO (GenInf: 7.4 to 14.3% vs 3.0%; UTI: 8.4 to 13.8% vs 5.6%) but most occurred before Week 24 as single episodes. In summary, DAPA produced long-term reductions in HbA1c and weight, with no escalation of INS dose.
USEFULNESS OF HBA1C IN SCREENING FOR DIABETES MELLITUS: EVIDENCE FROM AN URBAN SRI LANKAN COMMUNITY
1 , A. Pathmeswaran 1 , S. Chackrewarthy 1 , N. Kato 2 , A.R. Wickremasinghe 1
Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka; 2 National Center for Global Health and Medicine, Tokyo, Japan
Objective: To determine the usefulness of newly adopted glycated haemoglobin (HbA1C) criterion in screening an urban Sri Lankan community for diabetes. Methods: A cross sectional study was conducted in an urban health administrative area in Sri Lanka involving individuals aged 35-64 years, selected by stratified random sampling. Anthropometric and clinical data were recorded. Blood samples were collected for HbA1C, fasting plasma glucose (FPG) and lipid profile. HbA1C was measured by National Glycohaemoglobin Standardization Program certified Bio Rad Variant HPLC method. American Diabetes Association recommended FPG and HbA1C criteria were used for analysis. Previously diagnosed diabetics were excluded. Results: 2516 subjects were studied (Females - 53.8%; Mean [SD] age - 52 [7.9] years). 245 (9.7%) had FPG ≥26mg/dl. 173 (6.9%) had HbA1C ≥.5%. Concordance between FPG and HbA1C was seen in 95.1%. Compared to FPG, HbA1C had a sensitivity of 60% (95% CI 53.6-66.2), and specificity of 98.9% (95% CI 98.3-99.3). The positive and negative predictive values were 85% (95% CI 78.8-89.9) and 95.8% (95% CI 94.9-96.6), respectively. Subgroup analysis based on cardiovascular risk factors (gender, age, hypertension, body mass index, smoking, dyslipidaemia) did not reveal any significant difference in positive predictive value but the sensitivity was higher with triglyceride ≥50mg/dl (p=0.009). Conclusions: HbA1C ≥.5% as a criterion to screen for diabetes has a high specificity but sensitivity is moderate in this urban Sri Lankan community. The HbA1C criterion identifies 30% fewer cases of undiagnosed potential diabetes than the FPG criterion and this is comparable to data from other countries.
UTILITY OF HBA1C IN DETECTING IMPAIRED FASTING GLYCAEMIA: EVIDENCE FROM AN URBAN SRI LANKAN COMMUNITY
1 , A. Pathmeswaran 1 , S. Chackrewarthy 1 , N. Kato 2 , A.R. Wickremasinghe 1
1 Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka; 2 National Center for Global Health and Medicine, Tokyo, Japan
Objective: To determine the usefulness of American Diabetes Association (ADA) recommended glycated haemoglobin (HbA1C) criterion in detecting Impaired Fasting Glycaemia (IFG) in an urban Sri Lankan community. Methods: A cross sectional study was conducted in an urban health administrative area in Sri Lanka involving individuals aged 35-64 years, selected by stratified random sampling. Anthropometric and clinical data were recorded. Blood samples were collected for HbA1C, fasting plasma glucose (FPG) and lipid profile. HbA1C was measured by NGSP certified Bio Rad Variant HPLC method. IFG was defined as FPG 100-125mg/dl or HbA1C 5.7-6.4%. Those with diabetes, FPG ≥26mg/dl or HbA1C ≥.5% were excluded. Results: 2245 subjects were studied (Females - 53.6.%; Mean [SD] age - 51.7 [8.0] years). 1237 (55.1%) had FPG of 100-125mg/dl. 363 (16.2%) had HbA1C of 5.7-6.4%. Concordance between FPG and HbA1C was seen in 53.1%. Compared to FPG, HbA1C had a sensitivity of 22.2% (95% CI 19.8-24.6), and specificity of 91.2% (95% CI 89.2-92.8). The positive and negative predictive values were 75.5% (95% CI 70.7-79.8) and 48.8% (95% CI 46.5-51.1), respectively. Subgroup analysis based on cardiovascular risk factors [gender, age, hypertension, body mass index (BMI), smoking, dyslipidaemia] revealed that the sensitivity was higher in those with age ≥5years (p<0.001) and BMI ≥3kg/m2 (p=0.001). Conclusions: HbA1C of 5.7-6.4% as a criterion to detect IFG has a high specificity but sensitivity is low in this urban Sri Lankan community. The HbA1C criterion identifies 70.7% fewer cases of potential IFG than the FPG criterion. Population based HbA1C criteria are required.
FREQUENCY OF SELECTED NEOPLASIA TYPES AMONG PATIENTS WITH AND WITHOUT DIABETES-RETROSPECTIVE ANALYSIS FROM ONCOLOGY DEPARTMENT-PROVINCE HOSPITAL IN ZIELONA GÓRA , POLAND
1 , E. Sutkowska 2 , B. Iwanowska-Chomiak 1 , P. Myśiwiec 1 , M. Wachowiak 1 , E. Skrzypczak 1 , L. Dęicki 1 , K. Czarny 1 , J. Żrawska 1 , A. Kamińka 1 , K. Sutkowski 3 , J. Lipińki 4
Province Hospital, Lubuski Center of Oncology, Zielona Gora, Poland; 2 Division of Rehabilitation in Department and Clinic of Orthopaedic and Traumatologic Surgery, Wroclaw Medical University, Wroclaw, Poland; 3 First Department and Clinic of General, Gastroenterological and Endocrine Surgery, Wroclaw Medical University, Wroclaw, Poland; 4 University of Zielona Gora, Zielona Gora, Poland
People with diabetes are more prone to certain several types of cancer. The associations between diabetes and cancers may be due to: hyperglycaemia- promote cell cancer growth; hyperinsulinaemia- as insulin is a anabolic hormone and because of common risk factors for diabetes and cancers. We would like to find whether the frequency of selected neoplasia types among patients with diabetes is similar to the neoplasia types among patients without carbohydrate metabolism disturbances. Methods: In our retrospective study we analyzed records of 1363 patients treated at Oncology Department-Province Hospital in Zielona Góra between August 2011-February 2012, because of different neoplasia types: 4.6% ( n=63) with and 95.4% (n=1300) without diabetes. Results: Among the 63 patients with cancer and diabetes, 44 ( 69,8%) participants suffered from diabetes before cancer diagnosis (p=0,7); 19 ( 30,1%) participants were diagnosed as diabetic patients at diagnosis of cancer (p=0,3). We have found following neoplasia types among diabetes group: 13 patients (1,47%) with diabetes among group of 885 patients (64,9% ) with breast cancer (p=0,01),12 patients ( 3,6%) with diabetes in group of 332 patients (24,3% ) with colorectal cancer (p=0,04). Correlation between other cancers and diabetes was not significant (melanoma, lung cancer, brain tumor, prostate cancer, gastric cancer, pharyngeal cancer, oropharyngeal cancer, lymphoma, pancreatic cancer, bladder cancer , laryngeal cancer, thyroid cancer, testis cancer). Conclusion: 1.Diabetes is linked with some types of cancer. 2. There is a correlation between diabetes and breast and colorectal cancer.
EFFECTS OF A NOVEL BRADYKININ B1 RECEPTOR ANTAGONIST AND ANGIOTENSIN II RECEPTOR BLOCKADE ON AN EXPERIMENTAL MODEL OF MYOCARDIAL INFARCTION IN RATS
1,2 , X. Lin 1 , C. Bernloehr 3 , T. Hildebrandt 3 , H. Doods 3
Department of Research, Mount Sinai Medical Center, Florida, United States of America; 2 Department of BIN Fusion Technology, Chonbuk National University, Korea; 3 Boehringer Ingelheim Pharma GmbH and Co.KG, Biberach, Germany
Objective: The aim of this present study was to evaluate the cardiovascular effects of a novel bradykinin B1 receptor (B1R) antagonist, BI-113823 after myocardial infarction (MI); and to determine whether B1R blockade affects the cardiovascular effects of angiotensin II type 1 (AT-1) receptor antagonist after MI in rats. Methods: Sprague Dawley rats underwent left coronary artery occlusion and randomly assigned to receive treatment of vehicle, B1R antagonist (BI-113823), AT-1 antagonist (irbesartan), and combined treatment of BI-113823 and irbesartan. Seven days after induction of MI, the cardiac function was determined by measuring hemodynamics through left ventricular catheter and by echocardiography analysis. Myocardial B1R, B2R, AT-1, and ACE-1 mRNA expressions were analyzed by RNase-protection assays. Matrix metalloproteinases (MMP)-2 and collagen III expression were measured by western blot analysis. Results: Treatment with B1R and AT-1 antagonist alone and combined treatment of both improved post-MI cardiac function as evidenced by attenuation of the post-MI elevation of left ventricular end diastolic pressure (LVEDP), improved first derivative of left ventricular pressure (± dp/dt max), and improved left ventricle ejection fraction, fractional shorting, and wall motion, as well as attenuation of post-MI up-regulation of MMP-2 and collagen III. In addition, treatment with BI 113823 markedly attenuated the up-regulation of B1R and AT-1, while had minimal effect on B2R and ACE-1 mRNA expression. Conclusion: the present study shows that treatment with novel B1R antagonist, BI-113823 improves post-MI cardiac function, and that B1R blockade with BI-113823 does not affect the cardiovascular effects of AT1 receptor antagonist following myocardial infarction.
PRE-EXISTING DIABETES MELLITUS IS INCREASING THE RISK OF GASTRIC CANCER: A META-ANALYSIS
1 , K.Y. Son 2 , C.S. Eom 3,4 , D. Durrance 5 , S.M. Park 1
Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Korea; 2 Center for Health Promotion, Seoul National University Hospital, Korea; 3 Department of Family Medicine, Hallym University, Chuncheon Sacred Heart Hospital, Korea; 4 Family Medicine, Graduate School of Korea University College of Medicine, Korea; 5 Department of Health Policy and Management, Graduate School of Public Health, Seoul National University, Seoul, Korea
Background: While the association between diabetes mellitus and a variety of cancers is well established, previous meta-analyses have demonstrated inconsistent associations between preexisting diabetes mellitus and subsequent gastric cancer incidence. Supplementing the methodological weaknesses of previous meta-analyses, we performed a meta-analysis to systematically assess the association between diabetes and gastric cancer incidence. Methods: We searched Medline (PubMed), EMBASE, and the Cochrane Library (through Feb 7, 2012), including references of qualifying articles. Case-control studies and cohort studies comparing the risk of gastric cancer between diabetic patients and controls were included. Seventeen studies met our criteria, and we performed a meta-analysis of pre-existing diabetes and gastric cancer incidence. Results: A random-effects model meta-analysis showed an increased gastric cancer risk in diabetic patients (RR=1.19; 95% confidence interval [CI], 1.08 - 1.31). In subgroup analyses, this result persisted in cohort studies (RR=1.20; 95% CI, 1.08 - 1.34), in studies of both western (RR=1.18; 95% CI, 1.03-1.36) and eastern countries (RR=1.19; 95% CI, 1.02-1.38), in female subgroup (RR=1.24; 95% CI, 1.01 - 1.52), and in highly qualified studies (RR=1.17; 95% CI, 1.05 - 1.31). Moreover, these results persisted when analysis was confined to studies adjusted for well-known gastric cancer risk factors such as smoking (RR=1.17; 95% CI, 1.01 - 1.34) or Helicobacter pylori (RR=2.35; 95% CI, 1.24 – 4.46). Interpretations: Preexisting diabetes mellitus may increase the risk of gastric cancer by approximately 19%. While the additional risk is significant in women, it seems to be unrelated to geographical region. Further prospective studies adjusting additional confounders such as diabetes interventions are needed to specifically test the effect of diabetes mellitus on gastric cancer risk.
INCIDENCE OF SOME VIRAL INFECTIONS AMONG DIABETIC PEOPLES IN NAJAF, IRAQ
1 , A.M.S. Baqer 2 , N.A. Abdulkhedir 3 , H.M. Al-alaq 4
Al-Qadiysia University, College of Science, Biology Department, Dewania, Iraq; 2 Kufa University, College of Medicine, Kufa, Iraq
During the last ten years the incidence of diabetes (both type I & type II) was increased markedly in Iraq and many studies had been performed to reach the possible underlying causes. In this study we enrolled patients with diabetes (type I & type II) from different age groups and blood was collected from each of them for viral screening (by ELIZA and PCR methods) including enterovirus, cytomegalovirus, rubella, mumps &hepatitis viruses (A,B&C). Our results shows among 112 diabetic patients 55 patients had different viral infections, most patients with type I diabetes had enterovirus & cytomegalovirus (52% (13/25) & 32% (8/25) respectively), while patient with type II diabetes had more infected with hepatitis C&B (66% (10/30) & 20% (6/30) respectively). We conclude that viral infections may play an etiological role in causation of both types of diabetes at different age groups in Iraq.
SREBP1 TARGETED GENE EXPRESSION PROFILE IN NEONATAL MICE LIVER WAS CHANGED BY MATERNAL DIET DURING GESTATION: MICROARRAY AND BIO-ANALYTIC BASED RESEARCH
Capital Medical University, Beijing, China
Maternal diet has long been recognized as a significant factor effects on offspring‟ development and health. But the target genes affected by maternal high lipid diet were unknown. In this study, neonatal mice liver‟ gene expression profile was analyzed by chips to find genes which expressions were significantly changed by maternal diet during gestation. Real time PCR and western blot were used to measure some key genes found by microarray. Serum lipids, glucose and insulin levels of adult offspring from dams fed with chow or high lipid diet were measured using commercial kits. The results indicated that the expression of genes involved in cholesterol and fatty acids synthesized were significantly inhibited while the expressions of genes involved in glycolysis were decreased significantly by maternal diet during gestation. Bio-analytic results showed that SREBP1 might be the key gene which regulates the genes involved in fatty acids, glucose and cholesterol metabolizing.
EFFECT OF HIGH-FAT DIET AND MYRIOCIN ON THE LEVEL OF SELECTED SPHINGOLIPIDS IN THE RAT LIVER
M. Żndzian-Piotrowska, D.M. Piotrowska, K. Kurek, P. Wiesiołk, J. Górski
Department of Physiology, Medical University of Białstok, Białstok, Poland
Certain sphingolipids play very important role in many physiological and pathological processes. Ceramide (CER), a key compound in sphingolipid metabolism is generated from sphingomyelin and synthetized de novo from serine and palmitoyl-CoA. Serine palmitoylotransferase (SPT) is the first enzyme engaged in ceramide de novo synthesis. The aim of the study was to examine the effect of high-fat diet and myriocin (SPT inhibitor) on the level of selected sphongolipids in the rat liver. The experiment was carried out on male Wistar rats. The animals were divided into four groups: 1) control group, fed with standard rodent diet, 2) group, fed with high fat diet for 3 weeks, group, 3) group fed with standard diet and treated with myriocin for 7 days, 4) group fed with high fat diet and treated with myriocin. The animals were sacrificed and the samples of the liver and blood were taken. The liver samples were frozen in liquid nitrogen. Sphingomyelin (SM) was isolated by means of thin layer chromatography. CER, sphingosine (SFO) and sphingosine-1-phosphatate (S1P) were quantified by means of high performance liquid chromatography. It has been found that SM and CER were also elevated in high fat diet group. Compared with control group, myriocin reduced total content of SM, CER, SFO, S-1-P in the rat liver. Moreover, high fat diet animals treated with myriocin had levels of SM and CER markedly decreased, similar with control groups. It can be concluded that treating with myriocin changes sphingolipid metabolism in the rat liver.
ASSOCIATION STUDY BETWEEN TAQ-SNPS AND HAPLOTYPES OF CELL DEATH-INDUCING DNA FRAGMENTATION FACTOR ALPHA-LIKE FACTOR A (CIDEA) GENE AND OBESITY IN CHINESE HAN POPULATION
1,2 , J. Wu 1,2 , J. Zhang 1,2 , Y. Dai 1,2 , L. Bian 1,2 , W. Wang 1,2,3,4
Department of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Capital Medical University, Beijing, China; 2 Municipal Key Laboratory of Clinical Epidemiology, Beijing, China; 3 College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing, China; 4 Edith Cowan University, Perth, Australia
Objective: To assess the association between the taq-SNPs and the haplotype structures of CIDEA gene and obesity. Material and Methods: Six taq-SNPs (including V115F) were genotyped in a case-control study. Blood samples and anthropometric measurements of subjects were collected. SPSS 19.0, Haploview 4.0 and Multifactor Dimensionality Reduction (MDR) software were used for statistical analysis. Results: CIDEA gene V115F polymorphism is identified to be a risk biomarker in Chinese, TT genotype was associated with an increase susceptibility of obesity compared with GG group(P=0.017, OR=2.558, 95%CI: 1.180-5.546). Two other new SNPs and two haplotypes were found to be associated with obesity in Chinese. Subjects with SNP1-GG and SNP2-CC had higher levels of waist circulation, and were seem to be associated with higher susceptibility to obesity (OR=2.186, 95%CI: 1.091-4.378, P=0.027; OR=4.367; 95%CI: 1.208-15.796, P=0.003) adjusted for age and gender. There were much higher frequency of haplotype GTTTC in obese patients (35.13%, OR=1.465, 95%CI: 1.053-2.038, P=0.023), while lower frequency of haplotype TTTGC (5.00%, OR=0.489, 95%CI=0.235-1.015, P=0.050) than control group. There was an interactive effect between SNP1 and SNP2 on obesity, subjects with SNP1/GG and SNP2/TT simultaneously seems to be a protective factor of obesity in Chinese Han population (P=0.027, OR=2.146, 95%: 1.092-4.217). Conclusion: V115F/T allele, SNP1/G allele, SNP2/C allele and haplotype GTTTC of the CIDEA gene were risk factors, while haplotype TTTGC of the CIDEA gene were protective factors for obesity in Chinese Han population. The strong interaction between SNP1/SNP2 should be taken more attention in further obesity researches.
OSBP-RELATED PROTEINS (ORPS) IN HUMAN ADIPOSE DEPOTS AND CULTURED ADIPOCYTES: EVIDENCE FOR IMPACTS ON THE ADIPOCYTE PHENOTYPE
1 , M.R. Robciuc 2 , M. Wabitsch 3 , A. Juuti 4 , M. Leivonen 4 , C. Ehnholm 2 , H. Yki-Järvinen 1,5 , V.M. Olkkonen 1,6
Minerva Foundation Institute for Medical Research, Helsinki, Finland; 2 National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki, Finland; 3 Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany; 4 Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland; 5 Department of Medicine, University of Helsinki, Helsinki, Finland; 6 Institute of Biomedicine, Anatomy, University of Helsinki, Finland
Oxysterol-binding protein (OSBP) homologues, ORPs, are implicated in lipid homeostatic control, vesicle transport, and cell signaling. We analyzed here the quantity of ORP mRNAs in human subcutaneous (s.c.) and visceral adipose depots, as well as in the Simpson-Golabi-Behmel syndrome (SGBS) adipocyte cell model. All of the ORP mRNAs were present in the S.c and visceral adipose tissues, and the two depots shared an almost identical ORP mRNA expression pattern. SGBS adipocytes displayed a similar pattern, suggesting that the adipose tissue ORP expression pattern mainly derives from adipocytes. During SGBS cell adipogenic differentiation, ORP2, ORP3, ORP4, ORP7, and ORP8 mRNAs were down-regulated, while ORP11 was induced. To assess the impacts of ORPs on adipocyte differentiation, ORP3 and ORP8, proteins down-regulated during adipogenesis, were overexpressed in differentiating SGBS adipocytes, while ORP11, a protein induced during adipogenesis, was silenced. ORP8 overexpression resulted in reduced expression of the aP2 mRNA, while down-regulation of adiponectin and aP2 was observed in ORP11 silenced cells. Furthermore, ORP8 overexpression or silencing of ORP11 markedly decreased cellular triglyceride storage. These data identify the patterns of ORP expression in human adipose depots and SGBS adipocytes, and provides the first evidence for a functional impact of ORPs on the adipocyte phenotype.
TWO YEARS ASSESSMENT OF VILDAGLIPTIN SAFETY AND EFFICACY IN TYPE 2 DIABETES PATIENTS (T2DM) IN RUSSIAN REAL CLINICAL SETTING
1 , M.V. Shestakova 2
Department of Endocrinology, First Moscow State Medical University, Russia; 2 Russian Endocrine Research Centre, Russia
Aim: to evaluate the efficacy and safety of vildagliptin alone or in combination with metformin and SU in real practice. Study design: Two years observational study of vildagliptin efficacy on glycemic and metabolic control (HbA1c, Fasting Blood Glucose, BMI) in T2DM patients. More than 3500 newly diagnosed or diet treated T2 DM patients were prescribed by vildagliptin 50 mg bid, and then split into 3 groups: vildagliptin monotherapy (n=435), vildagliptin+metformin (n=2348) and vildagliptin+SU (gliclazide, glibenclamide, glimepiride) (n=561). The type of therapy was due to physician choice. Results: The significance improvement of glycemic control has been shown in all groups: HbA1c(%) from baseline 8.2% [7.9–8.6] decreased by -1.5, -1.6, and -1.8, p<0.001, in vildagliptin monotherapy, vildagliptin+metformin and vildagliptin+SU, respectively. FBG (mmol/l) from baseline 8.4 [8.2-9.0] decreased by -2.36, - 2.61, -2.93, p<0.001, respectively. Mean BMI (kg/m2) reduced by -1.12%, -1.65%, and -1.23%, respectively. We performed the Separate analysis for 210 patients older 70 y.o. (mean age 73) by the same groups: vildagliptin monotherapy (N=27), vildagliptin+metformin (N=107) and vildagliptin+SU (N=76). HbA1c decreased from baseline 8.2% [7.7–8.5] by -1.3%, -1.6%, and -1.6% p<0.001, respectively. FBG (mmol/l) from baseline 8.5 [8.11-8.79] decreased by -2.16, -2.47 and -2.54 p<0.001, respectively. BMI (kg/m2) decreased by -0.6%, -1.0%, and -0.7%, respectively. Conclusions: Vildagliptin in different treatment regimens was good tolerated, effective and safe in routine clinical practice. Improvement of glycemic control was significant and long-lasting treatment.