ENERGY RESTRICTED HIGH ANIMAL PROTEIN DIETARY PATTERNS, BLOOD GLUCOSE AND LIPID PROFILES, COGNITIVE AND RENAL FUNCTION IN TYPE 2 DIABETES
K. Pearce^1,2, M. Noakes¹, P. Clifton^1
1)Commonwealth Scientific and Industrial Research Organization (Csiro), Health Sciences and Nutrition, Adelaide, South Australia, Australia 5000 ²⁾Department Of Physiology, University of Adelaide, Adelaide, South Australia, Australia 5000

Objective: To investigate the effect of hypocaloric high (animal) protein diets either low (Lchol) or high in dietary cholesterol (from eggs; Hchol) on plasma lipids, glycemic control, cardiovascular risk markers, cognitive and renal function in Type 2 diabetes. We hypothesized that dietary cholesterol would have no effect on low density lipoprotein cholesterol (LDL-C) and all other parameters would improve. Methods: 82 participants with type 2 diabetes (age; 54.4+8.2, BMI; 34.1+4.8 kg/m2, microalbuminuria; 9.6+3.9mg/24hr, LDL-C; 2.67+0.10mmol/L)) were randomised to either Hchol or Lchol for 12 weeks. Both 6MJ dietary interventions contained a total carbohydrate: protein: fat ratio of 40%:30%:30%, but differed in cholesterol content; (Hchol; 590mg cholesterol, Lchol; 213mg cholesterol). A cognitive battery of tests was used at 8 weeks .Results: Overall, weight loss was 6.0+0.4kg (p<0.001). LDL-C, homocysteine, microalbuminuria(mg/24hrs) and cognitive function remained unchanged (p=0.899, p=0.369, p=0.490, p>0.05 respectively). There was a significant effect of time on total cholesterol (-0.3+0.1mmol/L; p<0.001), triacylglycerol (-0.4+0.1mmol/L; p<0.001), non high density lipoprotein cholesterol (-0.4+0.1mmol/L; p<0.001), apolipoprotein-B (-0.04+0.02gl/L; p=0.003), HbA1c (-0.6+0.1%; p<0.001), fasting blood glucose (-0.5+0.2mmol/L; p=0.005), fasting insulin (-1.7+0.7mU/L; p=0.003), systolic blood pressure (-7.6+1.7; p<0.001) and diastolic blood pressure (-4.6+1.0mmHg; p<0.001) independent of diet, gender, medication or weight loss. There was a diet x time interaction for high density lipoprotein cholesterol (HDL-C) which increased on Hchol (+0.02+0.02mmol/L) and decreased on Lchol (-0.07+0.03mmol/L; p=0.014(. Conclusion: Both high protein energy restricted diets improved glycemic and lipid profiles, blood pressure and apolipoprotein-B in individuals with type 2 diabetes. The HDL-C response to Hchol was greater than Lchol.


SERUM TYPE IV COLLAGEN AND ANTI-TYPE IV COLLAGEN ANTIBODIES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND DIFFERENT DURATION OF THE DISEASE
M. Pektova

Results: Mean age of the patients with Type 2 DM and control subjects was not statistically different. The level of HbA1c was statistically significant higher in patients with newly-diagnosed Type 2 DM compared to the patients with 3-years duration of the disease (11.5±0.6 vs.8.08±1.62%; p<0.005). The level of collagen IV in patients with microalbuminuria (MA) in both groups of diabetic patients was significantly lower compared to this in patients without MA (p<0.001) and controls (ð<0.05). Anti-collagen IV IgM antibodies in patients with 3 years-duration of Type 2 DM and MA were statistically significant higher compared to the patients in the same group without MA (p<0.05). The levels of anti-collagen IV IgM antibodies in patients without MA were statistically significant higher in group with newly-diagnosed diabetes compared to the group with 3 years-duration of the disease. There were not any differences between the levels of ACAB in diabetic patients and control subjects. In patients with 3 years-duration of diabetes and MA we found statistically significant (p<0.0001) correlation between the levels of collagen IV and HbA1c (r=0.99). Collagen IV concentrations showed significant correlation ( p<0.002) with blood pressure (r= -0.96) in patients with MA from both groups. Conclusion: The lower levels of serum type IV collagen in our patients with MA compared to the patients without MA, suggested a functional impairment in basement membranes in this stage of diabetic nephropathy. Serum collagen IV level may be used as an indicator of early renal dysfunction in diabetes.


OBESE WOMEN WITH POLYCYSTIC OVARY SYNDROME AND INSULIN RESISTANCE PRESENT HIGHER LEVELS OF VISCERAL FAT
F. Penaforte, C. C Japur, R. Wd Garcia, M. Nc Vieira, P. G Chiarello
Faculdade De Medicina De Ribeirio Preto Da Universidade De Sao Paulo, Ribeirio Preto, Brasil.

Introduction: The Polycystic Ovary Syndrome (PCOS) is associated with aspects of metabolic syndrome, such as abdominal obesity and insulin resistance (IR). Objectives: To assess body composition of obese patients with PCOS with and without IR. Methodology: obese patients with PCOS were evaluated and separated into groups with and without IR. The IR was characterized by a QUICKI index less than 0.34. Variables analyzed were weight, age, waist circumference, total fat mass and arm fat by segmental bioelectrical impedance; trunk fat and total, visceral and subcutaneous abdominal fat by computed tomography. Statistical analysis were performed by Mann-Whitney test (p <0.05). Results: Groups were 20 patients with IR and 11 without IR. There is no difference in age (years), weight (Kg), total fat mass (Kg) or subcutaneous abdominal fat mass (g) between groups. But, women with PCOS and RI had more trunk fat mass (374.0 ± 78.1g x 282.4 ± 83.4g, p < 0,05), total abdominal fat mass (460.7 ± 83.7g x 391.8 ± 88.2g, p < 0,05) and visceral abdominal fat mass ( 78.4 ± 23.5g x 60.2 ± 20.3g, p < 0,05) and less arm fat mass (16.0 ± 2.6Kg x 18.1 ± 6.3Kg, p < 0,05) than women without RI. Conclusion: Women with PCOS and IR had greater trunk fat and total and visceral abdominal fat, while those without IR, had higher arm fat, more characteristic of subcutaneous body fat.


GENDER, AGE AND GENETIC FACTORS AS RISK PREDICTORS FOR ATHEROSCLEROSIS AND ITS COMPLICATIONS
V. Perovic
Institute for Cardiovascular Desease "Dedinje", Belgrade, Milana Tepica 1, Serbia

Atherosclerosis is the process that develops in the arteries of practically all humans.The frequency and severity of atherosclerosis as well as the incidence and mortality of its complications increase considerably in all populations investigated.There is a universal excess of incidence,mortality and coronary atherosclerosis associated with the male sex,declining with age but persisting well beyond menopause.Various studies have showed familiar aggregation of coronary heart disease (CHD) and support overall significant independent association of family history of CHD,mainly developed at an early stage of life,with the risk of CHD.Poligenic factors as well as association with enviromental factors may be directly involved with “classical” risk factors.It is certain that identification of both genetic and environmental factors will provide major answers needed for the understandging and prevention of the atherosclerosis process,especially among susceptible subpopulation with a positive family history of the disease.


AMAZONIC FISHES IMPROVE THE CARDIOVASCULAR PROTECTION THROUGH HDL-CHOLESTEROL INCREASE AND DECREASING OF VLDL-CHOLESTEROL AND TIACYLGLYCEROLS
R. Piccolotto Carvalho¹, F. Souza², J. Monteiro¹, C. Nascimento³, L. Oyama³, N. Garcia¹, D. Coelho¹, C. In ácio¹, R. Sales^1
1)Departamento De Ciencias Fisiológicas (Dcf), Instituto De Ciencias Biologicas (Icb), Universidade Federal Do Amazonas (Ufam), Manaus, Am, Brasil ²⁾Programa De Pós-Graduaço Em Biotecnologia, Centro De Apoio Multidisciplinar (Cam),Ufam. Manaus, Am, Brasil. ³⁾Departamento De Neurofisiologia E Nutriço, Universidade Federal De Sao Paulo (Unifesp), Sao Paulo, Sp, Brasil.

The obesity as a multifatorial disease has various genetics aspects in its physiopathogeny. It’s known that diets riches in greasy acids also favors the disease besides, the leptne is on important part of the metabolism and of the obesity. Studies done about it show the modification in the lipidic metabolism by the intake of diets based on amazonic fishes, rich in polyunsaturated greasy acids. So these studies intend to evaluate hormonal-biochemistry alterations in rats that went under such diet. Forty male Wistar rats (Rattus novergicus) thirty days old, were divided in four grops (n=10) fed ad libitum for thirty days with: “mapar” Hypophthalmus edentatus (Gmap), “matrinx” Brycon amazonicus (Gmat) and “tambaqui” Colossoma macropomum (Gtam) and regular fodder (GC). After wards one four ml sample of blood was taken from the heart. They were analyzed in series to check glucose, Triacylglycerols, total Cholesterol, HDL-Cholesterol, VLDL-Cholesterol, LDL-Cholesterol, Leptin and Insulin. There was a significant reduction in Gtam Glycemy compared to the others, significant reduction in the Triacylglycerols and VLDL-Cholesterol of Gmap, Gmat and Gtam compared to the GC. Insulin levels weren’t different significantly among the groups. It was observed a significant fall of total Colesterol in Gmat and Gtam. The HDL-Cholesterol increased significantly in Gmap and Gtam. The LDL-Cholesterol levels increased significantly only in Gmap. It had increased of leptin in the groups is compared to GC. However, the present study showed that amazonic fishes, principally “tambaqui” can cause hormonal-biochemistry changes, causing the increasing of HDL-Cholesterol in the organism, that mean an important vehicle of cardiovascular protection.


THE INFLUENCE OF MEDICAL NUTRITIVE THERAPY ON MAJOR RISK FACTORS FOR TYPE 2 DIABETES IN OBESE PEOPLE
S. Polovina¹, K. Milenkovic², M. Novkovic^3
1)General Hospital Subotica, Serbia ²⁾General Hospital Cacak, Serbia ³⁾General Hospital Vrbas, Serbia

Introduction: The major risk factors for diabetes type 2 in obese people are body mass index, waist circumference, glucose toleration, insulin resistance, hypertension, increased serum lipids. Material and methods: We have analyzed the changes in some of risk factors for diabetes type 2 in obese people after 6 months on low calorie (1200-1500kcal/day), high fibers diet (20-40g/day), with 55-65% carbohydrates, 15-18% proteins and 22-23% fats (predominantly unsaturated fats). 75 subjects were divided in two groups. Examined group (N=50) treated with recommended diet and control group (N=25) treated with standard low calorie diet (CH 35-45%, dietary fibers 10-15g/day, proteins 20-25% and fats 20-30%). Findings: After six months fasting glucose was significantly decreased (p<001) in examined group, and NS in control group (p=0.8). BMI was decreased in examined group (p<0.001) more than in control group (p=0.28). Waist circumference decrease significantly (p<0.001) in examined, but not significantly (p=0.17) in control group. Insulin resistance was calculated by HOMA IR and there was significantly lowering values in examined group (p<0.001) than in control group ( p=0.05). Insulin sensitivity calculated by HOMA had no statistic significantly changes. Triglycerides and systolic blood pressure decreased in examined group (p=0.001) but control group had more significant decrease of diastolic bloods pressure. Diabetes type 2 was appeared in 2 subjects (5.7%) in control group and no one in examined group after 6 months. Conclusion: These results suggests that low calorie high fiber diet had positive effect on most potent risk factors for type 2 diabetes like fasting glucose, insulin resistance, waist circumference and body mass index.


CARDIOVASCULAR TESTS IMPORTANCE IN DIAGNOSTIC OF DIABETIC CARDIOVASCULAR AUTONOMIC NEUROPATHY
S. Popovic-Pejicic¹, D. Rodic², G. Malesevic¹, S. Dunovic^3
1)Clinical Center of Banja Luka, Clinic for Endocrinology, Diabetes and Metabolic Diseases ²⁾Clinical Center of Banja Luka, Clinic for Cardiovascular Diseases ³⁾Medical Faculty, University of Banja Luka, Bosnia and Herzegovina

Diabetic cardiovascular autonomic neuropathy (DCAN) is chronic complication of diabetes mellitus, frequently without any symptoms, and with high mortality, that’s why it demands early detection. Aim of this work was to establish: possibility of DCAN early detection with cardiovascular dynamic tests; diagnostic value each of those cardiovascular tests. During this work we have evaluated 90 examinees: 30 of them with diabetes type 1, 30 with diabetes type 2 and 30 healthy examinees – without primary cardiac disease and diabetes. Autonomic nervous system function was examined with 5 tests for cardiovascular reflexes. Results have showed that the most common pathological test in diabetes type 1 (71,4%,p<0.001) and type 2 (83,3%,p>0.001) was stand-up from lying position test, and afterwards deep breathing test – in diabetes type 1 (66,7%,p<0.001) and type 2 (80,0%,p<0.001). Valsalve maneuver, orthostatic hypotension test and Hand grip test was pathological in 33,3% of the patients with autonomic neuropathy in type 1 of diabetes, in type 2 (46,7%,13,3% and 20,0%).Cardiovascular tests are enabling us DCAN early detection and objective cardiovascular evaluation, and from that reason are having great prognostic, diagnostic and therapeutic value. Stand-up from lying position test and deep breathing test were the most often pathological in DCAN patients, considering that, they have the greatest diagnostic importance. Cardiovascular tests should be accepted as gold standard in DCAN diagnostic and imported in everyday clinical practice. Right interpretations of these tests are enabling categorization of damage degree in autonomic nervous system, which has great importance in further treatment and management of these patients.


DIABETIC AUTONOMIC NEUROPATHY – PREDISPOSE MICROVASCULAR COMPLICATIONS IN DIABETIC TYPE 2
S. Popovic-Pejicic¹, D. Rodic², D. Beric¹, B. Radosevic¹, V. Soldat¹, G. Malesevic^1
1)Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Banja Luka ²⁾Clinic for Cardiovascular Diseases, Clinical Center Banja Luka

Diabetic autonomic Neuropathy (DAN) is an important chronic complication of Diabetes that affect many physiological systems and is associated with a significant deterioration in the quality of life and increased morbidity and mortality. The aim of study was to determine both presence and extent of DAN, in diabetic type 1 and type 2 (insulin dependent); correlation DAN with degree of metabolic control of diabetes; its correlation with other microvascular complications of diabetes (retinopathy, nephropathy and peripheral neuropathy). We have examined 90 subjects classified into three groups with 30 patients each: those with type 1 diabetes, type 2 diabetes insulin dependent and control group of healthy subjects. All patients underwent cardivascular tests (Valsalva maneuver, deepbreathing test, response to standing, blood pressure response to standing, sustained handgrip test). For estimation of microvascular complications were done ophtalmologic exam, electromioneurography test and determine proteinuria in 24h in urine. The degree of metabolic control of diabetes was estimated according to preprandial and postprandial blood glucose and HbA1 levels. Our results have shown DAN to occur more frequently in type 2 diabetes (in insulin dependent patients) (p<0.001) and as a manifesting DAN (60%,p<0.001). The presence of DAN did not necessarily be only the consequence, but most probably the predcessor of hyperglycemia. In insulin dependent type 2 diabetes patients associated with DAN, occurence of retinopathy and nephropathy is more frequent (66.7%,p<0.01), so as peripheral neuropathy (90%,p<0.01). The presence of DAN in insulin dependent patients with type 2 diabetes is a predprocessor for development of diabetic micro-vascular complications.


THE PREDICA STUDY (PREDICTION OF DIABETES FROM CAPILLARY BLOOD GLUCOSE) IN THE GENERAL POPULATION
P. Pozzilli¹, A. Picardo¹, F. Costanza¹, E. Di Stasio², N. Napoli¹, F. Carrano³, V. Dell'Anna³, W. Macino^3
1)University Campus Bio-Medico, Rome, Italy ²⁾Catholic University, Rome, Italy ³⁾Federazione Medici Di Medicina Generale, Rome & Frosinone, Italy

Diabetes raises clinical and social concerns due to its chronic complications and its prevention should be implemented in the general population. In Italy prevalence of type 2 diabetes (T2D) is 4.5% whereas scarce data is available on the number of subjects with abnormal glucose metabolism. The aim of this study was to detect abnormalities in glucose metabolism in a non diabetic adult population attending offices of general practitioners (GPs). Primary end points were the assessments of subjects compliance with home capillary blood glucose measurement and the identification of those with impaired fasting glucose (IFG), impaired glucose tolerance IGT or latent diabetes. 50 GPs, in Rome and Frosinone, consecutively enrolled 538 non diabetic subjects (175 M, 225 F, mean age 55±9 yrs). Subjects were instructed to perform 8 fasting and 8 two-hour post-meal glucose determinations over a period of 2 months. Overall 90% of the study population performed at least 5 glucose determinations in the 2 months period (58% completed 13 to 16 glucose determinations; 68% 5 to 8 fasting and 2 hours post-meal measurements). Alterations in blood glucose were detected as follows: 22% of subjects were classified as IFG (>110 mg/dl) and 12% showed abnormal post-prandial glucose (>140 mg/dl), 14% showed at least one value of abnormal fasting or post-prandial glucose. Finally, 36 subjects (6%) were diagnosed with T2D. The use of a glucometer among the general population can represent an easy tool in the detection of blood glucose metabolism alterations or early diagnosis of diabetes.


PREVALENCE OF THE METABOLIC SYNDROME AMONG PATIENTS WITH TYPE 2 DIABETES IN NORH-CENTRAL NIGERIA
F. Puepet^1,2, A. Uloko², S. Kabir², I. Akogu^2
1)Jos University Teaching Hospital ²⁾Diabetes Screening and Care Foundation,Nigeria

Background: In most people with glucose intolerance or type 2 DM, there is a multiple set of risk factors that commonly appear together forming what is now known as the ‘Metabolic Syndrome’. This ‘clustering’ of metabolic abnormalities that occur in the same individual appear to confer substantial additional cardiovascular risk. There is a paucity of reports on the Metabolic syndrome among Nigerians. Objective: The objective of this study was to determine the prevalence of the Metabolic Syndrome among North-Central Nigerians with type 2 diabetes and to describe the frequency of the syndrome’s components. Methods: Six hundred and twenty four (624) patients with type 2 diabetes attending the out-patient clinic of the Diabetes Screening and Care Centre, Jos, Nigeria were screened for the metabolic syndrome. A brief history was obtained and their anthropometric indices and blood pressure were measured. Fasting venous plasma samples were analysed for lipids. The diagnosis of Metabolic Syndrome was made based on the new IDF definition. Results: Of the 624 patients enrolled with mean age 54(13) years, 56% were females. The prevalence of Metabolic Syndrome was 76% (82% females, 68% males). The mean age of Patients with Metabolic Syndrome was 58(13) years. About 80% of the patients were centrally obese 76% had hypertension, 62% had high triglycerides and 70% with low HDL-Chol. Conclusion: The prevalence of the Metabolic Syndrome in this group of upland Nigerian patients with type 2 diabetes is high . This probably reflects the adoption of Western lifestyles that require urgent intervention.


FATTY LIVER IN OVERWEIGHT AND OBESE PATIENTS IN WESTERN PART OF SAUDI ARABIA
F. Qari
King Abdul Aiziz Hospital, Saudi Arabia

Objective: The aim of the study is to determine the association of fatty liver diagnosed by ultrasound and obesity in patients presented to King Abdul aziz university hospital. Methods: A clinical notes review was performed of all patients undergoing evaluation for fatty liver associated with obesity over one year period. Data included age, gender, nationality, BMI, serum level (ALT) (AST), HbA1C , cholesterol, triglyceride, LDL, and TSH, and clinical presentation of abdominal pain or the presence of hepatomegaly. Results: A total of 235 subjects were enrolled in the study .The mean age of the study group was 46 +/-14.4 years with 82 males (35 %) and 153 females (65%). Mean +/- SD AST level was 43.9+/6.18.1units /L, ALT was 36.2+/-5.1 units /L. Values of transaminase above the normal range was present in 15 (6.4%) patients only. Whereas values of cholesterol and triglyceride above normal range was seen in (7.2%) 17 patients. Over weight and obesity were the main risk factors in our study group. Mean BMI was 33.6 +/- 7.5 Kg/m2. Obesity with diabetes is the most important risk for fatty liver. 78 (33 %) of our study group patient were diabetic. Conclusion: Overweigh and obesity is the most important risk factor for fatty liver in Saudi Arabia. It is more prevalent in females. . Ultrasound appears to be a useful non-invasive tool to determine liver involvement with fatty liver in obese adult even in the absence of hypertraninasemia.


GLYCEMIC AND GOOD TARGET CONTROL AMONG DIABETICS AT A UNIVERSITY AND ERFAN PRIVATE HOSPITAL
F. Qari
King Abdul Aiziz Hospital , Saudi Arabia

Objective: To determine and compare a good target level of blood sugar control assessed by HBAIc , blood pressure and serum LDL – cholesterol in diabetic patients attending out-patients clinics at King abdul Aziz university , government hospital and patients attending out-patients clinics at Erfan and Bageddo private hospital in Jeddah in Saudi Arabia. Methods: - This is a cross section study conducted at two month period between January 2005 and February 2005 in two centers (KAUH) and Erfan Bageddo hospital. Results: 200 patients, 100 from each hospital were enrolled in the study. Females accounted for 70% at KAUH group versus 54 % in Erfan group. Saudi patients attending Erfan group were 62 % compared to 51 % in KAUH group. Mean HbAIc was almost the same in both groups 7.8+/-1.8 mmol/L. good and acceptable HBAIc was observed in 58 % at KAUH group versus 54 % at Erfan group. The blood pressure target control was good in both groups; however target LDL- cholesterol was scientifically better in Erfan group 1.88+/-1.2 versus 3.22+/.9 m mol/ L in KAUH group with significant p value of 0.0001. The low rate of aspirin use amongst diabetic patients was observed more in KAUH study group compared to Erfan group In conclusions: Even after great efforts, a target level of HBAIc glycated hemoglobin not achieved in both groups of patients – in private and governmental hospitals. LDL- cholesterol was not achieved n governmental hospital.


BACTEREMIA AND SEPTICEMIA IN DIABETIC PATIENT IN WESTERN REGION OF SAUDI ARABIA
F. Qari
King Abdul Aiziz Hospital , Saudi Arabia

Objective:The present study aims to define the pattern of bacteremia with clinical sepsis in diabetic patients at King Abdul aziz university hospital in relation to the type of infection, microbial pattern , source, complication, outcome, and the risk factors associated with high mortality. Methods: Retrospective study of adult diabetic patients with bacteremia and septicemia admitted to King Abdul Aziz university hospital during the two years period Results: Total of 4850 blood culture were submitted to the microbiology lab of KAUH over two years period. 290 (6%) cases had positive blood cultures , 70 were diabetic patients with incidence rate of 24 % with p value of 0.043 which is statically significant. Urinary tract infection was the most common source of bactermia in our study group with E coli as the commonest organism in 62 %. Mortality rate was 44 %. Old age was an important risk factors for high mortality with p value 0.011value, which is statically significant. Other risk factors included cormobidity associated with diabetes, septic shock, mechanical ventilation and DIC. Conclusion:Increase age was one of the important risk factors for high mortality rate in our study group. Good empiric antibiotics coverage should be instituted early in high risk groups .


DISCOVERY OF GRC 9332 A NOVEL STEAROYL COA DESATURASE ENZYME1 (SCD1) INHIBITOR, THAT MODULATES PLASMA LIPIDS WITHOUT INDUCING OCULAR OR CUTANEOUS LESIONS
S. Rao, V. Bhosale, D. Wale, V. Baragi
Glenmark Pharmacueticals Ltd, Mumbai, India

Introduction: Hyperlipidemia confers increased risk of atherosclerosis. In order to significantly reduce the burden of this cardiovascular disease, lipid-lowering therapy such as statins is recommended for dyslipidemia. However, recent findings on Stearoyl CoA desaturase enzyme1 (SCD1) as the rate limiting enzyme in the biosynthesis of triglycerides (TG) and cholesterol esters has led to pursuit of this enzyme as a target for obesity and dyslipidemia. Development of SCD1 inhibitors, however, has been hampered by the development of ocular and cutaneous lesions. This study reports on the discovery of a SCD1 inhibitor, GRC 9332, that demonstrated reduction in plasma TG and cholesterol without inducing ocular or cutaneous lesions in a chronic mouse model of poloxamer-induced dyslipidemia. Methods: Poloxamer (P-407) was injected intraperitonially @ 0.5g/kg every third day to a group of C57BL6/J mice for a period of 175 days to induce dyslipidemia. GRC 9332 was administered orally (b.i.d) to mice at doses of 10, 3 and 0.3 mg/kg. Atorvostatin was administered at 20mg/kg (b.i.d) as a positive control. Results: Chronic injections of poloxamer in the vehicle treated groups resulted in an 8.2, 10.7 and 61-fold increase in plasma levels of cholesterol, LDL and TG respectively, compared to saline control (Figs 1-3). Treatment with 10mg /kg GRC 9332 showed a significant (p<0.001) decrease in plasma cholesterol, triglycerides and LDL levels. No ocular or skin pathology was observed even after 38 days of treatment with GRC 9332. Conclusion: GRC 9332 was safe and efficacious in the poloxamer-induced chronic model of dyslipidemia.


HIGH WAIST CIRCUMFERENCE AS A MARKER OF CARDIOMETABOLIC RISK FACTORS: THE 5A STUDY
I. Raz¹, C. Aguilar-Salinas², A. Avezum³, E. Bruckert⁴, J. Chan⁵, A. Misra⁶, A. Sharma⁷, T. Van Der Merwe^8
1)Hadassah University Hospital, Jerusalem, Israel
²⁾Col Tlalpan, Mexico City, Mexico ³⁾Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil ⁴⁾Pitié Salpétrière Hospital, Paris, France ⁵⁾The Chinese University of Hong-Kong, Hong-Kong ⁶⁾Fortis Group of Hospital, New Delhi, India ⁷⁾Royal Alexandra Hospital, Edmonton, Canada ⁸⁾Unitas Hospital, Pretoria, South Africa

Aims: In most countries, there are limited data to define abdominal adiposity and associated clinical profiles. The 5A Study in subjects with a high waist circumference (WC) (¡Ã90 cm for men and ¡Ã80 cm for women) examined the prevalence of cardiometabolic risk factors (CMRF), defined as type 2 diabetes (T2D), dyslipidemia (DL), hypertension (HT) and cardiovascular diseases (CVD), as a function of WC. Methods: This cross-sectional study of 6291 individuals was carried out in eight countries by randomly selected physicians. The number of CMRF was clustered into 5 WC classes both in men and women. Distribution of patterns of CMRF clustering was compared amongst the WC classes using Chi©÷ test. Results: There was a stepwise increase in CMRF clustering with increasing WC, with 3 or 4 CMRF in 47.6% of men with a WC >130 cm and 34.6% of women with a WC >120 cm. Corresponding proportions were 31.6% of men with a WC=[90-100[ cm and 13.1% of women with a WC=[80-90[ cm. The prevalence of T2D or HT was higher in both men and women with the highest WC, whereas the prevalence of DL or CVD was higher in women with the highest WC, but not in corresponding men. Conclusion: In this population with high WC, there was stepwise increase in CMRF clustering with increasing WC. This was less pronounced in men who had high prevalence of CMRF even in the lowest WC class, suggesting that a lower WC cutoff value is needed to identify these high-risk subjects.

PREVALENCE OF DIABETES AND OBESITY AMONG MALAYS IN RURAL AND URBAN MALAYSIA
R. Razali, F. Abd Majid, T. Tengku Ismail,
A. Krishnapillai, N. Mat Nasir, A. Ramli, N. Mohd Noor Khan, H. Mohd Nawawi, K. Yusoff
Faculty of Medicine, Universiti Teknologi Mara, Shah Alam, Selangor, Malaysia

Introduction : Coronary heart disease (CHD) continues to be a leading cause of death around the globe. Diabetes and obesity are the important risk factors for CHD. Objective: To investigate the status of diabetes and obesity among Malays in rural and urban areas in Malaysia. Methods: Cross-sectional community-based study were conducted in urban and rural populations in Malaysia. 3113 subjects (1363 males, mean¡ÓSD age: 51.6¡Ó11.4 years; 1750 female, mean¡ÓSD age: 48.9¡Ó11.3 years; 2353 rural and 760 urban) were recruited. Blood pressure (BP), body mass index (BMI), waist-hip ratio (WHR), smoking habits and family history of premature coronary heart disease (CHD) were documented and venous blood was obtained for fasting lipid and glucose analysis. Diabetes was considered present if the participant was under treatment with insulin or oral hypoglycaemic agents or levels of fasting blood glucose „d7.0mmol/L at recruitment time. Results: The prevalence for diabetic was 15.0% (male 15.7%; female 14.5%) and higher in rural as compared to urban (15.9%vs12.2%,p<0.05). The prevalence for obesity (BMI>30) was 13.8% (male 10.5%; female 16.2%) with higher proportion of obese subjects from rural (14.2%vs12.4%,p<0.05) compared to urban. While that for morbid obesity (BMI>35) was 4.3% (male 3.3%; female 5.0%) with more subjects with morbid obesity in the urban as compared to rural (4.5%vs4.2%,p<0.05). Conclusion: The prevalence diabetic and obesity were found to be high in the rural subjects while higher proportion of urban subjects were found to be in the morbid obesity category.


PREVALENCE OF HYPERTENSION AND DYSLIPIDAEMIA AMONG MALAYS IN RURAL AND URBAN MALAYSIA
R. Razali, F. Abd Majid, T. Tengku Ismail, A. Krishnapillai, N. Mat Nasir, A. Ramli, N. Mohd Noor Khan, H. Mohd Nawawi, K. Yusoff
Faculty of Medicine, Universiti Teknologi Mara, Shah Alam, Selangor, Malaysia

Introduction : Coronary heart disease (CHD) continues to be a leading cause of death around the globe. Risk factors for CHD including hypertension, cigarette smoking, high total cholesterol (TC) and low density lipoprotein (LDL-C); low high density lipoprotein (HDL-c) and diabetes. Objective: To investigate the proportion hypertension and dyslipidaemia among Malays in rural and urban areas in Malaysia. Methods: Cross-sectional community-based study were conducted in several urban and rural populations in Malaysia involving 3113 subjects (1363 males, 1750 female, 2353 rural and 760 urban). Blood pressure (BP) and anthropometry measurement, smoking habits and family history of premature CHD were documented. Venous blood samples were obtained from fasting subjects for lipid profile and plasma glucose levels. Hypertension was defined based on JNC VII classification of blood pressure for adults. Results: The overall prevalence of hypertension was 38.8% (40.3% male; 37.7% female) with higher percentage in rural as compared to urban population (43.8% vs 23.4%, p<0.0001). 63.5% of subjects (64.4% male; 62.7% female) were found to be mildly hypercholeterolaemic (TC ¡Ý5.2 mmol/L) with higher proportion in the urban subjects as compared to urban (68.7% vs 62.2%, p<0.05), 27.2% (25.2% male; 28.8% female) were moderately hypercholesterolaemic (TC¡Ý6.5 mmol/L) with higher proportion in the rural subjects than urban subjects (27.6% vs 25.9%, p<0.05) and 9.3% (10.3% male; 8.5% female) were severely hypercolesterolaemic (TC ¡Ý7.8 mmol/L) with higher percentage in rural subjects than urban subjects (10.2% vs 5.4%, p<0.05). The overall prevalence of low serum HDL-c (<0.9 mmol/L) was 6.4% (male 9.6%, female 4.2%). Conclusion : The prevalence of hypertension and hypercholesterolaemia were high in the both rural and urban population studied. These findings suggest the need for early prevention programs in the community to prevent coronary events.


PROPORTION OF PREHYPERTENSIVE SUBJECTS AND ASSOCIATED CORONARY RISK PROFILE AMONG MALAYS IN URBAN AND RURAL MALAYSIA
R. Razali, F. Abd Majid, A. Krishnapillai, A. Ramli, N. Mat Nasir, T. Tengku Ismail, N. Mohd Noor Khan, H. Mohd Nawawi, K. Yusoff
Faculty of Medicine, Universiti Teknologi Mara, Shah Alam, Malaysia

Introduction : JNC VII defines prehypertension as systolic blood pressure (SBP) between 120 to 139 and/or diastolic blood pressure (DBP) between 80 to 89 mmHg. Studies have shown that prehypertension is associated with increased risk of cardiovascular disease and progression to hypertension. Objective: To determine the proportion of prehypertension among adults in urban and rural Malaysia and characterize the coronary risk profiles among prehypertensive. Methods : Cross-sectional study involving 3113 subjects (2353 rural; 760 urban). Blood pressure (BP), body mass index (BMI) and waist-hip ratio (WHR) and fasting venous blood were obtained for lipid profile and glucose level. Results : PreHT were observed in 35.6% of the subjects with higher proportion in urban as compared to rural (36.2% vs 35.4%). The prevalence of hypertension was 38.8% (40.3% in male, 37.7% in female). The PreHT group had higher levels of glucose (mean±SD:5.4±2.0 vs5.0±2.3mmol/L, p<0.0001), total cholesterol (mean±SD:5.8±1.4vs5.6±1.4mmol/L, p<0.0001), triglyceride (mean±SD:1.9±1.2vs1.6±1.0mmol/L, p<0.0001), LDL-c (mean±SD:3.7±1.2vs3.5±1.2mmol/L,p<0.05) and BMI (mean±SD:26.0±5.6vs24.0±4.5kg/m2,p<0.0001) ; and had lower levels of HDL-c (mean±SD:1.26±0.4vs.32±0.4 mmol/L, p<0.05) compared to normotensive group. The rural subjects of PreHT group had higher total cholesterol (mean±SD:5.9±1.4 vs 5.6±1.2 mmol/L, p<0.05), triglyceride (mean±SD:1.9±1.2 vs 1.7±1.2 mmol/L, p<0.05) and LDL-c (mean±SD:3.7±1.2 vs 3.5±1.2 mmol/L, p<0.05) levels compared to urban but urban subjects had higher BMI (mean±SD:27.2±5.3 vs 25.6±5.3 kg/m2, p<0.0001) and waist circumference (mean±SD:87.8±11.6 vs 83.1±11.8 cm, p<0.0001). Conclusion : Perhypertension is prevalent in Malays population both in rural and urban areas and associated with adverse coronary risk profiles than normotensive subjects.


ABNORMAL SCREENING GLUCOSE CHALLENGE TEST IN PREGNANCY AND FUTURE RISK OF DIABETES IN YOUNG WOMEN
R. Retnakaran^1,2, B. Shah^2,3,4
1)Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto ²⁾Department of Medicine, University of Toronto
³⁾Department of Medicine, Sunnybrook Health Sciences Centre, Toronto ⁴⁾Institute for Clinical Evaluative Sciences, Toronto

Pregnant women are typically screened for gestational diabetes mellitus (GDM) using a 50g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) for those women for whom the GCT is abnormal. While it has long been recognized that GDM is associated with subsequent type 2 diabetes, it has recently emerged that any degree of abnormal antepartum glucose homeostasis actually predicts an increased risk of postpartum glucose intolerance. The study sought to determine whether women who have a pregnancy complicated by an abnormal GCT, but without GDM, have an increased risk of subsequent diabetes, compared to their peers without an abnormal GCT. We conducted a population-based retrospective cohort study in the Canadian province of Ontario. The study population included all women aged 20-49 years with live births between April 1999 and March 2002, excluding those with GDM or pre-gestational diabetes. Women who had an antepartum OGTT (indicative of an abnormal GCT) were matched (by age, region, socioeconomic status, and year of delivery) with up to four other women without an OGTT. The matched cohorts included 43,865 women with an antepartum OGTT and 160,065 women without. Mean age at entry was 30 years in both cohorts, and median follow-up was 6.5 years. The hazard ratio for subsequent diabetes in women with an antepartum OGTT was 2.08 (95% CI 1.93-2.23. p<0.0001). Even in the absence of GDM, an abnormal screening GCT in pregnancy is associated with an increased future risk of diabetes in young women.

 

EVALUATION OF GRAPE SEED SUSPENSION EFFECT TO GLUCOSE, INSULIN, AND SERUM TOTAL ANTIOXIDANT LEVELS AFTER ALLOXAN INJECTION IN RAT
M. Shahaboddin¹, M. Pouramir², A. Moghaddamnia², M. Rasaei³, K. Parastooei¹, A. Abbaspour^4
1)Kashan University of Medical Sciences, Iran ²⁾Babol University of Medical Sciences, Iran ³⁾Tarbiat Modares University, Iran ⁴⁾Bojnord University of Medical Sciences, Iran

Introduction: It has been reported that induction of Diabetes Mellitus is associated with increased production of Reactive Oxygen Species and depletion of the antioxidants defense systems. Grape seed have potent free radical scavengers (Proantocyanidins) and hence provide significant protection against oxidative stress. The purpose of this investigation was to examine whether grape seed plays protective role against hyperglycemia and beta-cells damages in injected alloxan rats. Methods: Black grape seeds (shahani grape) milled and dissolved in distilled water. Totally 90 rat were used and divided into three groups: 1)control 2)giving high dose grape seed(2gr/kg.bw/day) 3)low dose(1gr/kg.bw/day).Rats in 2&3 groups pretreated by grape seed’s suspension via oral gavage.Then alloxan (a classical diabetogen) injected subcutaneously. After 24h,48h,72h of alloxan injection, the animals sacrificed by decapitation and blood collected and serum glucose (by commercially kit)¸serum insulin level(by ELISA kit)and serum total antioxidant power(by FRAP assay) measured. Results: our results revealed that oral administration of high dose (2gr/kg.bw/day) grape seeds significantly inhibited the increase of serum glucose caused by alloxan(p<0.05)but in low doses this reduce wasn’t significant in 48h&72h(p>0.05).Also high and low doses grape seed cause a significant increase in serum insulin levels in pretreated rats in 24h,48h¸72h(p<0.05). Serum total antioxidant levels increased significantly (24h&48h) in rats used low doses grape seed (p<0.05) while it was not significant in other groups (p>0.05.( Conclusion: in conclusion, the study suggests that grape seeds are effective in ameliorating the oxidative damage to pancreatic tissue in experimental Diabetes Mellitus. Such effect may be related to their potent antioxidant properties.


AMELIORATE INSULIN RESISTANCE BY AQUEOUS EXTRACT OF CHLORELLA
M. Shih¹, H. Lin¹, L. Hsu¹, C. Chen¹, J. Cherng^2
1)Chia-Nan University of Pharmacy & Science, Taiwan R.O.C ²⁾National Chung Cheng Univeristy, Taiwan R.O.C

Fresh grown Chlorella has been shown to lower serum cholesterol levels, boost immune function and ameliorate hyperglycemic state of STZ mice. Here, we propose a possible role for insulin sensitizing effects of aqueous extract of Chlorella (insuplus). Diabetic db/db mice and differentiated 3T3-L1 cells (adipocytes) were used as insulin resistance models. Mice were treated with insulin (2.5 IU/kg) or insuplus (100 mg/kg) and their plasma blood glucose levels were monitored for 24 hours. Differentiated 3T3 cells were co-cultured with LPS-stimulated macrophage media (conditioned media) for 12h. Non-esterified fatty acid (NEFA) production was measure in the presence of insulin (1 pM) or insuplus (2 mg/ml). Effects of insuplus on expression of PPAR-gamma, is known as the transcriptional factor for regulating fatty acid binding protein in adipocytes, was also investigated under the same treatment. Plasma glucose levels were not affected by administration of insuplus in normal mice, whereas the levels were significantly suppressed for as long as 12h in db/db mice. Inhibitory effect of insulin on NEFA production was dininished in the condition media treated adipocytes. However under the same condition, the inhibition of NEFA production was resumed in cells co-treated with insuplus. Expression of PPAR-gamma was diminished in the condition media treated adipocyte, however the presence of insuplus prevented the loss of PPAR-gamma gene. Accumulation of fatty acid has been shown to cause insulin resistance. In conclusion, hypoglycemic effect of Chlorella is at least partly mediated through removing fatty acids from the circulation.


MONEY HANDLING INFLUENCES BMI: A SERVEY OF CASHIERS
K. Shurpali¹, S. Karve¹, M. Jog¹, M. Watve^1,2
1)Department of Microbiology, Abasaheb Garware College, Pune, India. ²⁾Anujeeva Biosciences Pvt Ltd

Money is a recent phenomenon in a evolutionary history of man and therefore no separate brain centre to handle money has evolved. The area in the orbitofrontal cortex activated by food reward and money reward is shown to be the same. In an experimental set-up, hunger was demonstrated to influence money related decisions and money related thoughts to influence hunger. This suggests that there could be a neuronal cross-talk between food and money and changing attitudes and behavior related to money and wealth could be a significant factor in shaping the current obesity epidemic. In order to test the hypothesis, we conducted a servey of 203 cashiers working in different work set-ups viz bank cashiers (51), shop cashiers (64) and shop owners (88). Personal history, job history, medical history, BMI and exercise schedule were recorded. The BMI correlated with years of service as cashier even after correcting for age and exercise. Male but not female cashiers who had ownership over the money had a significantly higher mean BMI than salaried cashiers. Among salaried cashiers of both sexes, bank cashiers whose daily cash handling is one or two orders of magnitude more than shop cashiers, had a significantly higher BMI. The effects of amount of money handled per day, years of service as cashier and ownership over the money handled could be shown to influence BMI independent of each other. The results support the hypothesis that the physical as well as mental act of money handling influences obesity.


APPROACHES TO INITIATION OF INSULIN THERAPY IN PATIENTS WITH TYPE 2 DIABETES AND RESULTING OUTCOMES AT 12 MONTHS IN FOUR EUROPEAN COUNTRIES: DATA FROM THE INSTIGATE STUDY
A. Simpson¹, H. Smith², C. Nicolay³, S. Jones⁴, C. Castell⁵, A. Goday^6
1)European Medical, Eli Lilly, Surrey, UK ²⁾European Outcomes Research, Eli Lilly, Surrey, UK ³⁾European Statistics, Eli Lilly, Bad Homburg, Germany ⁴⁾The Academic Centre, James Cook University Hospital, Middlesborough, UK, ⁵⁾Department De Salut, Generalitat De Catalunya, Barcelona, Spain ⁶⁾Servicio De Endocrinologia, Hospital Del Mar, Barcelona, Spain

INSTIGATE is a prospective observational study investigating patients with type 2 diabetes initiating insulin during usual care. This abstract describes clinical and patient reported outcomes over the year following insulin initiation. 1153 patients enrolled in the 6 month study, reported here are data from 619 patients participating in an 18 month extension. Patient numbers (original-study/extension) were; Germany (256/139), Greece (263/237), Spain (207/173), UK (251/70), France (177/0). Basal-only was the most common starting regimen (45%). German patientdinitiated more intensive regimens; 78% started basal-bolus or short-acting regimens. In Spain more patients initiated basal-only regimens (68%). Overall, 12% patients changed regimen in the first year. There was reduction in mean HbA1c after 3 months, then little change thereafter. By 12 months only Germany had mean HbA1c ¡Ü7% (6.65%), UK had highest mean HbA1c (8.52%). BMI increased between visits; overall, the mean intra-patient increase was +0.54kg/m2 over the first year of insulin therapy. The percentage of patients who reported symptoms of hypoglycaemia after insulin initiation was highest in UK (49% baseline to 6 months, 40% 6 to 12 months) and lowest in Spain (20% baseline to 6 months, 10% 6 to 12 months). Median health related quality of life (HRQoL) (EuroQol-VAS) scores were 60 at baseline and 75 at 12 months. The median intra-patient improvement was 10 points. Median intra-patient changes were highest in Greece (+10) and lowest in UK (¡À0). Overall, glycaemic control and HRQoL improved following insulin initiation. Treatment approach and outcomes differed between countries. Few changes were made to starting regimens.


COST AND RESOURCE USE IN THE 12 MONTHS FOLLOWING INSULIN INITIATION IN FOUR EUROPEAN COUNTRIES: DATA FROM THE INSTIGATE STUDY
H. Smith¹, C. Nicolay², A. Simpson³, C. Castell⁴, S. Jones⁵, A. Goday^6
1)European Outcomes Research, Eli Lilly, Surrey, UK ²⁾European Statistics, Eli Lilly, Bad Homburg, Germany ³⁾European Medical, Eli Lilly, Surrey, UK ⁴⁾Department De Salut, Generalitat De Catalunya, Barcelona, Spain ⁵⁾The Academic Centre, James Cook University Hospital, Middlesborough, UK ⁶⁾Servicio De Endocrinologia, Hospital Del Mar, Barcelona, Spain

Iintigate is a prospective observational study investigating patients with type 2 diabetes who initiate insulin during usual care. This abstract reports resource use and direct costs of care for type 2 diabetes before and 12 months after insulin initiation. Direct costs of diabetes care were calculated using resource use data and local unit costs (2006). 1153 patients enrolled in the 6 month study, reported here are data from 619 patients participatingin an 18 month extension . Patient numbers (6 month study/extension) were; Germany (256/142), Greece (263/237), Spain (207/173), UK (251/70), France (177/0.( Basal-only was the most common starting regimen (45%) although the choice of starting regimen varied between countries. Overall, 12% patients changed regimen in the first year. Mean insulin dosage at baseline and 12 months was 0.32IU/kg and 0.47IU/kg respectively (mean 0.147IU/kg increase). Per patient, mean total contacts with health care professionals (HCPs) was 9.1 in the 6 months prior to baseline, 11.9 from baseline to 6 months, and 6.2 from 6 to 12 months. Median total costs of diabetes care for the 6 month periods prior to baseline, 6 months and 12 months were €482, €692, €545 respectively. Germany had the highest median total cost in the 6 to 12 month period (€767) and Greece the lowest (€423). The cost drivers were insulin (€193) and blood glucose monitoring (BGM) (€131(. Following insulin initiation mean cost per patient increased driven by insulin and BGM. Contacts with HCPs and costs had fallen from 6 to 12 months.


CARDIOVASCULAR AUTONOMIC NERVOUS CONTROL IN A RAT MODEL OF DIET-INDUCED OBESITY
A. Soares Leopoldo¹, P. Pereira Junior², A. Lima-Leopoldo¹, E. Medei², D. Salome De Campos¹, J. Raimundo³, R. Sudo³, G. Zapata-Sudo³, J. Nascimento², A. Cicogna^1
1)Departamento De Clínica Médica, Faculdade De Medicina, Universidade Estadual Paulista “Julio De Mesquita Filho”, Botucatu, Sao Paulo, Brasil. ²⁾Instituto De Biofísica Carlos Chagas Filho, Universidade Do Brasil, Rio De Janeiro, Brasil.
³⁾Departamento De Farmacologia Bsica E Clínica. Universidade Do Brasil, Rio De Janeiro, Brasil

The purpose of the study was to investigate the cardiac autonomic function in a rat model of diet-induced obesity. We also evaluated if the obesity is associated with abnormalities of electrocardiogram indexes (ECG), QT interval, heart rate variability (HRV) and vascular reactivity. Male 30-day-old Wistar rats were fed standard (C) and high-fat diet (Ob) for 19 weeks. Cardiac autonomic control was assessed by electrocardiogram in vivo and spectral analysis of heart rate variability. The vascular reactivity in the aorta was evaluated by vasocontriction and vasodilation responses to phenylephrine and to acetylcholine, respectively. After 19 weeks, compared with C rats, the Ob rats had increased total body fat, however, the final body weight (FBW), systolic blood pressure (SBP), area under the curve for glucose (AUC), calorie intake (CI) and heart weight-to-final body weight ratio (HW/FBW) were similar between rats. Obesity did not alter the electrocardiogram indexes and cardiac sympathetic activity. There were no differences in the vasorelaxation responses to acetylcholine and the maximal contractile response of the thoracic aorta to phenylephrine between groups, however, the EC50 showed a decrease in the sensitivity to phenylephrine in obese rats. The present work indicates that obesity does not impair both the endothelium-dependent relaxation and cardiac sympathetic activity. However, the obesity promotes a decrease in the sensitivity to phenylephrine in the aorta from obese animals.


IMPAIRED L-TYPE CA2+ CHANNELS CONTRIBUTES TO MYOCARDIAL DYSFUNCTION IN OBESE RATS
A. Soares Leopoldo¹, A. Lima-Leopoldo¹, M. Sugizaki¹, A. Ferreira Do Nascimento¹, D. Salome De Campos¹,
D. Tomaz Da Silva¹, P. Silva¹, C. Regina Nogueira¹, C. Padovani², A. Cicogna^1
1)Department of Clinical and Cardiology, School of Medicine, Unesp- State University Julio Mesquita Filho, Botucatu, Sao Paulo, Brazil. ²⁾Department of Biostatistics, Institute of Biological Sciences, Unesp- State University Julio Mesquita Filho, Botucatu, Sao Paulo, Brazil

Depressed function of L-type Ca2+ channels is among the cellular changes that may contributes to the mechanical dysfunction. The purpose of the study was to investigate the participation of the L-type Ca2+ channels on cardiac dysfunction induced by obesity. We tested the hypothesis that Wistar obese rats present impaired contractile response related to lower L-type Ca2+ channels activity. Male 30-day-old Wistar rats were fed standard (C) and hypercaloric diet (Ob) for 15 weeks. The body fat was measured from the sum of the individual fat pad weights and the obesity was defined as increased of the adiposity index. Cardiac function was evaluated by isolated papillary muscle preparation and assessed under basal conditions and after inotropic and lusitropic maneuvers: post-rest contraction and elevation in extracellular Ca2+ concentration. Futhermore, to determine whether impaired influx of Ca2+ ions through voltage-dependent L-type Ca2+ channels plays an essential role in cardiac excitability and in coupling excitation to contraction, a specific blocker, diltiazem, was used. Compared with C rats, the Ob rats had increased in the final body weight, body fat and glucose intolerance; however, there was no difference in systolic blood pressure. The Ob-muscles presented similar baseline and maximum force, but the myocardial responsiveness of developed tension (DT) was significantily diminished in obese myocardium after cessation of the stimulus. The diltiazem promoted a higher blockade on DT in Ob when compared to C. Therefore, the myocardial dysfunction observed by obesity suggests that this impaired contractile may be related to lower L-type Ca2+ channels function.


MYOCARDIAL DYSFUNCTION INDUCED BY OBESITY IS RELATED TO CALCIUM HANDLING ABNORMAL
A. Soares Leopoldo¹, A. Lima-Leopoldo¹, M. Sugizaki¹, A. Ferreira Do Nascimento¹, R. Azevedo Melo Luvizotto¹, D. Salome De Campos¹, S. Assis De Oiveira Junior¹, C. Regina Nogueira¹, C. Padovani², A. Cicogna^1
1)Department of Clinical And Cardiology, School of Medicine, Unesp- State University Julio Mesquita Filho, Botucatu, Sao Paulo, Brazil ²⁾Department of Biostatistics, Institute of Biological Sciences, Unesp- State University Julio Mesquita Filho, Botucatu, Sao Paulo, Brazil.

Several mechanisms have been proposed to contribute to the cardiac dysfunction in obesity models as reduced myofilament calcium (Ca+2) sensitivity, alterations in calcium handling proteins and -adrenergic receptors. Nevertheless, whether these factors to play a critical role in development of obesity-related myocardial dysfunction are still not clear. The purpose of the study was to investigate whether the obesity-induced short-term exposure results in cardiac dysfunction. Furthermore, we also evaluated whether this alteration in obese rats is related to abnormal calcium handling and -adrenoceptor system. Male 30-day-old Wistar rats were fed standard (C) and hypercaloric diet (Ob) for 15 weeks. Obesity was defined as increased of percentage of body fat in carcass. Cardiac morphology and function was evaluated by histology and isolated left ventricle papillary muscle, respectively. Analysis of the isolated papillary muscle was assessed under basal conditions and after inotropic and lusitropic maneuvers: post-rest contraction (PRC), elevation in extracellular Ca2+ concentration, and during -adrenergic stimulation with isoproterenol. Compared with C rats, the Ob rats had increased body fat and glucose intolerance; however, there were no differences in the final body weight and systolic blood pressure. The Ob-muscles developed similar baseline and maximum force, but the myocardial responsiveness to stimulus PRC and increased extracellular Ca2+ was compromised. The response to -adrenergic stimulation was similar in both groups. Obesity promotes cardiac dysfunction by changes in intracellular Ca2+ handling, probably due reduced cardiac SERCA2 activity, diminished intracellular release Ca2+ by ryanodine receptors (RyR2) and/or reduced myofilament Ca+2 sensitivity.


THE EFFECT OF ANGIOTENSIN II ON THE CD40 AND CD40 LIGAND EXPRESSIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELL LINES
A. Sonmez¹, T. Dogru², A. Pekel³, M. Sarper⁴, P. Elci⁴, F. Avcu^4,5, I. Tasci⁶, U. Musabak³, R. Ilikci³, G. Erdem⁶, M. Yilmaz⁷, A. Ural^4,5
1)Gulhane School of Medicine, Department of Endocrinology and Metabolism, 06018 Etlik Ankara Turkey ²⁾Department of Gastroenterology ³⁾Department of Immunology ⁴⁾Medical and Cancer Research Center ⁵⁾Department of Hematology ⁶⁾Department of Internal Medicine ⁷⁾Department of Nephrology

Introduction: CD40 Ligand (CD40 L) is a transmembrane glycoprotein which has a prominent role in the development of atherosclerosis and its complications. CD 40 L is mainly secreted by the activated platelets and causes its proinflammatory and atherogenic effects by interacting with its receptor CD40. Angiotensin II (AII) is also a proinflammatory and proatherogenic molecule which uses similar secondary messengers as of the CD40/CD40L interaction. It has recently been reported that the vascular endothelium is a source of both CD40 L and its receptor CD40. So far there has been no data about any interaction between angiotensin II and CD40/CD40 L expression on the endothelial cells. Methods:Human Umbilical Vein Cell (HUVEC) lines were incubated in appropriate media with different AII concentrations (10-6, 10-9,10-12 ug/ml), for different periods (12, 24, 48, 72 hours). The surface expressions of CD40 and CD40 L were searched with flowcytometry by using mouse antihuman monoclonal antibodies and by real time PCR.. Results: CD40 and CD40L expressions in HUVEC lines were shown by both flowsytometry and RT-PCR. Incubation with AII in several concentrations and periods did not cause any significant alteration on the expressions of CD40 and CD40L. Conclusion:It may be implicated from these results that the proinflammatory and proatherogenic effects of AII are not related to the altered expressions of CD40 or CD40 L on the endothelial cells. Further studies have to be performed in order to elucidate the mechanism of any interaction between A II and CD40/CD40L system in post-receptor levels.


LIPID BASED NANOPARTICLES (LBN) AS A NOVEL STRATEGY FOR ORAL INSULIN DELIVERY
S. Souto, S. Martins, E. Souto
Department of Pharmaceutical Technology, Faculty of Health Sciences, Fernando Pessoa University ²⁾Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto

Insulin therapy has being performed parenterally, which is a low patients’ compliance administration route. Lipid-based nanoparticles (LBN) are submicron carriers consisting of biocompatible and biodegradable lipids suitable for peptide administration. Development of an improved oral insulin formulation is of major relevance for daily management of diabetes mellitus, to overcome the problem of daily subcutaneous injection. LBN protect insulin against harsh enzymatic and acidic environment of gut, enhancing its transmucosal transport, by mucoadhesion, internalization via Peyer’s patches and absorption. Insulin delivery by LBN is discussed, addressing the development of novel mucoadhesive formulations to increase the residence time of insulin near intestinal absorptive cells. The role of absorption enhancers (bile salts, surfactants and cyclodextrins) is also addressed .Insulin-loaded cetyl palmitate LBN were produced by a modified double emulsion technique, and further administered to diabetic rats in accordance with FELASA and European Union (Council Directive 86/609/EEC). Plasma glucose levels were plotted against time evaluating the cumulative hypoglycemic effect over time.Insulin-loaded LBN decreased glycemia in rats in comparison with oral solution and empty LBN. The hypoglycaemic effect was biphasic, i.e. initial peak at 3.5 h (burst release) with a decrease of 20% of the initial glucose level. Prolonged release was observed up to 24 h. The solid matrix of LBN was able to protect insulin against chemical degradation in the gut and enhance insulin intestinal absorption. The relative pharmacological bioavailability of insulin was approx. 5% when administered by means of LBN, whereas below 2% when delivered as oral solution.


RELATIONSHIP BETWEEN HYPERURICEMIA AND METABOLIC SYNDROME IN AN OBESE POPULATION
S. Souto¹, J. Mesquita¹, P. Freitas^1,2, A. Varela^1,2, M. Matos^1,2, F. Correia^1,3, M. Ferreira⁴, D. Braga¹, D. Carvalho^1,2, J. Medina^1,2
1)Department of Endocrinology, Sao Joao Hospital, Porto, Portugal ²⁾Faculty of Medicine, Porto University, Portugal
³⁾Faculty of Food And Nutritional Sciences, Porto University, Portugal ⁴⁾Department of Mathematics, Minho University, Braga, Portugal

Hyperuricemia is associated with abnormalities of metabolic syndrome(MS), namely obesity, glucose intolerance, hypertension, dislipidemia and cardiovascular disease. Hyperuricemia has been suggested to play a causal role for the MS. Hyperinsulinemia caused by insulin resistance can induce low excretion type hyperuricemia. However, visceral fat accumulation itself causes the hypersynthetic type hyperuricemia through increased fatty acid influx into the liver. Aims:To determine hyperuricemia and MS prevalence in obese population and to evaluate the association between serum uric acid levels(UA) and MS components. Study design:277 patients(30men,247women) were evaluated in their first morbid obesity appointment, regarding anthropometric variables, blood pressure, fasting plasma glucose(FPG) levels, LDL-cholesterol, HDL-cholesterol, triglycerides and UA concentrations. MS was defined using IDF-2005 criteria. Hyperuricemia was defined as ¡Ý7.0mg/dL (men) and ¡Ý6.0mg/dL (women). Subjects taking hypouricemic agents and/or alcohol consumption were excluded. Results were expressed as mean¡ÀSD and relative frequency. Pearsons correlation coefficients were obtained for each of MS components and respective UA concentration. Results:The mean age of men was 40.97¡À13.44 years old, having a mean BMI of 44.72¡À5.55Kg/m2. Women sample was 41.0¡À11.70 years old (BMI=43.75¡À7.31Kg/m2). Hyperuricemia prevalence was 20.57%(40.0% men,18.21% women). MS prevalence was 60.28%(86.66% men,57.08% women). Among men, UA was positively correlated with waist circumference (WC)(r=0.425). No correlations were found among other MS components. Among women, positive correlations were shown for UA with BMI, WC, hypertension and triglycerides. BMI(r=0.36) and WC(r=0.43) were most strongly correlated with UA. UA was negatively correlated with HDL-cholesterol. Conclusions:Hyperuricemia and MS prevalence was high. Among women, UA was markedly associated with MS and its components.


DIABETES MELLITUS AND NEOVASCULAR GLAUCOMA
D. Stojsic, J. Stojsic, M. Vejnovic
General Hospital, Sombor, Serbia

Ocular complications from diabetes mellitus represent a significant public health problem. In the diabetic patients only 5% of the blindness is due to neovascular glaucoma. While this percentage is small, diabetes mellitus(DM) is probably the most common cause of neovascular glaucoma. Aim:To evaluate incidence of the neovascular glaucoma in group of patients with diabetes mellitus. Materials and Methods: This study includes randomly selected outpatient diabetic patients (n-334; female ¡V170, male-164); type 1 DM (n-41, aged 37.3„b12.9; with mean duration of DM 9.6„b7.0); type 2DM (n-293; aged 58.9„b8.7; mean duration of DM 5.7„b3.7), examined during two-year period (2004-2005). We measured intraocular pressure (IOP) with applanation tonometry, for neovascular vessels examination we used gonioscopic examination and biomycroscope. We used direct ophthalmoscopy to examine fundus oculi. Results: In our study 5 (1.5%)diabetic patients were found with neovascularisation. We have correlated neovascularisation of iris and duration od DM and have correlated neovascularisation of iris with type of DM. We did not find statistically significant correlation between duration of DM and neovascular glaucoma (C=0.1147; X2=4.4563; p>0.05) and between type of DM and neovascular glaucoma (C=0.07646; X2=0.2812; p>0.05.( Conclusions: Our results failed to confirm an association between of type and duration of diabetes mellitus and neovascular glaucoma, but clinicians should be aware of possibility of the development neovascular glaucoma in diabetic patients.


ACE GENE POLYMORPHISMS, ANTHROPOMETRICAL AND BIOCHEMICAL PARAMETERS IN GROWING-SLIM FEMALES
P. Suchanek^1.2, J.A. Hubacek^1.2, I. Kralova Lesna^1.2
1)Institute for Clinical and Experimental Medicine, Prague, Czech Republic ²⁾Cardiovascular Research Centre, Prague, Czech Republic

Introduction: Many genes have been implicated in determination of obesity, but our knowledge’s about the genes responsible for individual differences in weight loss after physical intervention are poor. One of the candidate genes is a gene for angiotensine converting enzyme (ACE) ant its insertion/deletion (I/D) polymorphism. Aim: The aim of the study was analyze ACE I/D variant in 93 unrelated non-diabetic females. There were 17 II homozygotes and 74 D allele carriers. Material and methods: DNA was isolated from frozen EDTA blood and I/D polymorphism was analyzed using two steps PCR. Before and after 9 weeks of trainigs programme, biochemical (plasma lipid levels) and anthropometrical measurements were performed. The participants were advised (and supervised) to sustain a heart rate of 115-145 beats (according to age) per minute within 60 minutes of exercise 3 times per week. Results: The changes between anthropometrical and lipid parameters did not differ between females with different ACE genotypes. Nevertheless, in D allele carriers, plasma levels of TG decreased after 9-weeks physical training, but II homozygotes have higher plasma levels of TG after intervention (p= 0.02(. Conclusion: ACE I/D variant has no effect on anthropometrical and most biochemical parameters changes after physical training. But, in contrast to the D allele carriers, I/I homozygotes have after training higher plasma TG levels and their energy supply for muscle performance could be so improved. Supported by project No. 9393-3, MH CR.


A NEW NOVEL MUSCLE STIMULATOR AIMS AT AUGMENTING PERIPHERAL BLOOD SUPPLY TO DIABETIC WOUND PATIENTS
J. Tamir¹, M. Lipo^2
1)Halstead Hospital, Kansas, USA ²⁾Private Wound Care Clinic, Jerusalem, Israel

Background: Peripheral Vascular disease (PVD) is a common condition especially in diabetic patients. When severe PVD is complicated with a wound the potential for limb and life threatening complications is remarkably elevated. Flowaid FA-100 is an external, portable, neuro-stimulator that activate the calf muscles, producing a peristaltic wave that mimics the natural muscle pump. It enhances arterial blood supply and venous return. Purpose: To present the clinical effects of Flowaid FA-100, an external musculo-stimulator device, on diabetic patients with ischemic wounds. Methods: Flowaid FA-100 was used for 2 hours daily on 4 patients with chronic foot ulcers. We describe the clinical outcome and the Ankle-Brachial Index (ABI) scores in those patients. Results: The average ABI rose significantly in all the patients and the wounds decreased by at least 60% in size. One leg with severe infection that was scheduled for at amputation was salvaged. Conclusion: Flowaid FA-100 is a new technology with a potent ability to enhance arterial blood flow in ischemic patients by stimulating the native musculature - vascular systems. It is beneficial as an adjuvant treatment in diabetic patients with arterial insufficiency.


DIURETICS AND HYPERTENSION IN THE ELDERLY; IMPLICATIONS FOR SLEEP QUALITY AND COGNITION.
D. Tarmey¹, A. Fawcett², A. Telfer¹, R. Nicolson^1
1)University of Sheffield, Sheffield, United Kingdom ²⁾Swansea University, Swansea, United Kingdom

Diuretic medications are currently the drugs of choice for hypertension in the elderly due primarily to their efficacy, ease of use, perceived side effect profile and cost. Although other classes of antihypertensive are both available and suitable for older adults these are less routinely used in frontline therapy. At present it is unclear if diuretic medication has any effect on the incidence of nocturia, sleep quality and subsequent cognitive functioning; or if patients with impaired glucose regulation differ from ‘normal elderly’ in their response. Methods: 189 community dwelling older adults matched for age and lifestyle factors took part in tests of cognitive function as part of the South Yorkshire Ageing Study (SYAS), a longitudinal interdisciplinary study of ageing in northern England. Results: The use of diuretic medication was associated with an increased incidence of nocturia (p <0.001) and a reduced number of hours sleep each night (p = 0.01). Participants taking diuretic medication also showed greater impairment on tests of fluid (p = 0.008) but not crystallised cognitive abilities. There were no significant differences in terms of effects between diabetic and non-diabetic individuals.
Conclusion: Diuretic medications are associated with an increase in the frequency of nocturia with the resulting sleep deprivation having the potential to cause functional difficulties in older adults, specifically in tasks with significant speed of processing and memory demands. Our findings raise questions over medication use and patient education.


PREVALENCE OF METABOLIC SYNDROME IN ASIAN MALAYS IN RURAL AND URBAN MALAYSIA
T. Tengku Ismail, R. Razali, F. Abd Majid, A. Krishnapillai, A. Ramli, N. Mat Nasir, N. Mohd Noor Khan, H. Mohd Nawawi, K. Yusoff
Faculty of Medicine, Universiti Teknologi Mara, Shah Alam, Selangor, Malaysia

Introduction : Metabolic Syndrome (MS) is a constellation or clustering of metabolic abnormalities which includes obesity, insulin resistance, dyslipidaemia and elevated blood pressure. It is associated with increased risk of cardiovascular morbidity and mortality. Objective : To compare the proportion of MS according to International Diabetes Federation (IDF) definition and NCEP ATP III using waist circumference cut-offs for Asian (>90cm in male & >80 cm in female) among Malays in rural and urban population in Malaysia. Methods : Cross-sectional community-based study were conducted in several urban and rural populations in Malaysia. 3113 subjects (1363 males, mean±SD age: 51.6±11.4 years; 1750 female, mean±SD age: 48.9±11.3 years; 2353 rural and 760 urban) were recruited. Blood pressure (BP), body mass index (BMI), waist-hip ratio (WHR), smoking habits and family history of premature coronary heart disease (CHD) were documented and venous blood was obtained for fasting lipid and glucose analysis. Results : The prevalence of MS according to IDF definition was 20.3% (27.9% in male; 14.4% in female) and 16.5% (22.7% in male; 11.6% in female) according to NCEP ATP III. The proportion of MS by both IDF definition and NCEP ATP III in the rural was significantly higher as compared to urban population (21.2% vs 17.3%, p<0.05 ; 17.2% vs 14.1%, p<0.05 respectively(. Conclusion : Prevalence of MS in the studied Malay population is high. The prevalence of MS in rural was found to be higher than that in the urban population by both IDF definition and NCEP ATP III.


HYPERTENSION, DM TYPE 2 AND OBESITY IN POSTMENOPAUSAL WOMEN WITH CARDIOVASCULAR DISEASES
L. Vatca¹, D. Zdrenghea^2
1)University of Oradea, Romania ²⁾University of Medicine and Pharmacy Cluj-Napoca, Romania

The aim of our study was to evaluate mortality and also prevalence of cardiovascular risk (CVR) factors in postmenopausal women with CVD. Method Until September 2007 we included in this screening 200 postmenopausal women with different forms of CVD-hypertension, ischemic heart disease ,stroke and heart failure Each group included 50 women .For all of them we determined: weight, height, BMI, fasting glucose, and total cholesterol. From January until May 2008 we reevaluated these women for the same parameters. Results :In the group with hypertension none of them died, none was smoker, diabetes mellitus (DM) type 2 prevalence’s was 16%, 90% for overweight and obesity and 68% for hypercholesterolemia. In the ischaemic heart disease group during a year of follow-up, one died, 2 had pulmonary edema, 3 rithm disturbances and 10 unstable angina. Prevalence for smoking was 6,12%, 38% for DM type 2, 26% for hypertension, 80% for overweight and obesity and 52% for hypercholesterolemia .In the group of women with heart failure after a year of surveillance 5 died and the prevalence for CVR factors was 0% for smoking, 80% for obesity and overweight, 34% for hypercholesterolemia, 40% for DM type 2, and 68% for hypertension. For those who were included in the group with stroke none was smoker,26% had DM type 2, 72% were overweight or obese, 48% of them had hypercholesterolemia and 68% hypertension. After a year 5 women died Conclusions: 1.Postmenopausal women with heart failure and stroke had the worst outcome; in these groups DM type 2 and hypertension were highly prevalent. 2.Postmenopausal women with hypertension were mainly obese or overweight. 3.Postmenopausal women with ischemic heart diseases had a great number of hospitalizations; in this group all cardiovascular risk factors can be identified with a high prevalence.


PARTICULAR ASPECTS OF CARDIOVASCULAR RISK FACTORS IN POSTMENOPAUSAL WOMEN
L. Vatca¹, D. Zdrenghea^2
1)University of Oradea ²⁾University of Mecicine and Pharmacy Cluj-Napoca, Romania

Cardiovascular diseases (CVD) are the leading cause of mortality both in men and women In Europe, about 55% of all females deaths are caused by CVD. After menopuause women with untreated risk factors are vulnerable to develop myocardial infarction, heart failure and sudden cardiac death. Data about prevalence of cardiovascular risk factors in postmenopausal women are few. The aim of this study was to evaluate the prevalence of cardiovascular risk factors in this population and also the dynamic of the prevalence during a year of follow-up. Method Until September 2007 we included in this screening 200 postmenopausal women-for all of them were determined:weight, height, BMI, fasting glucose, total cholesterol,HDL cholesterol, LDL-cholesterol and tryglicerides.From january until may 2008 we reevaluated these women for the same parameters. Results In 2007 prevalence for smoking was 6,5%, for diabetes mellitus tipe 2 was 14%, for hypercholesterolemia 65,5%,for hypertrigliceridemia 44,5%, for overweight and obesity (BMI>26) 75,5% and for hypertension 58%.For the same risk factor, in the same order, their prevalence in 2008, were:6,28%, 17,8%, 63,1%, 42,8%, 84,2% and 64% Conclusions: 1.Cardiovascular risk factors in postmenopausal women are highly prevalent; this is a population with a high risk for cardiovascular diseases 2.Some of cardiovascular risk factors have an important increasing in their prevalence: diabetes mellitus, hypertension and overweight and obesity. 3.These results demonstrates that it is mandatory to initiate profilactic programs for cardiovascular disease in this group of women.


DIETARY NUTRIENTS AND HYPERTENSION AMONG URBAN SCHOOL CHILDREN
A. Vergara-Castaneda ², L. Castillo-Martinez², A. Orea-Tejeda², E. Colin-Ramirez², P. Clark-Peralta¹, J. Talavera-Pina^1
1) Universidad Nacional Autónoma de México, DF. México ²⁾Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, DF, México

Objective: To determine if dietary nutrients and blood pressure is associated with the consumption of folic acid in school children. Design: 809 children were assessed in 10 different public schools in México city. Blood pressure was assesed according to the American Pediatric Academy. A 24-hour intake recall was obtained. High folate group (HFG) had a folate intake greater than the recommended daily allowance (boys, ≥;200 µg/d; and girls, ≥;180 µg/d) and the low folate group (LFG) had a folate intake less than the recommended daily allowance. Specific nutrients were also computed as intake per 1000 kcal. Results: Mean age was 9.5 years old, 52.9% were boys and 86.5% belong to the LFG. Systolic blood pressure was significantly higher in the LFG vs the HFG (boys: 111.7 vs. 105.7; girls 107.6 vs. 102.2 mmHg, p<0.05). The difference in systolic blood pressure was not significant. The LFG had significantly lower intakes of fiber (5.6 vs. 7.8 g, p=0.007), potassium (984 vs. 1317 mg/1000 kcal, p=0.033) and magnesium (72.6 vs.98.4 mg/1000 kcal, p=0.009). There were no differences between sodium intake per 1000 kcal. Conclusions: Among school children at riskfor hypertension, blood pressure was lower in those with higher intake of folic acid and a combination of nutrients, includig potassium, magnessium. The results of this investigation indicate that diet patterns - diets deficient in multiple nutrients- may contribute to higher BP levels in urban school children, putting them at risk for the development of hypertension.


BODY MASS INDEX AND OBSTRUCTIVE SLEEP APNEA SYNDROME
M. Viana¹, J. Mesquita², P. Azevedo¹, M. Ferreira³, M. Rodrigues E Rodrigues^1
1)Department of Otorrhinolaringology, Pedro Hispano Hospital, Matosinhos, Portugal ²⁾Department of Endocrinology, Sao Joao Hospital, Oporto, Portugal ³⁾Department of Mathematics, Minho University, Braga, Portugal

Introduction: Overweight is a strong risk factor for Obstructive Sleep Apnea Syndrome (OSAS). Aims: To determine whether body mass index (BMI) is correlated to apnea hypopnea index (AHI), neck circumference (NC) or Epworth sleepiness scale (ESS). To access if there is a correlation between AHI and NC or ESS. To evaluate if IMC in patients with roncopathy is significatively different from IMC in patients with OSAS. Design and Methods: We evaluated a total of 70 adult patients (52 men and 18 women) referred to an Otorrhinolaringology appointment at Pedro Hispano Hospital because of snoring. BMI, NC and ESS were determined. All patients underwent conventional nocturnal polysomnography. The Pearson¡¦s correlation coefficient was used to determine the strength of the linear relationship between variables and Student¡¦s t-test was used to compare independent samples. Results: The patients had mean age of 48,8„b11,0 years and mean BMI of 29,0„b3,9Kg/m2; 85,2% of the patients were overweight. 33,8% of the patients had roncopathy, 35,4% had mild OSAS, 15,4% had moderate OSAS and 15,4% had severe OSAS. BMI was positively correlated with AHI (r=0,40; p<0,01) and with NC (r=0,62; p<0,01). There was a significant difference in IAH between men and women (p<0,01) and a significant difference in BMI between snores and subjects with OSAS (p<0,05). There were no other statistically significative correlations between the variables evaluated in this study. Conclusions: Considering the large number of patients who are snores, the determination of BMI can be useful in defining patients with higher risk of OSAS.


OVERWEIGHT AND OBESITY IN SCHOOLCHILDREN LIVING IN URBAN AND RURAL AREAS IN BULGARIA – RISK FACTORS FOR ARTERIAL HYPERTENSION
S. Vladeva, P. Gatseva
Medical University, Plovdiv, Bulgaria

Background: Incidence of overweight and obesity among Bulgarian children increases in the last 20 years. Epidemiological studies of children reveal connection between imbalanced nutrition, overweight and metabolic syndrome. Aim: To assess incidence of overweight and obesity among urban and rural schoolchildren in Bulgaria and to evaluate the risk for arterial hypertension in them. Subjects and methods: The study included 481 children aged 8-15 from an urban area and 425 schoolchildren of the same age, living in rural area. Body mass index was estimated using Cole's criteria. The blood pressure of the children was taken and compared with the reference values for their age group. Results: 20,2% of the urban schoolchildren and 17,4% of the rural children had overweight and obesity. 10,2% of urban pupils and 8,5% of rural children had higher blood pressure compared with the reference values. 41,2% of the urban overweight and obese children were with arterial hypertension and the relative risk was 6,216 (95% CI 4,716-8,192), P<0,0001 with significant positive correlation (r= +0,52). 28,4% of the rural children with overweight and obesity were with high blood pressure and relative risk was 6,641 (95%CI 3,596-12,264), P<0,0001 with moderate positive correlation (r= +0,37). In conclusion, there is a great cardiovascular risk for overweight and obese pupils, living in urban and rural areas. Òhis alarming fact requires prophylactic programs for risk groups. It is necessary to elaborate an adequate educational program for healthy nutritional behaviour and physical activity purposely reducing health risk in schoolchildren.


DYNAMICS OF THE EATING BEAHAVIOUR AND MEDIATORS OF THE ENERGY METABOLISM DURING OBESITY TREATMENT
G. Volkova E.¹, T. Romantsova I.¹, T. Voznesenskaya G.^2
1)Department of Endocrinology, Moscow Medical Acedemy, Moscow, Russian Federation ²⁾Department of Neuroology, Moscow Medical Acedemy, Moscow, Russian Federation

Objective: to determine the dynamics of the eating behavior and insulin, leptin, GH during obesity treatment. Materials and methods: 80 patients came under examination - with age in the range of 21 – 44 (33,6±7,8), weight index - 37,1±5,6 kg/m². Eating behavior was assessed by Stunkard threefactor questionnaire, insulin, leptin, GH were evaluated. Patients were divided into 2 groups. The first group received cognitive-behavioral therapy and pharmaceutical treatment (subitramine). The second group received only cognitive-behavioral therapy. Results: The evaluation of the weight dynamics provided statistically and clinically significant weight loss in both patient groups (p<0,001). When evaluating the dynamics of the eating behavior we established a statistically significant rise in the level of restraining eating behavior in the group of patients receiving pharmaceutical treatment (p<0,01). The same group of patients demonstrated a statistically relevant decrease in the level of emotional eating behavior (p<0,01). Evaluation of the dynamics of the level of hunger demonstrated a statistically relevant decrease in the group of patients receiving subitramine (p<0,01). Evaluation of the mediators of the energy metabolism demonstrated a statistically relevant decrease in leptin level in the 1st group (p<0,01) and a statistically relevant decrease in basal and stimulated insulin level in both groups (p<0,008). GH level didn’t demonstrate a statistically significant dynamics in any group of patients. Conclusion: The loss of weight caused by sibutramine intake resulted in the rise of level of restraining eating, decrease in the level of emotional and external eating behavior; decrease in leptin and insulin level.


HYPERCYTOKINEMIA: INCREASED OR DECREASED INNATE IMMUNITY‌
M. Watve^1,2, S. Mandani², P. Belsare^2
1)Anujeeva Biosciences Pvt. Ltd., Pune, India ²⁾Abasaheb Garware College, Pune, India

The adipose tissue is an active endocrine organ which secretes proinflammatory cytokines and chemokines resulting into raised serum levels. Hypercytokinemia has been interpreted as a raised level of innate immunity and its evolution is interpreted as a response to increased chances of infection under starvation conditions in which the thrifty phenotype evolved. If starvation and infection challenges co-occurred during hunter gatherer life, thrifty genotype and infection resistant genotype may have co-evolved. An inherent weakness of this explanation is that the raised levels of inflammatory cytokines have not been demonstrated to combat infections or enhance wound healing. We suggest that the raised chemokine levels actually decrease peripheral innate immunity. The normal movement of monocyte-macrophages and neutrophils from blood vessels to injured tissue is under a chemokine gradient. A gradient results from the difference between the basal levels of chemokines and those secreted by the injured tissue. Increase in the basal level is expected to weaken the gradient thereby decreasing extravasation and infiltration. Using diffusion kinetics we show that a small rise in basal levels can cause substantial reduction in cell infiltration. This interpretation is consistent with the behavioural switch hypothesis proposed by Watve and Yajnik which suggests that obesity and insulin resistance mark a transition from “soldier” to “diplomat” lifestyle. Hypercytokinemia may have evolved as a mechanism of disinvestment in peripheral innate immunity since the diplomat lifestyle is less injury prone. We evaluate the two alternative hypotheses with available evidence.


REDUCTION IN SYSTEMIC INFLAMMATION IN RESPONSE TO BEHAVIOURAL THERAPY
M. Watve^1,3, P. Belsare¹, C. Kumbhar³, P. Patil³, M. Jog^2
1)Department of Microbiology, Abasaheb Garware College, Pune, India ²⁾Department of Biotechnology, Abasaheb Garware College, Pune, India ³⁾Anujeeva Biosciences Pvt Ltd, Pune, India

An upcoming hypothesis for raised systemic levels of cytokines and inflammatory markers is that the immune system is retracted from the periphery in response to a non-injury-prone life style. In obesity and insulin resistance syndrome, the density of monocyte-macrophage and other immune cells in adipose tissue and blood circulation increases and that in peripheral tissues decreases. This is hypothesized as a form of immune redistribution in response to a transition from ‘soldier’ to ‘diplomat’ lifestyle. A testable prediction of the hypothesis is that behavioural components of ‘soldier’ lifestyle namely physical aggression, quick reflexes and injury-proneness should drive the immune system to periphery and reduce systemic inflammation. To test this hypothesis a group of 17 type 2 diabetic patient volunteers were given exercises involving physical aggression, quick reflexes and cutaneous immune-sensory stimulation (CISS) for 4 days under supervision and were advised to continue a given set of exercises later. The blood monocyte count showed significant decline in 4 days and total WBC, granulocyte and lymphocyte count as well as HbA1c significantly decreased in one month. CRP showed a decreasing trend but was not statistically significant, however there was a significant positive correlation between CRP and total WBC. Analysis of self reported compliances revealed that compliance with CISS was negatively correlated with change in total WBC count and total monocyte count. Compliance with aggression exercises was negatively correlated with change in blood granulocytes. These changes were not explained by total energy expenditure by these exercises alone.


EFFECTS IN DB/DB MICE OF PLANT EXTRACTS ACTIVATING PPAR- IN VITRO
S. Wein¹, E. Schrader^1,2, G. Rimbach², S. Wolffram^1
1)Institute of Animal Nutrition & Physiology, Christian-Albrechts-University of Kiel, Germany ²⁾Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Germany

Plants with potential anti-diabetic effects were identified by a literature survey. Plant extracts (four step sequential extraction procedures with n-hexane, dichloromethane, methanol, and water or single step extraction with ethyl acetate) were tested for selective peroxisome-proliferator-activated receptor (PPAR) transactivation. Extracts with highest PPAR- activation were: sambucus nigra (ethyl acetate extract of flowers), satureja montana and fagopyrum esculentum (dichloromethane extract of aerial parts) and echinacea pupurea (n-hexane extract of florets). These extracts were fed at a concentration of 0.01 and 0.1 % in the diet to 5-week old female db/db mice (BKS.Cg-m +/+ Leprdb/J). Rosiglitazone (PPAR- agonist, oral anti-diabetic drug) served as positive control while the negative control received non-supplemented flavonoid depleted maintenance chow and body weight was monitored weekly. After 4 weeks blood was sampled in the 12 h fasted state and serum parameters (glucose, triacylglycerol, free fatty acids (FFA), cholesterol) and selected hormones (insulin, adiponectin) were measured. Additionally wet weights of liver and fat pads were measured. Compared to each other group, Rosiglitazone led to higher body weight, plasma adiponectin concentrations, smaller fat pads, lower serum glucose and cholesterol concentrations. No changes were found concerning liver wet weight and serum FFA and triacylglycerol concentrations. Interstingly lowest plasma insulin concentrations were found in the group receiving dietary 0.01 % satureja montana extract. We conclude that under the condition of the present study the extracts did not exert PPAR--ligand activity. This, however, does not exclude that the selected plants may have anti-diabetic effects mediated by other pathways.


GENE EXPRESSION PROFILES INDUCED BY HIGH FAT DIETS IN RAT SKELETAL MUSCLE, WHITE ADIPOSE TISSUE AND LIVER
S. Wein¹, J. Schrezenmeir², K. Herzig³, S. Wolffram^1
1)Institute of Animal Nutrition and Physiology, University of Kiel, Ger ²⁾Department of Physiology And Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Centre for Nutrition and Food, Karlsruhe, Ger ³⁾A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Kuopio, Finland

Background & Objective: Euglycemic hyperinsulinemic clamp (EHC) studies revealed impaired insulin sensitivity (IS) after 4-week ad libitum feeding of high fat diets (56 energy %) from long chain fatty acids (LCSFA [C16:0, C18:0]), while IS in rats fed medium chain fatty acids (MCSFA [C8:0, C10:0]) did not differ from controls fed maintenance chow. Thus we compared the impact of isocaloric, isonitrogenic LCSFA and MCSFA -diets on gene expression profiles (GEP) in rats. Materials & Methods: Dietary effects of LCSFA, MCSFA and maintenance chow were monitored in 45 Wistar rats by measuring body weight gain, plasma concentrations of glucose, insulin, adiponectin, leptin, triacylglycerols and cholesterol as well as tissue triacylglycerols and fatty acids. Genome-wide expression profiles of skeletal muscle, adipose tissue and liver were performed using Affymetrix GeneChip technology (Rat Genome 230 2.0 Array) in 3 individual samples per tissue and group (MCSFA versus LCSFA) respectively. Differentially expressed genes were detected by two-sample, two-sided t-tests using probe sets with reliable signals. Genes with p value less than 0.05 were considered candidate genes. Results & Conclusions: Comparing the effects of MCSFA - versus LCSFA-intake, we found in epididymal adipose tissue 1113 genes up- and 1263 down-regulated, in liver 239 genes up- and 704 down-regulated and in skeletal muscle 326 genes up- and 457 genes down-regulated. Our GEP together with findings from EHC studies, plasma and tissue parameters give evidence to the versatile role of adipose tissue and do support the lipotoxicity theory in the context of the development of insulin resistance.


QUERCETIN ENHANCES INSULIN SENSITIVITY BY A PPAR- INDEPENDENT MECHANISM IN RATS FED A HIGH FAT DIET
S. Wein¹, N. Behm¹, E. Schrader^1,2, J. Tereszczuk¹
K. Kristiansen³, G. Rimbach², S. Wolffram^1
1)Institute of Animal Nutrition & Physiology, Christian-Albrechts-University of Kiel, Germany ²⁾Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Germany ³⁾Department of Biochemistry And Molecular Biology, University of Southern Denmark, Denmark

Objective: The present study investigated effects of the flavonol quercetin on insulin sensitivity, peroxisome-proliferator-activated-receptor (PPAR)- activation, adipokines and cytokines and on oxidative stress. Research Design and Method: Rats (n = 33) were fed a high-fat-diet with (HFQ) or without (HF) 0.03 % quercetin over 4 weeks. Another group was fed a low-fat maintenance diet (LF). Body weight was measured weekly, and serum concentrations of adiponectin, leptin, interleukins (IL-1, IL-6), tumor necrosis factor alpha, glucose, insulin, free fatty acids, triacylglycerols and total cholesterol were measured at the end of the feeding period. A reporter gene assay using co-transfected COS-1 cells was used to investigate PPAR- activation in vitro. Result: Quercetin did not affect body weight gain, relative organ weights and serum leptin levels. Quercetin, however, decreased the HOMA index in rats fed the HF diet to levels below that in LF animals. Plasma adiponectin concentrations were significantly elevated in the HFQ compared to the HF group whilst the level of PPAR- mRNA was decreased (HFQ vs. HF) by quercetin in muscle, liver and adipose tissue. Additionally, quercetin did not activate PPAR- in the cell culture study. Plasma concentration of 8-iso-PGF2 was 4 to 5 times lower in the HFQ group compared to both other groups. Conclusion: We conclude that the insulin-sensitizing effect of quercetin observed in the present study is independent of PPAR- activation and could be mediated by an enhanced adiponectin secretion. In addition, quercetin exerts a protective effect against lipid peroxidation associated with insulin resistance.


PULSE PRESSURE IS A MAJOR PREDICTOR OF MORTALITY IN ELDERLY PATIENTS
A. Weiss¹, M. Boaz², Y. Beloosesky¹, R. Kornowski¹, E. Grossman^3
1)Rabin Medical Center, Petach-Tikva, Israel ²⁾Wolfson Medical Center, Holon, Israel ³⁾The Chaim Sheba Medical Center, Tel-Hashomer And Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Background: Pulse pressure (PP) values increase with age. PP is a strong risk factor for cardiovascular pathologies; however, its impact on mortality in very elderly patients has not been studied. Objectives: To evaluate the effect of PP on mortality among elderly patients. Methods The medical records of 470 inpatients (226 males, mean age of 81.5±7 years) hospitalized in an acute geriatric ward between 1999 and 2000 were reviewed. Blood pressure values were measured three times during a day (in the morning, in the after noon and in the evening). Patients were followed-up until August 31, 2004. Mortality data were extracted from death certificates. Results: Age, male sex, diabetes mellitus, congestive heart failure and creatinine levels were positively associated and BMI and hemoglogin were inversely associated with all cause mortality. Systolic and diastolic blood pressure were not associated with all cause mortality; however, PP was significantly, positively associated with all cause mortality such that each 1 mmHg increase in PP was associated with a relative increase of 1.5% in risk of all cause mortality (95% CI 0.4-2.6%, p=0.009). This association persisted even after controlling for age, sex, BMI, hypertension, diabetes mellitus, congestive heart failure, smoking, creatinine and hemoglobin. Conclusion: PP emerged as a strong, independent predictor of mortality among elderly hospitalized patients. PP may represent a prognostic tool in this patient population.


DE NOVO LIPOGENESIS AND VLDL-TRIGLYCERIDE SATURATED FATTY ACID COMPOSITION IN NON-DIABETIC VERSUS DIABETIC SUBJECTS FOLLOWING LOWER FAT/HIGHER CARBOHYDRATE INTAKE
M. Wilke¹, M. French¹, Y. Goh¹, E. Ryan ², M. Clandinin^1,2
1)Alberta Institute for Human Nutrition ²⁾Department of Medicine, Canada

Objectives: Lowering saturated fat intake is recommended to diabetic patients to reduce CVD risk, but increasing carbohydrate intake may result in higher saturated fatty acids (FAs) in VLDL-triglyceride (TG). Isotopic methods were used to examine the contribution of hepatic de novo lipogenesis (DNL) to VLDL-TG FAs. We hypothesized that synthesis and composition of total and saturated FAs would be higher in diabetic subjects during lower fat/higher carbohydrate intake. Methods: Seven type 2 diabetic subjects were matched (age, gender, BMI) with 7 non-diabetic control subjects. Two diets differing in fat energy (LF<25%, HF>35%, difference mostly oleate) were consumed for 3d (blinded, randomized, crossover, 1-mo washout). Blood samples were drawn before and 24h after ingestion of deuterium-labeled water. Results: In control subjects HF intake resulted in lower total VLDL-TG FAs than the LF diet (2.0±1.4 vs 1.2±0.7 mmol/L) due to reductions in myristic, palmitic, palmitoleic and linoleic acids. The opposite trend was observed in diabetes subjects (1.6±1.0 vs 2.3±1.5 mmol/L). Fractional synthesis rate was reduced by HF compared to LF intake (control: 19±12% vs 14±9%, diabetes: 15±8% vs 12±9%, respectively) and ranged from 0-33% of VLDL-TG FA. Palmitate accounted for 68% of FAs synthesized. Conclusions: Deuterium incorporation techniques were used for the first time in humans showing variability in the synthesis rate of specific FAs. A LF diet increased synthesis of saturated FAs at high enough rates to contribute to VLDL-TG FAs. HF intake had a suppressive effect on DNL despite differences in VLDL-TG FA composition. Funding: Canadian Diabetes Association.


AMPK IS ACTIVATED BY THYROID HORMONE VIA ACTIVATION OF CAMKK-BETA
M. Yamauchi^{1, 2}, X. Cao¹, F. Kambe^1
1)Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan ²⁾Nagoya University School of Medicine, Nagoya, Japan

AMP-activated protein kinase (AMPK) is a key regulator of glucose and fatty acid homeostasis. AMPK stimulates mitochondrial fatty acid oxidation and ATP production in muscle cells. The thyroid hormone T3 increases cellular oxygen consumption, and is a major regulator of mitochondrial activities. In this basic study, we examined the possible involvement of AMPK in the stimulatory action of T3 on mitochondria. Treatment of C2C12 myoblasts with T3 rapidly led to phosphorylation of AMPK. Acetyl-CoA carboxylase, a direct target of AMPK, was also phosphorylated following T3 treatment. Similar results were obtained with 3T3-L1, FRTL-5 and HeLa cells. Because HeLa cells express only Ca2+/calmodulin-dependent protein kinase kinase-beta (CaMKK-beta), one of two known AMPK kinases, it was suggested that the effect of T3 is mediated by CaMKK-beta. Indeed, experiments using a CaMKK inhibitor, STO-609, and an isoform-specific small interfering RNA demonstrated the CaMKK-beta-dependent phosphorylation of AMPK. Furthermore, T3 rapidly induced intracellular Ca2+ mobilization in HeLa cells, and a Ca2+-chelator, BAPTA, suppressed T3-dependent phosphorylation of AMPK. In addition, T3-dependent oxidation of palmitic acids was attenuated by BAPTA, STO-609 and the small interfering RNA for CaMKK-beta. These results demonstrate that T3 non-transcriptionally activates AMPK via intracellular Ca2+ mobilization and CaMKK-beta activation, thereby stimulating mitochondrial fatty acid oxidation.


EFFECTS OF AIR POLLUTION ON BLOOD PRESSURE, APOLIPOPROTEIN B, AND HBA1C IN CHINESE POPULATION WITH METABOLIC SYNDROME
Y. Yan^1,2, K. Chuang^1,3, C. Lu², T. Chen⁴, H. Wang⁴, T. Cheng^1
1)Institute of Occupational Medicine And Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan. ²⁾Division of Endocrinolgy And Metabolism, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan. ³⁾Department of Cosmetic Application and Management, St. Mary’S Medicine Nursing and Management College, Yilan, Taiwan ⁴⁾Bureau of Health Promotion, Department of Health, R.O.C. Taichung, Taiwan

Background- The association of air pollution with cardiovascular morbidity and mortality is well documented. The susceptibility of people with metabolic syndrome (MS) to air pollution is still unclear. Methods and Results- We conducted secondary analyses of blood markers, blood pressure and MS data from Taiwanese Survey on Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension (TwSHHH) and air pollution data from the Taiwan Environmental Protection Administration. Associations of 1-day to 6-day averaged criteria air pollutants {particulate matter with aerodynamic diameter < 10 ìm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)} with hemoglobin A1c (HbA1c), apolipoprotein B (ApoB), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were explored by applying generalized additive models. After controlling for potential confounders and MS components, we observed the association between increased 1-day averaged particulate matter with aerodynamic diameter < 10 ìm (PM10) and SBP, and associations of increased 3-day averaged PM10 with ApoB and HbA1c. Elevation in 3-day averaged ozone (O3) was associated with increased DBP, ApoB and HbA1c. We also found that people with MS showed higher response to increased levels of PM10 and O3 than those without MS. Conclusions- Exposure to PM10 and O3 are associated with increased HbA1c, ApoB and blood pressure. People with MS may be a more susceptible population.


A NOVEL COMPOUND G25BT2 IMPROVES GLUCOSE HOMEOSTASIS IN DIABETIC RATS BY REVERSING ALTERED EXPRESSION, ACTIVITIES OF CARBOHYDRATE METABOLIC ENZYMES AND GLUT4 DISTRIBUTION
M. Yanda, P. Anand, V. Tandon, M. P.S, R. Chandra
Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India

A precise balance between glucose production and its use maintains glucose homeostasis where key enzymes of glycolysis and gluconeogenesis play a crucial role along with the tissue glycogen content. An alkaloidal fraction (G25BT2) isolated from aqueous extract of the fruits of Terminalia chebula Retz. (AETC) has been evaluated for its antidiabetic activity in streptozotocin induced diabetic rats. In this study we have investigated the long term effect of G25BT2 on the activity and expression of key regulatory enzymes of carbohydrate metabolism and the effect on GLUT4 distribution in skeletal muscle tissue. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities and expression of gluconeogenic enzymes were higher in both liver and kidney during diabetes. After treatment with G25BT2 for two months the altered enzyme activities were significantly restored to near to control values in both the liver and kidney tissues, also corrected the alterations in the distribution of GLUT4 in the skeletal muscle. These findings suggest further investigations for the possible use of the fraction G25BT2 isolated from aqueous extract of the fruits of T.chebula for the therapy of diabetes.


AETC IMPROVES GLUCOSE HOMEOSTASIS IN DIABETIC RATS BY REVERSING ALTERED ENZYMES AND GLUT4 DISTRIBUTION.
M. Yanda, P. Anand, V. Tandon, R. Chandra
Dr. B. R. Ambedkar Center for Biomedical Research, Delhi University, Delhi-110007, India

Background and aims: A precise balance between glucose production and its use maintains glucose homeostasis where key enzymes of glycolysis and gluconeogenesis play a crucial role along with the tissue glycogen content. The aqueous extract of the fruits of Terminalia chebula Retz. (AETC) has been evaluated for its antidiabetic activity in streptozotocin induced diabetic rats .Methods: In this study we have investigated the long term effect of AETC on the activity and expression of key regulatory enzymes of carbohydrate metabolism and the effect on GLUT4 distribution in skeletal muscle tissue. Results: The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities and expression of gluconeogenic enzymes were higher in both liver and kidney during diabetes. After treatment with AETC for two months the altered enzyme activities were significantly restored to near to control values in both the liver and kidney tissues, also corrected the alterations in the distribution of GLUT4 in the skeletal muscle. Conclusions: These findings suggest further investigations for the possible use of the aqueous extract of the fruits of T.chebula for the therapy of diabetes.


EVALUATION OF ORTHOSTATIC BLOOD PRESSURE CHANGES IN HYPERTENSIVE PATIENTS WITH OVERT DIABETIC NEPHROPATHY USING ABPM EQUIPPED WITH A POSITION-SENSOR
G. Yasuda, C. Kobayashi, M. Kobayashi, T. Kaneda, T. Yoshida, D. Ando, K. Yatsu, N. Hirawa, S. Umemura
Yokohama City University Center Hospital, Japan

Objectives: Autonomic nervous dysfunction is often seen in diabetic patients and readily induces a drop in blood pressure (BP), when they assume an upright position. We analyzed standing and sitting BP obtained from diabetic patients using ambulatory BP monitoring equipped with a position-sensor. Power spectral analysis of the heart rate was also performed for the high frequency (HF) and low frequency (LF) components, as an index of the sympathovagal balance. Methods: Diabetic patients were divided into two groups on the basis of renal function: diabetic group (D group; serum creatinine level <1.5 mg/dL; men/women, 15/22; mean age, 64±9 years) and renal failure group (R group; serum creatinine level 1.5-3 mg/dL; men/women, 26/16; mean age, 64±11 years). Non-diabetic patients with hypertension (EH group; serum creatinine level <1.5 mg/dL; men/women, 25/28; mean age, 59±16 years) were also examined. Results: Mean standing BP was 159±18 (SD)/87±12 mmHg in D group, which were as high as 158±25/84±14 mmHg in R group but was higher (p<0.05) than 152±21/84±12 mmHg in EH group. There were no differences (p>0.05) in mean sitting BP between D group (156±19/85±12 mmHg) and R group (156±23/83±13 mmHg) but they were higher (p<0.05) than 151±20/82±12 mmHg in EH group. The absolute change in systolic BP detected during 5-minute after standing was 4.6±18.1 mmHg in D group, which was as high as 2.5±16.1 mmHg in EH group but was higher (p<0.05) than -0.2±18.0 mmHg in R group. Both HF and LF components did not differ between D group (13.3±9.0 and 20.7±10.6) and R group (14.8±11.0 and 19.4±10.6) but were lower (p<0.05) than those (19.1±11.8 and 34.5±16.9) in EH group. Conclusion: These findings suggest that orthostatic hypotension did not develop in D group although the sympathovagal balance was damaged in the early stage of renal impairment.


CORRELATION BETWEEN COMPONENT OF METABOLIC SYNDROME AND MGP/BMP4 RATIO INDUCED BY PROINFLAMMATORY CYTOKINES AMONG ADULT MEN
T. Yulianti, A. Wijaya, M. Arief
Hasanuddin University Indonesia

Objective. Metabolic syndrome (MetS) is an inflammatory state that associated with the risk for atherosclerosis and more than 90% of atherosclerotic plaque calcification undergo calcification. The aim of this study was to observed the correlation between matrix gla protein (MGP), bone morphogenic protein 4 (BMP-4) as vascular calcification regulator, metabolic syndrome components and high sensitive C reactive protein (hsCRP) .Methods. The study was observational with a cross sectional design. We defined MetS by the International Diabetes Foundation 2005 criteria among 80 male subject aged 30-60 years. Concentration of BMP4, MGP, and hsCRP were measured by EIA method. To determine correlation between MGP/BMP4 ratio and the number of MetS component, we devided participant into groups by IDF criteria due to correlation analysis. Results. Out of 80 subjects, 47 and 33 were classified as MetS and non MetS groups, respectively. The mean age was 44 years. The mean concentration of MGP, BMP4 and hsCRP successively were 8.295 nmol/L, 529.854 pg/mL, and 2.36 mg/L. There was a linier correlation between MGP and log-hsCRP (r=0,367; p=0,018), BMP4 and log-hsCRP (r=-0,277; p=0,03), BMP4 and number of metabolic syndromes components (r=0.232; p=0,03), MGP/BMP4 ratio and log-hsCRP (r=0,293; p=0,008), MGP/BMP4 ratio and number of metabolic syndrome components (r=0,266; p=0,017). The ratio of MGP/BMP4 was higher in MetS than non Mets (p= 0,014). Conclusion. MetS and proinflammatory cytokines are strongly associated with higher MGP/BMP4 ratio.


HEART RATE VARIABILITY IN OBESE SUBJECTS DURING TILT TABLE TEST
P. Zalewski¹, K. Buszko², J. Klawe³, M. Tafil-Klawe⁴, P. Weber^4
1)Department of Lasertherapy and Physiotherapy ²⁾Department of Theoretical Foundations of Biomedical Sciences ³⁾Department of Hygiene and Epidemiology ⁴⁾Department of Physiology, Poland

Heart rate variability contains information about the status of the autonomic nervous system. The Low frequency component (LF-RR) seems predominantly due to sympathetic discharge acting on the cardiac on the cardiac frequency variability. The High-frequency component (HF-RR) is predominantly due to vagal activity. The power of the LF- and HF-components together with their ratio (LF/HF) are quantitative indices to the sympatho-vagal balance. The aim of the study was the estimation of cardiovascular autonomic regulation among obese subjects, in order to test the hypothesis, that dysfunction of the autonomic nervous system plays the main role in pathogenesis of cardiovascular diseases in obesity. Ten obese subjects (BMI 35,4) and ten subjects with normal body weight (BMI 23,4) were involved in the study. Heart rate variability was analyzed during tilt test, where “I” means a supine and “II” – an upright posture. In our study we observed domination of sympathetic component of the autonomic system activity in obese subjects, in comparison to the control group. We conclude, that increase in sympathetic activity in obesity might provide to the disturbances of cardiovascular control and tendency toward dominance of sympathetic system. Results (control subjects / obese subjects): LF-RR I 1615,8 / 702,8 LF-RR II 1365,7 / 516,4 HF-RR I 1492,5 / 414,5 HF-RR II 1218,3 / 328,6 LF/HF-RR I 1,20 / 2,05 LF/HF –RR II 1,47 / 2,67


OBESITY, WHR, AND FOOD HABITS OF MI PATIENT IN SHAHID MADANI HEART HOSPITAL TABRIZ- IRAN
F. Zargari¹, F. Zargari², N. Rahnomaye Hayati^1
1)Emam Reza Educational, Treatment & Research Center, Tabriz ²⁾Marand Azad University East Azarbaijan, Iran

Introduction: Obesity is one of the health problems in the world. It is associated with some risk factors such as diabetes, hypertension, atherosclerosis. This study determines types of obesity, fat distribution and some of food habits in MI patients. Metods :About 126 MI patients (70 males, 56 females) were selected... Socioeconomic and food habits questionnaires were completed. Body mass index and WHR was measured. (BMI >30 for obesity, WHR > 0/8, and > 0/95 for central obesity for women and men respectively(. Results: 53% of males and 57% of females had central obesity. 6% of males and 42% of females were obese ( BMI>30) . Their food habits were as follows : Consumption of animal oil ( 89%) Consumption of maet and egg (26.1% and 11.4%) Consumption of fish occationally ( 14.5%) Consumption of beans monthly (82%) Consumption of milk (31%) Conclusion : prevalence of obesity and central obesity was high in females with MI , so increasing of nutritional knowledge and guidance on weight control sterategies in MI patients is needed.


EFFECT OF PPARδ AGONIST ON CERAMIDE METABOLISM IN RAT SKELETAL MUSCLES
M. Zendzian-Piotrowska, J. Gorski, T. Kononczuk
Medical University of Bialystok, Department of Physiology, Poland

Peroxisome proliferator activated receptor (PPAR) δ is involved in regulation of lipid metabolism in different tissues. However, there are no data on its involvement in regulation of sphingolipid metabolism and it was the aim of the present study to examine this problem in skeletal muscles. The experiments were carried out on male Wistar rats. The animals were divided into two groups: 1) fed with a standard diet for rodents, 2) fed with high fat diet for 5 weeks. Each group was divided into two subgroups: 1-control, 2-treated with GW-0742, the PPARä agonist. Samples of the muscles (the white and red section of the gastrocnemius, the soleus). Sphingomyelin was isolated by means of thin layer chromatography and its fatty acid residues were analyzed using of gas-liquid chromatography. The content of ceramide, sphingosine, sphinganine and sphingosine-1-phosphate was measured by high-pressure liquid chromatography. The activity of neutral ceramidase and sphingomyelinase was determined with the use of radiolabelled substrates. It was found that stimulation of PPARä increased the level of sphingomyelin and reduced the activity of neutral sphingomyelinase in the soleus and red gastrocnemius muscle. It did not affect the content of ceramide in the examined muscles. Treatment with GW0742 increased the level of sphinganine, sphingosine-1-phosphate, sphingosine and the activity of neutral ceramidase in these muscles. PPARä activator didn’t affect the level/ activity of the examined variables in the white gastrocnemius in either group. It is concluded that stimulation of PPARä has profound effect on the metabolism of ceramide in the oxidative muscles.


NO EVIDENCE FOR INCREASED EXPRESSION OF RENIN-ANGIOTENSIN SYSTEM AND PROTEIN OXIDATION IN ADIPOSE TISSUE OF ADULT OBESE ZUCKER RATS
S. Zorad¹, R. Fiala¹, P. Grancic², M. Kukan², M. Baculikova^1
1)Institute of Experimental Endocrinology SAS, Bratislava, Slovakia ²⁾Slovak Medical University, Bratislava, Slovakia
We hypothesized that angiotensin II (Ang II), considered as growth factor, might contribute to development of hypertrophic obesity. In order to check the hypothesis we studied the expression of components of renin-angiotensin system (RAS) and protein oxidation in adipose tissue of 3-month-old obese Zucker rats. Serum glucose was determined using auto-analyzer Hitachi 911. Serum hormone levels were evaluated by radioimmunoassay. Gene expression was assessed by real-time PCR. Protein oxidation was measured using OxyBlot Protein Detection Kit. Adult obese Zucker rats were hyperglycemic, hyperinsulinemic, hyperleptinemic with increased serum levels of adiponectin. They had also elevated serum levels of cholesterol, free fatty acids, triglycerides and impaired bile secretion in liver. Surprisingly, we found decreased angiotensinogen, angiotensin-converting enzyme, AT1 receptor gene expression in epididymal adipose tissue of obese rats. AT2 receptor gene expression was not changed. Protein oxidation in adipose tissue was also not changed in obese animals. The lack of protein oxidation is in accordance with reduced local RAS and published data on reduced lipid oxidation in adipose tissue of obese rats. We believe that our data are in support of defense mechanism against obesity present in adipose tissue of 3-month-old obese Zucker rats. A part of this mechanism might be the elevated serum level of adiponectin. Research relating to this abstract was funded by Grant VEGA 2/0162/08 and by Grant APVV 21-010805.


CHANGES IN ADIPOSE TISSUE IN PATIENTS WITH DIFFERENT FUNCTIONAL CLASSES OF CHRONIC HEART FAILURE (CHF)
G. Arutyunov¹, K. Rogov², C. Shavgulidze¹, N. Bylova^1
1)Russian State Medical University, Moscow, Russia ²⁾Citi Clinical Hospital #4, Moscow, Russia

CHF - outcome of different cardiac diseases. Cardiac cachexia - body wasting is a serious complication of CHF especially in patients with diabetes mellitus long known but little investigated. It is associated with poor prognosis. Aim of study: to investigate visceral and subcutaneous fatty tissue in post-mortem examination of patients died due to CHF. Methods: in this trail we include 17 cases of deaths due to CHF: 4 – CHF I FC NYHA, 3 – CHF II FC NYHA, 6 – CHF III FC NYHA, 4 – CHF IV FC NYHA. Appraisal of FC of CHF performed before patient died. We perform measurement of thickness of subcutaneous fatty tissue and weight of omental and histology investigation of visceral and subcutaneous fatty tissue (hematoxylin and eosin stain .Results: thickness of subcutaneous fatty tissue was: I FC - 2.9±1.69 sm, II FC - 3,6±0,53 sm, III FC - 3,05±0,75 sm, IV FC - 1,35±1,1 sm. Weight of omental: I FC - 358±214.8 g, II FC - 511±62,7 g, III FC - 319,7±176,0 g, IV FC - 84,5±76,9 g. By histology investigation we find out, that in high classes of CHF adiposities were smaller, then in I-II FC of CHF. Also, in III-IV FC of CHF there were more collagen in adipose tissue and lymphocyte infiltration as a marker of chronic inflammation. Maximum of histology changes were find in visceral adipose tissue. Conclusions: in high classes of CHF we find changes in amount and morphology of adipose tissue, which were worst in visceral adipose tissue.


LONG-TERM OF HIGH-UNSATURATED FATTY ACID DIET-INDUCED OBESITY NOT ALTERED CARDIAC LIPOTOXICITY AND FUNCTION
A. Nascimento, R. Luvizotto, D. Campos, A.P. Lima-Leopoldo, M. Sugizaki, A. Leopoldo, F. Seiva, L. Justulin Jr , S. Fabio, K. Okoshi, A. Cicogna
Department of Medicine Clinical, Botucatu School of Medicine, Sao Paulo State University (UNESP) SP - Brazil

Background: Obesity has been associated with cardiac lipotoxicity and dysfunction. Short-term of high- unsaturated fatty acid diet might prevent cardiac dysfunction by inibithion of cardiac lipid accumulation. At present, there is little information regarding the more long-term effects of unsaturated fatty acid diet on the heart in the presence of obesity. Thus, the objective this study was evaluate the influence of prolonged high-unsaturated fatty acid diet-induced obesity on the cardiac lipotoxicity and function. Experimental design: Male Wistar rats (150g) were housed in individual cages and randomly divided into four groups: control diet (3.16 Kcal/g) and high-unsaturated fatty acid diet (4.08 Kcal/g) for 15 (C15 and UFA15, respectively) and 45 (C45 and UFA45, respectively) consecutive weeks. The obesity was defined as increased of adiposity index (fat depots normalized by body weight). Cardiac morphologic and function was evaluated by Doppler ecocardiographic. Lipotoxicity on heart was analized by cardiac triglyceride and lipid hydroperoxide accumulation. A two-way ANOVA was used to compare data among groups. Results: The high-unsaturated fatty acid diet for 15 and 45 consecutive weeks promoted obesity in animals characterized by increased adiposity index in associate with increased body weight, but was not associated with co-morbidities as hyperglycaemia, hypertriglyceride and elevated arterial pressure. There was no difference in cardiac morphological and functional parameters. Cardiac triglyceride and lipid hydroperoxide, a marker of cardiac lipotoxicity, was similar among treatment groups. Conclusion: Long-term of high-unsaturated fatty acid diet not occasioned cardiac lipotoxicity and dysfunction, despite in the presence of obesity.
CNPq: 471256/2007-2


PLASMA LEVELS OF ADIPOKINES DO NOT FOLLOW THE TIME-COURSE OF INSULIN SENSITIVITY DURING A 6 MONTHS´ WEIGHT REDUCTION
V. Stich¹, E. Klimcakova¹, M. Kovacikova¹, Z. Kovacova¹, J. Hanacek², J. Polak¹, D. Langin³, M. Vitkova^1
1)Third Faculty Of Medicine, Prague, Czech Republic ²⁾Institute For Mother And Child Care, Prague, Czech Republic ³⁾Inserm, U586, Unité De Recherches Sur Les Obésités, Toulouse , F-31432 France

Background: Adipocytokines produced by adipose tissue are suggested to play a role in the development of insulin resistance. Aim: To investigate,during the diet-induced weight reduction, the relationship between the changes in insulin sensitivity and the time-course of plasma adipocytokines supposedly involved in the development of insulin resistance Methods: 21 obese women (body weight 95.3±14.7kg) were investigated at basal conditions, after a 4 weeks´ very low calorie diet (VLCD) (800kcal/day), subsequent 8 weeks´ low calorie diet (LCD)(1200kcal/day) and subsequent 12 weeks´ weight maintenance (WM) phase. At each stage, plasma samples were obtained and insulin resistance was assessed using euglycemic hyperinsulinemic clamp. Plasma samples were analyzed using Luminex multiassay method. Results: The weight loss was 7.2±1.5 kg and 10.0±3,9kg after VLCD and at WM, respectively. Glucose disposal during the clamp increased by 35% after VLCD and 56% at WM compared to the basal state. Plasma levels of interleukins -6, -10 and -1-beta did not show any significant changes throughout the weight reduction program while interleukin-8 and tumor necrosis factor-alpha increased after VLCD and decreased to baseline levels thereafter. No correlations between the diet-induced changes of adipokines in relation to body weight or insulin sensitivity were found. Conclusion: Differencies in the time-course of plasma levels of adipocytokines in relation to that of insulin sensitivity do not support the hypothesis on the role of adipocytokines in the weight-reduction-induced changes of insulin sensitivity. The study was supported by grants GACR 04/0158 and IGA NR 9161-3-2007 and EU-supported programs HEPADIP and ADAPT.


VASCULAR FACTORS IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE
J. Lee¹, J. Kim¹, C. Chung^2
1)Dept. of Neurology, Asan Medical Center, Univ. of Ulsan College of Medicine ²⁾Dept. of Psychiatry, Asan Medical Center, Univ. of Ulsan College of Medicine, South Korea

Background & Objective: Vascular factors have been shown to be implicated not only in the development of vascular dementia, but also in the pathogenesis of Alzheimer’s disease. Mild cognitive impairment (MCI) is being considered as the precursor state of Alzheimer’s disease. A significant portion of the MCI population advances into Alzheimer’s disease over the years. The purpose of this study is to investigate whether there is a difference in vascular risk factors between MCI and Alzheimer’s disease using a hospital-based epidemiological study database. Methods: Petersen’s criteria and NINCDS-ADRDA criteria were used to define MCI and Alzheimer’s disease, respectively. All subjects underwent a brain MRI. Subjects who had a significant ischemic vascular change on MRI were excluded. Demographic data including vascular risk factors were entered in the web-based database registry. Results: Patients with Alzheimer’s disease were older than those with MCI (72.9 years vs. 69.2 years, p<0.005). Hypertension was more frequent in the MCI group (46.8%) than in the Alzheimer’s disease group (38.3%). The same is true for diabetes mellitus and hyperlipidemia (22.0% vs. 18.1% for diabetes; 16.9% vs. 11.8% for hyperlipidemia). On the other hand, heart disease, smoking, and body mass index were not different between the two groups. Conclusion: Despite younger age, patients with MCI had a higher frequency of vascular risk factors. These findings suggest that, considering MCI as a precursor to Alzheimer's disease, vascular risk factors such as hypertension, diabetes and hyperlipidemia may be implicated earlier on in the course of Alzheimer’s disease.


CIRCULATION FREE LEPTIN IN DIABETIC PATIENTS AND ITS CORRELATION TO INSULIN LEVEL
J. Mohiti-Ardekani, F. Talebi, M. Afghami
Yazd University of Medical Science, Yazd, Iran

Introduction. We studied free and total leptin. in obese and non-obese diabetic patients and their correlation to Insulin and Insulin resistant. Methods: Thirty non insulin dependent diabetic (NIDDM) obese patients (age: 54±12 yr & BMI>30 kg/m²) and Thirty non insulin dependent diabetic (NIDDM) non obese patients (age: 49±25 yr & BMI<25 kg/m²) were studied. . Free leptin was purified by Gel filtration chromatography and the fractions were collected and then their free leptin was measured by a high sensitive ELISA method. Circulation total leptin and insulin were measured by ELISA. Results: Mean levels of total and free leptin form in obese diabetes patients were 17.84 ±9 and 5.59 ± 4 (ng/ml) respectively, whereas these concentration were 2.3±1 and 0.12 ± 0.1 ng/ml in non-obese patients. The insulin level and Insulin resistant were greater in obese than non-obese (21.85±7 (Iu/ml) and 7.08 ±4 vs 10.12± 4(ng/ml) and 4.59 ±3 respectively. The cholesterol, HDL and LDL were greater in obese patient than non-obese patients respectively.Free leptin showed a positive correlation with insulin and BMI in obese and non-obese diabetes patients. (P<0.05(. Conclusion: The majority of leptin which circulates in obese individuals was free form. Presumably it is bioactive portion of hormone and thus obese subjects are resistant to free leptin. These observations are consistent with the view that free leptin levels in diabetes patients attributed to changes in serum insulin level and insulin resistant.


THE ABILITY OF HYPERTENSIVE WAIST TO PREDICT CARDIOVASCULAR RISK
C. Nita, A. Rusu, C. Bala, N. Hancu
"Iuliu Hatieganu" University of Medicine, Cluj Napoca, Romania

Background and Objective: In the previous studies we have suggested that hypertensive waist (HTW) is a frequent pathogenetic combination in persons with metabolic syndrome (MetS). The objective of this study was to compare the ability of metabolic syndrome and hypertensive waist to predict moderate and high cardiovascular risk (RCV). Study subjects and methods: The clinical and anthropometric data as well as the laboratory parameters had been analyzed from 1294 persons randomly selected from the general population. The HTW was defined as waist circumference ¡Ý 94 cm in men/ ¡Ý 80 cm in women and BP ¡Ý130/80 mm Hg. Metabolic syndrome was defined according to IDF criteria. Cardiovascular risk was assessed using the Framingham risk chart. Receiver operating characteristics (ROC) was used to compare the the performances of HTW and MetS. Results: The prevalence of hypertensive waist was 43.3% and the prevalence of the metabolic syndrome was 45.7%. 40.1% of patients with HTW had a CVR >20%. In patients with MetS, 31.62% presented a CVR >20%. For predicting moderate and high CV risk, HTW had a sensitivity of 62.9% and a specificity 67.1%;while, MetS had a sensitivity of 59.3% and a specificity of 61.4%. Also, the area under the ROC curve was slightly higher for HTW than for the MetS (0,650 vs. 0,603). Conclusion: HTW should be used as starting point to screen for moderate and high cardiovascular risk.


THE NATURAL PPAR LIGAND CLA CAUSES GENOMIC AND NON-GENOMIC EFFECTS IN LEUKOCYTES OF PATIENTS WITH METABOLIC SYNDROME
L. Mainwaring¹, H. Bolusani², M. Evans², R. Webb¹, K. Morris^1
1)Centre for Biomedical Sciences, University of Wales Institute Cardiff, Cardiff CF5 2YB ²⁾Llandough Hospital, Cardiff and Vale Nhs Trust, Cardiff Cf64 2XX

We have reported that, as well as exerting effects genomically via upregulation of PPAR£^ target genes, synthetic PPAR£^-ligands (eg. Rosiglitazone) can act via non-genomic mechanisms, where ligand-activated PPAR£^ receptors (or possibly ligands acting independently) modulate pre-existing signalling pathways. As concerns have been raised regarding increased risk of death from cardiovascular causes in Rosiglitazone-treated subjects means of inducing beneficial PPARƒ×-ligand-induced effects without causing deleterious effects are urgently required. The current study investigated whether conjugated linoleic acid (CLA), a natural PPAR£^-ligand, exerts similar effects to Rosiglitazone.40 patients with metabolic syndrome were recruited for dietary supplementation with CLA (2mg/day; 12weeks). Leukocyte mRNA expression (relative to GAPDH) of PPAR£^, the PPAR£^ target gene CD36, and the advanced glycation end-product receptor (AGER, whose expression is controlled by a different transcription factor, NF-kB) were assessed via RT-PCR. CLA supplementation brought about increases in PPAR£^ and CD36 expression (2.90¡Ó0.28 and 2.58¡Ó0.61 baseline respectively), suggesting that CLA is acting as a PPAR£^-ligand in this instance. Interestingly, AGER was also upregulated by CLA supplementation (2.50¡Ó0.41 baseline). Alternatively-spliced AGER isoforms include a gene product lacking a transmembrane domain (sAGER), which is secreted into the plasma, and so prevents glycosylated proteins from reaching leukocytes and subsequently triggering pro-atherogenic effects. On CLA supplementation, plasma sAGER levels (as measured using ELISA) increased from 874.4¡Ó61.4pg/ml at baseline to 1187.0¡Ó110.4pg/ml. As AGER is not a PPAR£^ target gene, this appears to be a non-genomic effect. Thus, the current study suggests that, like synthetic PPAR£^-ligands, CLA may exert effects via both genomic and non-genomic mechanisms.


ROSIGLITAZONE INDUCES ER STRESS RESPONSES, BUT NOT APOPTOSIS, IN MONOCYTES AND VASCULAR SMOOTH MUSCLE CELLS
J. Caddy¹, A. Thomas¹, A. Roberts², D. Lang³, R. Webb^1
1)Centre For Biomedical Sciences, University of Wales Institute Cardiff, Cardiff CF5 2YB ²⁾School of Medicine, University Hospital of Wales, Cardiff University, Cardiff CF14 4XN, UK ³⁾Wales Heart Research Institute, Cardiff University, Cardiff CF14 4XN, UK

Rosiglitazone, an insulin-sensitizing drug, is known to exert anti-hyperglycaemic effects. These are acheived via activation of the nuclear-receptor PPARgamma, and subsequent expression of PPARgamma-response-element (PPRE)-bearing target genes involved in the metabolism. However, safety concerns have recently been raised regarding the increased risk of myocardial infarction, and death from cardiovascular causes, in Rosiglitazone-treated subjects. We have previously shown that, in addition to activation of PPRE-bearing target genes in monocytes, non-cytotoxic concentrations of Rosiglitazone (1-20uM) cause PPARgamma-independent inhibition of the ER Ca2+-ATPase SERCA2b, leading to disrupted Ca2+ homeostasis. Here, we report that the consequences of extended Rosiglitazone treatment (10uM; 72hr) include activation of the ER stress-response transcription factor XBP-1, upregulation of SERCA2b, and ultimately restoration of Ca2+ homeostasis in both monocytes and.vascular smooth muscle cells. Thus, we propose that Rosiglitazone induces ER stress-responses. However, as an ER-stress-responsive gene, SERCA2b aids in restoring normal cell physiology, and ensures that Rosiglitazone does not induce apoptosis in this case. Finally, we studied vascular reactivity in denuded aortic rings from New Zealand White rabbits. Extended treatment with Rosiglitazone (10uM; 24hrs) induced increased sensitivity to the nitric oxide donor sodium nitroprusside (EC50 = 30.9±10.6nM; cf. EC50 = 39.8±7.4nM (control)), suggesting that Rosiglitazone could also play a vasorelaxatory role by improving vascular function - possibly via SERCA2b upregulation, and thence enhanced sensitivity to NO. As disrupted cellular Ca2+ homeostasis may be linked to hypertension and other diabetic complications, and may also be the mechanism behind Rosiglitazone’s association with negative cardiovascular events, this data may be of clinical significance.