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About Shanghai
The 1st Asia Pacific Congress on
Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy)
Shanghai, China, June 2-5, 2011
 
  Diabetes Therapy Print

IMPACT OF ANTI-DIABETIC MEDICATION ON THE CARDIOVASCULAR AND RENAL OUTCOME IN PATIENTS WITH DIABETES MELLITUS

J. Al Wakeel (1), D. Hammad (1), A. Mitwalli (1), A. Al Habi (2), M. Al Ghonaim (1) A. Al Suwaida (1)

1 King Saud University, Riyadh, Saudi Arabia

2 Security Forces Hospital University, Riyadh, Saudi Arabia

 

Background: Concerns have been raised that anti-diabetic agents may themselves increase the risk of cardiovascular and renal events in type 2 diabetic patients.

Objective: To investigate impact of anti-diabetic treatment by oral hypoglycemic (OH) agents alone and combined treatment with insulin and OH agents where Insulin was added after OH agents alone failed to control hyperglycemia on cardiovascular and renal outcome in type 2 diabetic patients.

Method: Retrospective study performed on 1952 diabetic patients in Security Forces Hospital, facilitated by King Saud University, Riyadh, Saudi Arabia from January 1989 to December 2004. Data included patients demographics, co-morbidities, clinical and laboratory data, cardiovascular, renal outcome and mortality.

Results: Total 1952 diabetic patients, 1073 on OH agents, 775 on combine therapy of OH agents and insulin. Comparing baseline characteristics of OH group vs. insulin and OH together. Age was 58.3±14vs.59.6±13.7 years, male sex 60.4%vs.43.4% (p=00). Duration of diabetes was 8.7±6.7vs.12.9±7.6 years (p=0.00), initial FBS was 9.6±2.4mmol/Lvs.9.7±2.4mmol/L. Initial serum creatinine was 72±35vs.74±35mmol/L. SBP was 132.3±19vs.131.9±19mmHg while DBP was 78.2±10vs.77.9±10mmHg. At last visit SBP was 128.4±20vs.129±21mmHg p=0.29, DBP was 78±8vs.76±9 mmHg, doubling serum creatinine was 8.1%vs.19.1% patients (p=0.00), uncontrolled hypertension was found in 18%vs.21.2% patients (p=0.08).GFR <60 ml.min at last visit was 22.3%vs.33.9% patients. DN was 19.3% vs. 35.2% patients. Increased need of dialysis was 2.2%vs.6.3% patients (p=0.00), greater incidence of MI 11.6%vs.18.6% (p=0.00), stroke 7.8%vs.14.3% (p0.00), foot infections 2.3%vs.7.2% (p=0.00) and mortality 7.5%vs.9.5% (p=0.13) was observed in OH plus insulin treated group.

Conclusion: Addition of insulin late when OH agents failed to control hyperglycemia has no benefit, rather risk of adverse renal and cardiovascular events and mortality increases in diabetic patients.

 

THE LUNG AS AN ALTERNATIVE ROUTE OF INSULIN DELIVERY

S. Alsayed (1)

1 New Jeddah Clinic Hospital, Jeddah, KSA

 

We examine the lung as an alternative route of delivery of insulin in controlling postprandial glucose level in 10 patients with type 2 diabetes mellitus. It is a Single-blinded, nonrandomized, placebo-controlled pilot study consisting of two visits. On the first day visit, we normalized fasting blood glucose levels by given 1 u of insulin aerosol into the lungs. Then, patients inhaled 1.5 U/kg insulin by aerosol into the lungs five minutes before ingesting a test meal. On the second day visit after two weeks the patients inhaled placebo aerosol during a morning fasting state in the same way as they had previously inhaled insulin aerosol. On both visits, plasma samples were collected and analyzed for glucose levels for 3 h during the postprandial state.

Results: No one coughed after inhalation of insulin aerosol or demonstrated hypoglycemia. During the postprandial period, glucose levels were significantly lower at 20 min), 1 h, 2 and 3 h mmol/L) following inhalation of insulin than when the placebo was used. On the insulin visit, glucose levels were < 11.2 mmol/L 2 h after the meal in six of seven patients. None attained this level at the placebo visit. In addition, glucose levels were within the normal postprandial range of < 7.84 mmol/L in eight of ten patients 2 h after eating on the insulin visit.

Conclusions: These results suggest that, once plasma glucose levels are normalized, postprandial glucose levels can be maintained below diabetic levels by delivering 1.5 U/kg insulin into the lungs 5 min before the ingestion of a meal.

 

IMPROVEMENT OF EARLY-PHASE INSULIN RESPONSE AND GLUCOSE TOLERANCE BY RHEIN IN db/db MICE

H. Du (1), J. Shao (1), P. Gu (1), B. Lu (1), J. Wang (1), Z. Liu (2)

1 Department of Endocrinology, Nanjing General Hospital of Nanjing Military Command, Nanjing, China

2 Research Institute of Nephrology, Nanjing Jinling Hospital, Nanjing, China

 

OBJECTIVE Rhein (4,5-dihydroxyanthraquinone-2-carbxylic acid) is one of the most important active components of rhubarb (Rheum officinale), a traditional Chinese herb widely used to cure diseases associated with over-nutriention by Chinese emperors in ancient time. Recently, it has been found to be valuable in chronic inflammatory diseases. In the present study, we aimed to investigate whether rhein have effects on insulin secretory function and glucose tolerance in diabetic db/db mice.

METHODS Thirty 4-week-old db/db mice were randomized to treatment with rhein (120mg/Kg) and placebo (1% natrium cellulose solution) by gavage for 8 weeks respectively. Age-matched non-diabetic littermates db/m mice treated with placebo were studied as non-diabetic control. Body weight and blood glucose level were measured every week. After 8 weeks’ treatment, IPGTT was done and immunohistochemical staining of insulin was performed to estimate beta-cell mass. AUC (area under curve) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. Islet isolation and perifusion were performed to evaluate kinetics of insulin release in vitro, especially first-phase insulin.

RESULTS In rhein-treated group, the blood glucose concentrations at 0min, 60min and 120min after glucose load were significantly reduced. Simultaneously measured insulin levels at 30min and 60min were significantly higher than those of control. Perifusion showed that rhein-treated group manifested a significantly increase of first-phase insulin secretion. Concurrently, rhein treatment greatly preserved beta cell mass and inhibited beta cell apoptosis.

CONCLUSIONS Rhein treatment significantly improved glucose tolerance by preservation of beta cell mass and inhibition of beta cell apoptosis in db/db mice.

 

EFFECTS OF ORAL HYPOGLYCEMIC DRUGS IN COMBINATION WITH ANTIOXIDANT (HONEY) ON GLYCEMIC CONTROL AND METABOLIC PARAMETERS IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

O.O. Erejuwa (1), S.A. Sulaiman (1), M.S. Ab Wahab (1), K.N.S. Sirajudeen (2), S. Md. Salleh (3), S. Gurtu (4)

1 Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia

2 Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia

3 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia

4 School of Medicine and Health Sciences, Monash University Sunway Campus, Jalan Lagoon Selatan, Selangor, Malaysia

 

Diabetes mellitus is characterized by worsening glycemic control and metabolic derangements. This study investigated the effects of addition of honey to hypoglycemic agents on glycemic control and metabolic parameters in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by STZ (60 mg/kg; ip). The diabetic rats were randomly divided into six groups and administered distilled water, honey, metformin, metformin and honey, glibenclamide or glibenclamide and honey. The rats were treated by gavage once daily for four weeks. Hypoinsulinemia (0.27 ± 0.01 ng/ml), hyperglycemia (22.4 ± 1.0 mmol/L) and increased fructosamine levels (360.0 ± 15.6 µmol/L) were observed in the serum of diabetic rats. Honey significantly increased insulin concentration, reduced hyperglycemia and fructosamine levels. Metformin or glibenclamide alone significantly reduced hyperglycemia (13.2 ± 2.9 or 13.9 ± 3.4 mmol/L, respectively) in diabetic rats. However, addition of honey to metformin or glibenclamide resulted in much lower levels of blood glucose (9.9 ± 3.3 or 8.8 ± 2.9 mmol/L, respectively). Similarly, honey combined with metformin or glibenclamide produced significantly lower fructosamine levels (285.8 ± 22.6 or 301.3 ± 19.5 µmol/L, respectively). In contrast, metformin or glibenclamide alone did not decrease fructosamine (314.6 ± 17.9 or 330.0 ± 29.9 µmol/L, respectively). Besides, these drugs or their combination with honey increased insulin. Metformin or glibenclamide combined with honey also significantly reduced the levels of creatinine, bilirubin, triglycerides and VLDL cholesterol. This study shows that addition of honey to hypoglycemic drugs further reduces serum glucose and fructosamine and offers beneficial metabolic effects, not achieved with either drug alone.

 

EFFICACY OF DPP-4 INHIBITORS AND PREDICTIVE FACTOR FOR THE TREATMENT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

J.R. Hahm (1), S.M. Lee (1), T.S. Jung (1), J.H. Jung (1), S.I. Chung (1)

1 Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju city, South Korea

 

Background: The object of study is to evaluate the efficacy of Dipeptidyl polypeptidase-IV inhibitors (DPP-4 inhibitors) to type 2 diabetes patients who were not well controlled with other oral hypoglycemic drugs or insulin, and to evaluate the predictive factors that influence on glucose lowering effect.

Methods: Retrospective study of the efficacy of DPP-4 inhibitors was done for whom diagnosed with type 2 diabetes patients, but not reached glycemic control target (glycated hemoglobin > 6.5%). I evaluated the changes of glycated hemoglobin, fasting plasma glucose, postprandial 1 hour plasma glucose, and level of fasting plasma C-peptide. I investigated diabetic microvascular complications at the beginning of study.

Results: Total 156 patients were enrolled and followed up for 8.5 months. At the study end, patients receiving DPP-4 inhibitors had a mean decrease in glycated hemoglobin of 0.67%, and in fasting plasma glucose, and postprandial plasma glucose from baseline of 16 mg/dL, 32 mg/dL respectively (p < 0.005). Responders (n=107, 68.6%) had features of short duration of diabetes (7.7±7.1 years versus 10.6±6.8 years; p=0.015), less microvascular complications, such as diabetic neuropathy (16.8% versus 36.7%; p=0.006) compared to non-responders (n=49, 31.4%).

Conclusion: A clinical meaningful improvement in glycemic control to type 2 diabetes patients who were previously treated with other oral hypoglycemic drugs or insulin was seen with concomitant DPP-4 inhibitors therapy. Patients who had short duration of type 2 diabetes and who had no combined microvascular complication were more easily achieved to glycemic target with concomitant use of DPP-4 inhibitors.

 

COMPARATIVE INVESTIGATION OF PIOGLITAZONE, METFORMIN AND THE COMBINATION OF BOTH AS ADD- ON THERAPY IN PATIENTS ON HIGH CARDIOVASCULAR RISK DESPITE STABLE INSULIN TREATMENT WITH INSULIN GLARGINE

M. Hanefeld (1), I. Kleine (2), A. Pfützner (3), W. Fuchs (2), T. Forst (3)

1 GWT-TUD mbH - Centre for Clinical Trials

2 Takeda Pharma GmbH

3 IKFE Mainz

 

Patients with long term type 2 diabetes with stable insulin therapy still exhibit a high cardiovascular (CV) risk. We analyzed specific effects of add on therapy with pioglitazone in comparison with metformin and their combination in type 2 diabetes patients on high CV risk, despite acceptable HbA1c control with basal insulin glargine. In this double blind randomized active comparator controlled trial 121 patients with type 2 diabetes were included. Inclusions: stable insulin treatment, HbA1c > 6.5% < 8.5%, age 30-75 years. Patients: 63.0 (± 7.5) years, BMI 32.2 (± 5.3), HbA1c 7.34 (± 0.53), insulin glargine dosage 36.2 (± 20.9) units. Comorbidities: hypertension 87,6%, CVD 19%. After a run in phase of >2 weeks with glargine monotherapy titrated to FBG < 7.8mmol/l patients were randomized to either (A) bid 850mg metformin (B) bid 15mg pioglitazone or (C) 30mg pioglitazone plus 1.7g metformin for a treatment of 6 months. Primary objective: MMP-9. These patients still exhibit an increased inflammatory activity, hsCRP of 3.21 mg/l, MMP9 of > 550ng/ml at baseline. Pioglitazone but not metformin significantly reduced MMP-9 and hsCRP and increased insulin sensitivity and adiponectin independent from glycemic control. All significantly reduced PAI-1. The triple combination of pioglitazone with metformin resulted in better HbA1c without added effect on inflammation and fibrinolysis. No serious adverse events were observed. Weight change was -0.7kg vs. +4.3kg vs. +2.7kg and peripheral edema were observed in 11.9% vs. 40.0% vs.20.5% in groups 1, 2 and 3. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high cardiovascular risk because it closes a gap in prevention of CVD by correction of increased inflammatory activity and insulin resistance.

 

THE OUTCOME OF BETA CELL FUNCTION AFTER EARLY INSULIN THERAPY IN THE RECENTLY DIAGNOSED TYPE 2 DIABETES (IN EGYPTIAN POPULATION) OUR EXPERIENCE IN EL-MINIA UNIVERSITY HOSPITAL

Y.M. Mosa (1), A.M. Mohamed (1), S.H. El Hini (1), M.S. Kamel (1), A.S. Salama (1), G.M. El Sagheer (1), A.M. Osman (2)

1 Internal medicine department, Minia University, Egypt

2 Clinical Pathology Department, Minia University, Egypt

 

The purpose of this prospective cohort study was to evaluate whether early insulin therapy is more advantageous in achieving long-term optimal glycemic control with improved B cell function than oral drugs in the recently diagnosed type 2 diabetes mellitus. Methods: Sixty consecutive patients with recently diagnosed type 2 diabetes mellitus were divided into 3 groups .The 1st group received 2 SC injections of premixed insulin. The 2nd group received bed time NPH and 3 injections of regular insulin before meals. The 3rd group received metformin and/or sulphonylureas. The treatment continued for 3 months till euglycemia was reached. Then, all medications were stopped and the patients were followed up till the end of the year. BMI, FBG, PPG, HbA1C, fasting level of insulin, proinsulin, C- peptide, HOMA-IR, HOMA-B, serum cholesterol, triglycerides were estimated. Results: Six patients from group I (30%), nine from group II (45%), and only one from group III (5%) succeeded to maintain euglycemia without further therapy for 9 months after stoppage of treatment. The mean HbA1C level was 6.5% in group I, 6.1% in group-2, and >7% in the group-3. Level of HbA1C in the succeeded patients declined significantly in comparison to the failed patients. Markers of B- cell function of the succeeded patients showed a statistical significant increase regarding the C-peptide, insulin and HOMA-B. Meanwhile, proinsulin level declined from 24.99±0.99 before treatment to 18.2±5.1 after treatment (P=0.0001) and proinsulin / insulin ratio declined from 40.9±14.5 before treatment to 18.19±5.13 after treatment (P=0.0001). The total serum cholesterol declined from 206. 3± 36.7 before treatment to 176.3±42.3 (P=0.001) and triglycerides reduced significantly from 213.9 ±79.1 before treatment to 160.3±54.4 after treatment (P=0.001) of insulin treated groups Conclusions: Short-term insulin therapy in a newly diagnosed type 2 diabetes insulin naive patients can preserve B- cell function and insulin secretion, allowing long-term glycemic control without medication and may improve glycemic responses to supplemental oral treatment if needed.

 

EFFECT OF THERAPEUTIC SUPPLEMENTATION AND LIFE STYLE INTERVENTION IN THE MANAGEMENT OF HYPERTENSION AMONG SMOKERS

R. Ranganathan (1), R. Gunalan (1)

1 Avinashilingam Deemed University for Women, Coimbatore, India

 

Hypertension is 21st century’s pandemic. It is a commonly occurring disorder with a high degree of clinical, health and economic importance. Smoking is considered to be one of the main causative factors contributing to hypertension.  The study was planned with an objective to assess the role of Oats, Green gram and selected herbs in controlling hypertension among smokers. One hundred and fifty smokers working in an industry were selected and their blood pressure, anthropometric measurements, their life style, habits, medical history and dietary intakes etc were obtained through an interview schedule. A subsample of 30 hypertensive smokers were selected for the two groups namely experimental and control group. A porridge consisting of 25 grams of oats (avena sativa), 10 grams of green gram (vigna radiata), and 2 grams of Agathi (sesbania grandiflora), Mint (menthe arvensis), Tulsi (ocimum sanctum), Hibiscus (rosa sinesis), Curry leaves (murraya koenigii) and 3 gms of jaggary were given to experimental group (N=15) everyday for a period of 60 days. Along with the supplementation, the subjects were also given training in yoga and meditation. An educational package has been prepared to impart knowledge to the subjects about the importance of diet, physical activity, basic education on hypertension and its monitoring. Control group (N=15) did not receive any supplement. Blood pressure was monitored before and after supplementation for both the groups and the results show that there is a significant change (P<0.01) in systolic and diastolic blood pressure on the selected subjects of experimental group after supplementation. Thus it can be concluded that the supplementation and lifestyle intervention had a significant impact on lowering blood pressure of hypertensive smokers.

 

THE EFFECTS OF TELMISARTAN ON FIRST-PHASE INSULIN SECRETION INVITRO IN db/db MICE

J. Shao (1), P. Gu (1), H. Du (1), B. Lu (1)

1 Department of Endocrinology, Nanjing General Hospital of Nanjing Military Command, Nanjing, China

 

Objective: Several epidemiological studies suggested that treatment with angiotensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. Yet the mechanisms remain to be elucidated. The aim of present study was to explore the effects of telmisartan on first-phase insulin secretion of islets in vitro on db/db mice. Methods: Eighteen db/misty mice, 8 weeks of age, were randomized to three groups as A, B, and C with 6 mice in each group.  Twelve age-matched db/db mice were randomized to two groups as D and E. After islet isolation, islets of A~E group were incubated and perfused with medium adding blank, 100 nmol /L Ang‡U, 10ƒֺmol/L telmisartan +100 nmol /L Ang‡U, blank, and 10ƒֺmol/L telmisartan respectively. The islets were stimulated in the continuous presence of a high concentration of 16.7 mmol/l glucose. Samples were collected at multiple time points until 30-min after 16.7mM glucose solution perifusion for insulin measurement.

Results: First-phase insulin secretion of db/misty was significantly impaired by AngII, with its peak only reached 4 times of basal level. While telmisartan beforehand improved its secretion to 7 times of basal level. First-phase insulin secretion of db/db was greatly diminished to a extent of lower than 3ug/L, while telmisartan improved its secretion to 6ug/L.

Conclusions: By blocking local RAS, Telmisartan intervention remarkably improved first-phase insulin secretion of islets in vitro on db/db mice, thus protected ƒְ-cell function. And this may contribute to the mechanisms of its anti-diabetic benefits.

 

THE PROTECTIVE EFFECTS OF TELMISARTAN ON INTRA-ISLET MICROVASCULARE IN db/db MICE

J. Shao (1), P. Gu (1), H. Du (1), B. Lu (1)

1 Department of Endocrinology, Nanjing General Hospital of Nanjing Military Command, Nanjing, China

Objective: Several epidemiological studies suggested that treatment with angiotensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. Yet the mechanisms remain to be elucidated. The aim of present study was to explore the effects of telmisartan on intra-islet microvasculature in db/db mice.

Methods: Twenty-two db/db mice, 8 weeks of age, were randomized to telmisartan 5mg/kg and placebo via gavage for 6 weeks. Eleven age-matched db/misty mice were studied concurrently treated with placebo as non-diabetic controls. Body weight and random blood glucose were measured every week. After 6 weeks’ treatment, Intraperitoneal glucose tolerance test, immunohistochemical staining of platelet endothelial cell adhesion molecule 1 (PECAM1) were porformed. Islets were isolated and perifusion were performed to evaluate kinetics of insulin release by using islet perfusion system. The ultrastructure of intra-islet microvasculature was observed by electron microscopy.

Results: Six weeks’ telmisartan treatment improved glucose tolerance, insulin secretory function and insulin sensitivity. And islet beta-cell mass was greatly rescued. Telmisartan treatment also improved first-phase insulin response. And telmisartan treatment greatly increased expression levels of PECAM1 in islets. Electron microscopy showed more fenestration and caveolae in Telmisartan treatment group. These results indicate that the beneficial effects of telmisartan on glucose metabolism at least partly due to improved quality and quantity of blood vessels in the islets.

Conclusions: Telmisartan treatment remarkably increased intra-islet microvasculature volume, and improved early-phase insulin secretion, thus protected beta-cell function.

 

GYNOSTEMMA PENTAPHYLLUM EXTRACT IMPROVES INSULIN SENSITIVITY IN TYPE 2 DIABETIC PATIENTS

H.T.T. Vu (1,2,3), P.V. Dao (2), T. Pham (3), H.K. Nguyen (4), C.G. Ostenson (1)

1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

2 Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam

3 Department of Endocrinology and Diabetes, National Institute of Gerontology, Hanoi, Vietnam

4 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada


Aims: To evaluate the effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP) extract on insulin sensitivity in drug-naןve type 2 diabetic patients.

Methods: Sixteen patients completed the randomized, double-blind, placebo-controlled crossover clinical trial. Patients received GP or placebo extract 6g daily for four weeks and vice versa with a 2-week washout period. At the end of each period, a Somatostatin-Insulin-Glucose Infusion Test (SIGIT) was performed. Fasting plasma glucose (FPG), HbA1C, oral glucose tolerance tests and insulin levels were measured before, during and after the treatment.

Results: FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment compared to placebo treatment (p < 0.001). The levels of FPG in the control group were slightly reduced 0.2 ± 1.5 vs. 1.9 ± 1.0 mmol/L in GP group (p < 0.001) and the effect on FPG was reversed after exchanging treatment. The glycometabolic improvements were achieved without any major change of circulating insulin levels. There were no changes in lipids, body measurements, blood pressure and no reported hypoglycemias, or acute adverse effects regarding kidney and liver parameters.

Conclusion: The results of this study clearly demonstrated that the GP extract exerted anti-diabetic effect by improving insulin sensitivity. The safety of GP extract was again proved clinically in the trial. This study is registered at ClinicalTrial.gov with ID: NCT01254084.

 

TRIGONELLA FOENUM GRAECUM SEED EXTRACT PROTECTS AGAINST FUNCTIONAL AND MORPHOLOGICAL ABNORMALITIES IN KIDNEYS OF DIABETIC RATS VIA ITS ANTIOXIDANT ACTIVITY

W. Xue (1)

1 Department of Public Health, Xi’an Jiaotong University School of Medicine

 

Oxidative stress is involved in the development and progression of diabetic nephropathy (DN). Because Trigonella foenum graecum has been reported to have antidiabetic and anti-oxidative effects, we hypothesized that Trigonella foenum graecum seeds aqueous extract (TE) restores kidney injuries of diabetic rats via its antioxidant activity. Rats were fed diets enriched with sucrose (50%, w/w), lard (30%, w/w) and cholesterol (2.5%, w/w) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin, the rats were administered a low (440 mg/kg), medium (870 mg/kg) or high (1740 mg/kg) dose of TE by oral intragastric intubation for 6 weeks. In TE-treated DN rats, blood glucose, kidney/body weight ratio, serum creatinine, blood urea nitrogen, 24-h content of urinary protein and creatinine clearance were significantly decreased compared to non-treated DN rats. Diabetic rats showed decreased activities of superoxide dismutase and catalase, increased concentrations of malondialdehyde in the serum and kidney, and increased levels of 8-hydroxy-2Œ- deoxyguanosine in urine and renal cortex DNA. Treatment with TE restored the altered parameters in a dose-dependent manner. Furthermore, all the ultramorphological abnormalities in the kidney of diabetic rats, including the uneven thickening of the glomerular base membrane, were markedly ameliorated by TE treatment. We conclude that TE confers protection against functional and morphological injuries in kidneys of diabetic rats by increasing activities of antioxidants and inhibiting accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.

 

ALTERNATIVE THERAPY OF ARTERIAL HYPERTENSION WITH PRESTARIUM IN OLD PATIENTS WITH DIABETES MELLITUS, TYPE II AND NEPHROPATHY (POLYMORBIDY SYNDROME)

R. Zaslavskaya (1), S.V. Sergeev (1)

1 Hospital N60, Russia

 

Aim: to study different approaches to treatment with prestarium (Servie, France) of old pts with arterial hypertension (AH) together with polymorbidy syndrome (PS).

Material and methods: 60 pts (mean age – 73 years old) with AH together with diabetes mellitus, type II, adipositas, nephropaty, dislipidemia, were divided into three groups with 20 pts in each. The 1st group received prestarium (P) (tert-butilamine salt) in a dose of 4 mg twice a day. The second group received prestarium A(PA) (arginin salt) in a dose of 5 mg once a day, in the chronotherapy (CT) regimen (4 hours before BP increased by BP-monitoring data with taking into account pharmacokinekics). The 3-rd group obtained PA in the morning and melaxen (melatonin, Unipharm, USA) in a dose of 3 mg at 22.00. Before and after all types of therapy during 21 days pts were investigated by clinic-laboratory examination, ECG, BP-monitoring, EchoCG.

Results: all methods of therapy produced antihypertensive effect (on the 4 day) statistically significant. But circadian profile changed better in (CT) with PA and with therapy of PA together with melaxen. Daily and course doses of PA in regimen CT were smaller, than of prestarium (tert-butilamine salt). Circadian profile of BP in pts with non-dipper transfered in dipper. The same data was in therapy with combination PA together with melaxen. Circadian organization of BP rhythm normalized. Traditional therapy with prestarium (tert butilamine salt) did not make this effect. Levels of glucose, insulin, creatinin, urea in blood did not changed.

Conclusion: treatment with prestarium A in chronotherapy regimen and this drug with melaxen in old pts with AH and polymorbidy syndrome is more effective than traditional therapy with prestarium (tert butilamine salt).

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