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Bondar I.A.,Novosibirsk State Medical University | Filipenko M.L.,Institute of Chemical Biology and Fundamental Medicine | Shabel'nikova O.Y.,Novosibirsk State Regional Hospital | Sokolova E.A.,Institute of Chemical Biology and Fundamental Medicine
Diabetes Mellitus | Year: 2013

Aim: To investigate the association of polymorphisms in TCF7L2 and PPARG2 genes with type 2 diabetes mellitus (T2DM) in Novosibirsk population. Materials and Methods: We examined 391 patients with T2DM and 556 individuals with normal glucose metabolism. Allelic identification was performed with TaqMan technique, implementing allele-specific real-time PCR. Results: Analysis shows that allelic frequency distribution of rs1801282 variant of PPARG2 gene and rs7903146 variant of TCF7L2 differs significantly between the study and control groups (OR [CI 95%]=1.44 [1.12-1.85], p=0.005 and OR [CI 95%]=1.57 [1.17- 2.10], p=0.003, respectively). T2DM patients with T/T genotype of rs7903146 variant of TCF7L2 gene had lower BMI (p=0.02). Observed combination of risk alleles reached 99%. Combined β-cell dysfunction and insulin resistance genotypes were identified in 56% of tested subjects, isolated insulin resistance - in 42.2% of subjects, and isolated β-cell dysfunction - in 0.8% of subjects. Conclusion: Our data shows that carrier state of 12Pro rs1801284 variant of PPARG2 gene and T-allele rs7903146 variant of TCF7L2 gene are associated with T2DM in Novosibirsk population, increasing its risk 1.44 and 1.57 times, respectively. Combination of these polymorphisms was observed in 99% of patients with T2DM.


Bondar' I.A.,Novosibirsk State Medical University | Shabel'nikova O.Y.,Novosibirsk State Regional Hospital
Diabetes Mellitus | Year: 2013

More than 100 genes associated with the risk of type 2 diabetes mellitus (T2DM) are now established. Most of them affect insulin secretion, adipogenesis and insulin resistance, but the exact molecular mechanisms determining their involvement in the pathogenesis of T2DM are not understood completely.


Bondar' I.A.,Novosibirsk State Medical University | Demin A.A.,Novosibirsk State Medical University | Shabel'nikova O.Y.,Novosibirsk State Regional Hospital | Onyanova V.A.,Novosibirsk State Regional Clinical and Diagnostic Center
Diabetes Mellitus | Year: 2014

Aim: Atherosclerosis is one of the most important complications of type 2 diabetes mellitus (T2DM). In the present study, we aimed to assess the carotid intima-media thickness in type 2 diabetes patients with the arterial hypertension (AH) comorbidity. Materials and Methods: 96 patients with T2DM and AH (30M/66F, aged 53.4±5.4 years, duration of diabetes 7.7±7.5 years) and 30 hypertensive patients without diabetes (12M/18F, aged 53.1±6.0 years) were enrolled in this study. Stiffness indices for right and left common carotid arteries were assessed with noninvasive ultrasound method in both groups. Results: Difference in the intima-media thickness was statistically significant between diabetic and euglycemic patients (1.26±0.17 mm vs. 1.10±0.14 mm, respectively; p<0.01). Data from patients with diabetes duration less than 1 year was not significantly different from euglycemic controls (1.20±0.20 mm vs. 1.10±0.14 mm, respectively; p>0.05), in contrast with their counterparts with longer experience of T2DM (1.27±0.17 mm vs. 1.10±0.14 mm; p<0.05). In patients with AH and T2DM, intima-media thickness positively correlated with systolic blood pressure (r=0.521, p<0.01), duration of diabetes (r=0.203, p<0.05), fasting plasma glucose (r=0.215, p<0.05) and plasma HDL (r=-0.288, p<0.05). In euglycemic patients with AH we observed a correlation between the intima-media thickness and systolic blood pressure (r=0.284, p<0.05). Conclusion: Our data indicate that patients with AH and T2DM exhibit more profound alterations in the intima-media compared to their hypertensive but euglycemic counterparts. The increase in intima-media thickness in DM patients depends not only on the level of systolic blood pressure, but also on the duration of diabetes, on fasting plasma glucose and on plasma levels of HDL.


Bondar I.A.,Novosibirsk State Medical University | Demin A.A.,Novosibirsk State Medical University | Shabelnikova O.Y.,Novosibirsk State Regional Hospital
Diabetes Mellitus | Year: 2014

Objective: To evaluate morphological and functional parameters of the heart and vessels in patients with type 2 diabetes mellitus (DM2) and diabetic cardiovascular autonomic neuropathy (CAN). Materials and methods: A total of 139 patients with DM2 and hypertension (mean age: 53.1±4.9 years; mean duration of hypertension: 9.7±7.8 years) were included in this study. Based on cardiovascular autonomic function test results (electrocardiography, heart rate variability) patients were divided into 2 groups as follows: Group 1 included 40 patients without CAN and Group 2 included 99 patients with CAN. The control group comprised 30 patients with hypertension and normal carbohydrate metabolism (mean age: 53.1±6.0 years; mean duration of hypertension: 10.9±8.5 years). All patients underwent ultrasonography of the heart and common carotid artery. Results: Group 2 patients showed a significant decrease in maximal transmitral flow velocity during early diastolic filling (0.61±0.12 m/s) and a decrease in maximal transmitral flow velocity during late diastolic filling (0.65±0.11 m/s) compared with Group 1 patients (0.66±0.09 m/s and 0.69±0.09 m/s, respectively, p < 0.05) and control group patients (0.71±0.16 m/s and 0.69±0.14 m/s, respectively, p < 0,05). Further, Group 2 patients showed a significant increase in left ventricular mass and ventricular end-diastolic volume (253.3±67.2 g and 120.6±25.2 ml, respectively) compared with control group patients (204.6±72.7 g and 110.4±22.2 ml, respectively, p < 0.05) and a significant increase in intima-media complex thickness (IMT) (1.28±0.15 mm) compared with Group 1 patients (1.17±0.19 mm, p = 0.004). Conclusion: Increased left ventricular mass and heart volume parameters (end-systolic volume and end-diastolic volume), left ventricular diastolic dysfunction and increased common carotid artery diameter caused by increased IMT are the main determinants of CAN in patients with diabetes.


Bondar' I.A.,Novosibirsk State Medical University | Grazhdankina D.V.,Novosibirsk State Medical University | Ivanov S.V.,Novosibirsk State Regional Hospital | Panteleeva T.V.,Novosibirsk Tuberculosis Research Institute
Diabetes Mellitus | Year: 2013

Aims: To assess plasma level of N-terminal precursor for brain natriuretic peptide (proBNP) in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension without overt heart failure - and further estimation of its correlation with data from echocardiography and clinical parameters (severity of ischemic heart disease (IHD), age, sex, duration of T2DM and hypertension experience, characteristics of glucose and lipid metabolism, renal function. Materials and methods: We examined 94 patients with T2DM and arterial hypertension (aged 40-65 years), determining characteristics of glucose and lipid metabolism and renal function. We also performed six minute walk test, ECG, echocardiography and blood tests for N-terminal proBNP (NT-proBNP) in all study subjects. Acquired data was compared to the group of 30 healthy controls. Results: We observed an increase in plasma NT-proBNP in patients with IHD, history of left venctricular (LV) myocardial infarction or clinical signs of heart failure (II NYHA class and higher). Results from patients with T2DM and arterial hypertension but without IHD did not significantly differ from control group. Plasma NT-proBNP levels correlated with left ventricular ejection fraction, left ventricular EDD and ESD, but not with LV diastolic function parameters. Duration of T2DM and arterial hypertension, HbA1c levels BMI, lipid and uric acid metabolism parameters had no influence on plasma NT-proBNP in diabetic patients. Conclusion: According to our study, NT-proBNP was elevated in T2DM patients with IHD (and a history of LV myocardial infarction in particular) or clinical evidence for heart failure beyond II NYHA class, thus indicating unfavorable prognosis for this group of patients and need for correction of therapy with subsequent re-evaluation of plasma NT-proBNP.

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