[show abstract][hide abstract] ABSTRACT: The KCNJ11 and ABCC8 genes encode components of the pancreatic ATP-sensitive potassium (KATP) channel. Previously, we reported
association of the KCNJ11 E23K and ABCC8 R1273R G/A variants with type 2 diabetes (T2D) in a small Russian population sample
(n=244). Here we replicated association between these genetic variants and T2D in a larger cohort (588 diabetic and 597 non-diabetic
subjects). Using the ANCOVA analysis, Odds Ratios (ORs) and relationships between the carriage of a genotype and biochemical
parameters of the patients were assessed and then adjusted for confounders (age, gender, HbA1c, hypertension, and obesity).
The KCNJ11 K23 variant and the ABCC8 R1273R allele A showed association with higher risk of T2D (adjusted OR of 1.41 and 2.03,
P<0.0001, respectively). Diabetic patients homozygous for K/K had lower 2h insulin (Padjusted=0.044). The ABCC8 A/A variant was associated with increased 2h serum insulin in diabetic and non-diabetic subjects (Padjusted=0.027 and 0.033, respectively). The carriage of the risk variant K/K of KCNJ11 E23K or A/A of ABCC8 G/A R1273R was associated
with reduced response to nonsulfonylurea and sulfonylurea blockers of the pancreatic KATP channel. Adjusted attributable population
risk was 3.0% (KCNJ11 E23K) and 4.8% (ABCC8 G/A) suggesting for the modest effects of these genetic variants on diabetes susceptibility.
Central European Journal of Biology 04/2012; 5(1):67-77. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: The second isoform of the PPARgamma2 is specific for adipose tissue. In adipocytes, this isoform is involved in the regulation of adipogenesis and lipid storage, insulin and glucose metabolism. Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with increased insulin sensitivity and protection from T2D. Previously, this polymorphism has never been assessed in a Russian population for its relationship to T2D, insulin resistance, and diabetes-related metabolic traits. In this study, we tested 588 Russian T2D patients and 597 normoglycaemic controls. Carriers of the Pro12 allele and subjects homozygous for Pro/Pro had significantly increased risk of developing T2D (OR 1.43 and 2.04, respectively). In Pro/Pro homozygotes, adjustment for potential confounding risk factors resulted in reducing the OR value from 2.04 to 1.69, but the association remained significant (p=0.046).The Pro/Pro genotype also showed association with increased levels of fasting insulin (p=0.019) in non-diabetic controls and elevated serum triglycerides (p=0.019) in T2D patients. Compared with other genotypes, non-diabetic and diabetic subjects homozygous for Pro/Pro had a significantly higher HOMA-IR score and reduced ISI value. This observation strongly supports the implication of the PPARG Pro12Ala in insulin resistance and T2D in a Russian population.
[show abstract][hide abstract] ABSTRACT: To determine risk factors, prognostic, value prevention of development of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM).
We have retrospectively analyzed the incidence of CIN developed after PCI in 151 patients T2DM and 50 patients without diabetes. All patients were subjected to thorough clinical examination (including serum creatinine level before and 48 hours after intervention).
CIN developed more frequently after PCI in patients with T2DM than in patients of the same age without diabetes at the same baseline renal function, volume of contrast media and hydration status. The risk of developing CIN in patients with T2DM is associated with: heart failure, anemia, volume of contrast media, diuretics use in the peri-procedure period, multiple coronary artery disease, need of interventional procedures. TIDM patients with CIN had faster decline of renal function, more often developed cardiovascular diseases and had lower 24 month survival rate.
High risk of CIN development and its prognostic significance in patients with T2DM determine the necessity of individually evaluated risks for preventive measures during contrast media interventions.
Diabetes research and clinical practice 12/2009; 86 Suppl 1:S63-9. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: AimsMarkers rs12255372 (G/T) of the transcription factor 7-like 2 (TCF7L2) and rs13266634 (R325W) of the solute carrier family 30 (zinc transporter) member 8 (SLC30A8) showed association with type 2 diabetes (T2D) in multiple ethnic groups. In this study, we evaluated whether these markers confer susceptibility to T2D in a Russian population.Methods
Using a direct DNA sequencing, we genotyped these markers in 588 unrelated Russian T2D patients and 597 normoglycemic non-diabetic controls at age 50 and older. Association between these markers and patients’ clinical and metabolic traits was assessed by the ANCOVA analysis, with adjustment for possible confounding risk factors.ResultsThe allele T of rs12255372 and allele R of rs13266634 showed significant association with a higher diabetes risk (Odds Ratio (OR) = 1.37 and 1.22, respectively). Adjustment for confounding risk factors strengthened the association increasing OR from 1.54 (p = 0.24) up to 1.89 (p = 0.046) in homozygotes T/T and from 1.29 (p = 0.035) up to 1.35 (p = 0.019) in homozygotes R/R. Compared to other genotypes, homozygous carriers of the risk variants of TCF7L2 and SLC30A8 (both diabetic and non-diabetic) had significantly lower levels of 2 h insulin and decreased values of the homeostasis model assessment of β-cell function (HOMA-β).ConclusionsTCF7L2 rs12255372 and SLC30A8 rs13266634 modulate risk of T2D in a Russian population through impaired function of β-cells.
Diabetes and Metabolic Syndrome Clinical Research and Reviews 12/2009; 3(4):219–223.
[show abstract][hide abstract] ABSTRACT: The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates
insulin secretion by β-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and
ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) approach. The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with
higher risk of T2D [Odds ratio (OR) of 1.53 (P = 0.023) and 2.41 (P = 1.95 × 10−5)], respectively. Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A + A/G (P = 0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in
diabetic and non-diabetic patients. A HOMA-β value characterizing the β-cell homeostasis was higher in the non-diabetic carriers
homozygous for G/G (98.0 ± 46.9) then for other genotypes (HOMA-β = 85.6 ± 45.5 for A/A + A/G, P = 0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and
altered insulin secretion in a Russian population.
[show abstract][hide abstract] ABSTRACT: Alterations in adiponectin-mediated pathways are known to be associated with glucose intolerance, insulin resistance (IR), obesity, and type 2 diabetes (T2D) mellitus. Genetic variations in adiponectin (ADIPOQ) and adiponectin 1 and 2 receptor (ADIPOR1 and ADIPOR2) could have effects on IR-related phenotypes and T2D. Here we examine whether the polymorphic markers rs2241766 (ADIPOQ), rs22753738 (ADIPOR1), rs11061971 and rs16928751 (both in ADIPOR2) are implicated in susceptibility to T2D in a Russian population.
The polymorphic markers were genotyped in 129 T2D patients, and 117 non-diabetic controls, by polymerase chain reaction (PCR) restriction fragment length polymorphism approach. In the subjects, biochemical characteristics including serum insulin, plasma glucose and serum lipids/lipoproteins were measured and compared for correlation with the genetic variations studied.
Allele T of rs11061971 and allele A of rs16928751 showed association with higher risk of diabetes providing odds ratios (OR) of 2.05 (p = 0.0025) and 1.88 (p = 0.018), respectively. Haplotype A-G consisting of allele A of rs11061971 and allele G of rs16928751 was associated with reduced risk of T2D (OR = 0.59, pc = 0.0224). Compared to other variants, diabetic patients double homozygous for A/A of rs16928751 and G/G of rs16928751 had decreased homeostasis model assessment-insulin resistance (pc = 0.0375) and serum triglycerides (pc = 0.0285).
The variants of ADIPOR2 confer susceptibility to T2D and are associated with some IR-related phenotypes in the Russian study population.
The Review of Diabetic Studies 02/2008; 5(1):28-37.
[show abstract][hide abstract] ABSTRACT: Aims
The KCNJ11 and ABCC8 genes encode components of the ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by β-cells. Alterations in the activity of pancreatic KATP could be involved in the pathogenesis of type 2 diabetes (T2D). We studied the KCNJ11 E23K and ABCC8 exon 31 variants for association with T2D, glucose intolerance and altered insulin secretion in a Russian population.
Using a polymerase chain reaction (PCR) with the following digestion of a PCR product with a corresponding restriction enzyme, genomic DNA from Russian T2D patients (N = 127) and controls (N = 117) were genotyped. Fasting and 2 h glucose and insulin were measured in blood of all subjects studied. Biochemical parameters in diabetic and control individuals were compared by the unpaired Student's t-test. χ2-test was used to compare allele and genotype frequencies of the polymorphisms studied.
The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D (Odds Ratio (OR) of 1.53 (p = 0.023) and 2.41 (p = 1.95 × 10−5), respectively. T2D patients with the EE variant of KCNJ11 have elevated 2 h serum insulin (EE (87.3 ± 34.9 mU/l) vs. KK + EK (82.1 ± 31.1 mU/l), p = 0.038). Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A + A/G (p = 0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-β value characterizing the β-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0 ± 46.9) than for other genotypes (HOMA-β = 85.6 ± 45.5 for A/A + A/G, p = 0.0015).
The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.
Diabetes and Metabolic Syndrome Clinical Research and Reviews 01/2008; 2(3):185-191.