The global prevalence of diabetes mellitus (diabetes) reached 6.6% (285 million patients) in 2010 and is expected to be 7.8% (438 million patients) in 2030. Among patients with coronary heart disease, the incidence of diabetes is higher, than in the population, and the incidence of cardiovascular disease is higher in patients with diabetes. The Cardiovascular Health Study, which included individuals 65 years of age and older, found that the incidence of clinical or subclinical cardiovascular disease was 70% in individuals with normal glucose levels, 77% in people with advanced glucose, and 86% - for people with first-time diagnosed or verified diabetes mellitus
Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, is now recognized as a major public health problem worldwide. Tumor necrosis factor alfa (TNF-α), a member of the TNF/TNFR cytokine family, is an intercellular transmission molecule that has been reported in a wide range of human noninfection diseases. The aim of the study was to determine the circulating levels of TNF-α and the nature of its relationships with the components of insulin resistance, both metabolic and hormonal, in patients with type 2 diabetes; and establishing the nature of cardiovascular complications (taking into account TNF-α gene polymorphism) in the presence and absence of NAFLD.
Materials and methods. Case-control study included information about 50 practically healthy people from the city of Kharkiv and the region. The examined population (except control subjects) consisted exclusively of patients with type 2 diabetes mellitus with a long-term existence of the disease against the background of metabolic syndrome, with varying degrees of glycemic control and violations of liver homeostasis in the absence of renal failure. 117 people were selected for analysis: 63 of them with type 2 diabetes in the presence of NAFLD and 54 patients with type 2 diabetes without NAFLD. Genotyping for single nucleotide polymorphism -308 G>A of the TNF-α was performed by the method of polymerase chain reaction with appropriate primers and NcoI endonuclease. Testing of statistical hypotheses was carried out using the odds ratio and χ2 criteria at the significance level of P≤0.05.
Results. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.
No association of the studied polymorphism with the risk of developing NAFLD was found. The obtained data make it possible to assume that the studied polymorphism -308 G>A of the TNFα gene is more associated with the risk of developing type 2 diabetes, and the occurrence or progression of NAFLD primarily depends on metabolic imbalance, and not on the contribution of the studied polymorphism.
Conclusions. Non-alcoholic fatty liver disease is closely related to hormonal and metabolic risk factors and markers of cardiovascular disease and type 2 diabetes and may increase the risk of developing and progressing cardiovascular complications. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.
Single nucleotide polymorphism +276G > T of adiponectin gene (ADIPOQ) in type 2 diabetesmellitus patients (n=544) and healthy habitants (n = 215) of Kharkiv was studied. There wereno significant differences of single nucleotide polymorphism +276 G > T frequencies for patients(pG = 0.691; pT = 0,309) and healthy subjects (pG = 0,601; pT = 0,399). However diabetic patients hadincreased percentage of homozygote TT and decreased percentage of homozygote GG. Homozygosityin the minor allele T enhances significantly risk of disease in general population (OR 1,98; 95 %CI 1,14–3.32, p < 0.05) and homozygosity in the major allele G creates protective effect (OR 0,66; 95 %CI 0,48–0.90, p < 0.05). Functional meaning of single nucleotide polymorphism in the locus +276G > Tof ADIPOQ gene for hypoadiponectinemia genesis was verified as complementary to determiningimpact of diabetic endophenotype (hyperinsulinemia, insulin resistance, gluco- and lipotoxicity, centraltype of fat distribution).
Single nucleotide polymorphism (SNP) +45T/G gene of adiponectin (ADIPOQ) in type 2 diabetes mellitus patients and in healthy residents of Kharkiv has been taken into consideration. Frequencies of SNP +45T/G for patients (pG = 0,48; pT = 0,52) and healthy residents(pG = 0,49; pT = 0,51) do not differ significantly. The genotypes frequency in control group doesn’t correspond to HardyWeinberg equilibrium: the share of heterozygotes +45T/G is 1,8 times higher than selectively-neutral value. The type II diabetes mellitus patients have the share of heterozygotes +45T/G one third lower than in control group. The analysis has shown that heterozygotes genotype reduces the risk of type 2diabetes mellitus in seven times (p < 0,05) in comparison with a mean value in population.
61 middle-age overweight or obese patients with type 2 diabetes mellitus were studied. Patients were characterized by hormonal and metabolic parameters of insulin resistance (fasting hyperinsulinemia, both enhanced HOMA-IR indices and circulating free fatty acids levels, hypoadiponectinemia, hypertriglyceridemia). It was revealed significant increase in the circulating levels of osteoprotegerin, associated with macrovascular complications (ischemic heart disease, essential hypertension). It was also shown positive correlation of osteoprotegerin with retinol-binding protein 4, fetuin-A and progranulin. Our data support the perspective of circulating osteoprotegerin as new cardiovascular risk factor.
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