Type 2 diabetes (T2D) is a common metabolic disease characterized by insulin resistance and malfunction of pancreatic β-cells. A variety of inflammatory cytokines are involved in the pathogenesis of T2D. Inflammasome NLRP3 with caspase 1 activation leads to elevated IL1B levels. This also increases levels of IL6, impairing insulin function, and increases TNF levels, which reduce the expression of the insulin-regulated glucose transporter GLUT4. The objective of our genetic association retrospective study was to determine the influence of genetic polymorphisms in selected inflammatory cytokines on their regulation and occurrence of late complications. We enrolled 327 patients with T2D who were treated with various antihyperglycaemic agents. They received metformin (N=261), sulphonylurea (N=239), SGLT2 inhibitors (N=116) and GLP-1RA (N=69). The DNA of all subjects was isolated from blood samples or oral smears and genotyped using the KASP method. We found that rs35829419 NLRP3 was statistically significantly associated with the development of macrovascular complications when treated with sulphonylurea. IL1B polymorphisms rs1143623 and rs16944 were also statistically significantly associated with the development of retinopathy and nephropathy. We identified an association between IL6 rs1800795 and the development of retinopathy, as well as a group of microvascular complications in the metformin treatment group. TNF rs1800629 polymorphism was statistically associated with the development of microvascular complications with sulphonylurea treatment. The NLRP3, IL1B, IL6, and TNF polymorphisms did not affect glycated haemoglobin concentration, a marker of well-managed T2D. We have shown that genetic polymorphisms of inflammatory cytokines play an important role in the development of late complications of T2D, opening up new opportunities for personalized medicine and other treatment approaches in these patients.
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