Genetics of complications in patients with type 2 diabetes

Abstract: Popular Abstract in English Type 2 diabetes (T2D) is a polygenic disorder characterized by impaired insulin secretion or insulin action in which genes interact with the environment to cause the disease. T2D represent 90% of all patients with diabetes. The disease is increasing globally, with an estimated prevalence of 592 million affected by 2035. According to World Health Organization records, approximately 80% of diabetes-related mortality occurs in low- and middle-income countries. The disease is associated with devastating complications such as chronic microvascular (nephropathy, retinopathy, and neuropathy) and macrovascular (coronary heart disease and stroke) consequences. Hyperglycaemia and duration of disease were considered the strongest risk factors for development of diabetic complications. Prospective studies have demonstrated that some patients with T2D experience complications despite well-controlled blood glucose levels, whereas some patients with uncontrolled blood glucose levels with long disease duration do not experience any complications. These observations suggest that genetic factors might be operative in the predisposition to diabetic complications. Also, family studies have reported 50% heritability for ischemic heart disease, 36% to 75% for diabetes nephropathy, and 52% for diabetes retinopathy. Our study aimed to (1) identify genetic markers associated with diabetic complications among patients with T2D, and (2) examine exposure of famine as a risk factor for progression to diabetes complications using susceptibility loci for cardiometabolic traits in T2D patients from Ukraine (a population with a high risk for cardiovascular disease). We have identified a genetic locus in the HMGA2 gene for association with DN and declined kidney function. Also, we identified a variant in the KCNJ11 gene to be associated with increased risks for all-cause and cardiovascular mortality among patients with T2D. Our data demonstrated a shared genetic susceptibility between microvascular and macrovascular complications in a Ukrainian population. Furthermore, the data suggest that famine exposure in early life can modify the risk for diabetes complications in adulthood.