Affiliation:
1. Pirogov Russian National Research Medical University
Abstract
Type 2 diabetes mellitus (T2DM) is a polygenic disease that develops as a result of the interaction of hereditary predisposition and environmental factors. The predisposition to develop T2DM is associated with the inheritance of certain alleles of “healthy” genes. More than 100 polymorphic variants of genes that increase the risk of developing T2DM have already been described. Today, genes predisposing to the development of β-cell dysfunction and insulin resistance (IR) are the most well studied. In addition, genes that affect lipid metabolism and eating behavior and genes of some cytokines can participate in the formation of a genetic predisposition to the development of T2DM. Our article reviews the most promising potential areas of application of knowledge about the genetics of T2DM in clinical practice. The first direction is to specify the classification and stratification of T2DM into subclasses/clasters. The second one is an individual assessment of the risk of developing T2DM and its complications. Today, predictive models of the risk of developing type 2 diabetes are not accurate enough for widespread use in clinical practice, but now researchers are actively working to improve their accuracy and effectiveness. And finally, knowledge about the genetics of T2DM can help predict the effectiveness of glucose-lowering therapy. In this review, we also discuss the topic of metabolic disease endophenotypes. The concept of endophenotypes suggests the presence of certain pathogenic common links in the pathogenesis of IR, obesity, T2DM, cardiovascular diseases, non-alcoholic fatty liver disease and chronic kidney disease, which are based on certain polymorphic gene variants. The results of research in the field of genetics of T2DM give us new possibilities for a personalized approach to the management of this complex disease.