Non-Coding RNA in Type 2 Diabetes Cardio–Renal Complications and SGLT2 Inhibitor Response

Type 2 diabetes mellitus (T2DM) is characterized by uncontrolled increase in blood glucose levels, insulin resistance and metabolic inflammation. Vascular complication in T2DM have the inflammatory nature. Drugs with different mechanisms of action have been developed and used to treat T2DM, initially aimed to control blood glucose levels. Among them sodium-glucose cotransporter 2 inhibitors (SGLT2-i) were developed as specific inhibitors of glucose reabsorption in the kidneys, but along with lowering blood glucose levels, they demonstrated multiple (including non-glycemic) positive effects in the treatment of T2DM related to their beneficial effects on the immune system. SGLT2 inhibitors can reduce the risk of diabetic cardiomyopathy (DCM) and chronic kidney disease (CKD) development in patients with and without diabetes. SGLT2-is improve cardio-renal complications through a number of signalling pathways, including those dependent on the involvement of non-coding RNAs (ncRNAs) and their targets. The best-studied classes of ncRNAs are microRNAs, which are short (are less than 200 bases) RNAs (miRNAs), long non-coding RNAs (lncRNAs) (are more than 200 bases), and circular RNAs (circRNAs). The regulatory effect of ncRNAs has broad physiological significance, and changes in the ncRNAs expression are associated with the pathogenesis of different diseases including T2DM. RNA-seq allowed to construct networks of interactions of lncRNA/circRNA-miRNA-mRNA called competitive endogenous RNA (ceRNA) networks, to identify clinically significant molecular markers, to improve mechanistic understanding of pathogenesis, and to contribute to the development of new diagnostics and therapies. Our review summarizes the role of non-coding RNA in the action of SGLT2 inhibitors in cardio-renal complications in T2DM. We focus on methods of detection, genetics and mechanism of action of non-coding RNA. Specific attention is given to the role of non-coding RNAs in the inflammatory reactions of innate immune cells in relation to the SGLT2 inhibitors.