The Influence of Hyperglycemia on Renin-Angiotensin System Activation in Diabetic Nephropathy

Abstract Diabetes mellitus (DM) is marked by hyperglycemia and may develop due to insulin deficiency or reduced insulin sensitivity. The global prevalence of DM was 14% in 2024, and it is estimated to elevate significantly by 2040. DM and its complications significantly influence patients and their families’ finances as well as nations’ economies. The complications of diabetes involve nephropathies, retinopathies, cardiovascular diseases, and neuropathies. Diabetic nephropathy is one of the most common long-term complications occurring in patients with DM. The renin-angiotensin system (RAS) is activated by hyperglycemia in diabetic patients and contributes to the development of diabetic nephropathy. The RAS consists of two non-classical and classical axes, which are mainly enzymes and peptides. Although the activation of the intrarenal RAS in diabetes is mentioned in previous studies, the influence of hyperglycemia on RAS activation in diabetic nephropathy is not well understood. The aim of this review is to summarize existing evidence focusing on the influence of hyperglycemia on RAS activation in diabetic nephropathy patients.