Diabetic nephropathy in novel diabetes subphenotypes Diabetic nephropathy and insulin resistance

Insulin resistance as it occurs in diabetes and obesity is associated with impaired renal function and can lead to end-stage renal disease. In 3 independent studies it was demonstrated that a subphenotype of type 2 diabetes, which is characterized by severe peripheral insulin resistance, demonstrated a particularly high risk for the development and progression of diabetic nephropathy. Therefore, the determination of a panel of metabolic markers, in particular markers of insulin resistance in the initial diagnosis of diabetes, is superior to the measurement of glucose alone and unmasks this subphenotype of diabetes. The patients in the severe insulin-resistant diabetes (SIRD = cluster 3) group already had a reduced estimated glomerular filtration rate (eGFR) and elevated cystatin C values at baseline and demonstrated the highest prevalence for stages 2 and 3 of chronic kidney disease and the highest risk for the development of end-stage renal disease at baseline and after 5 years follow-up despite relatively good metabolic control. These findings support the hypothesis that peripheral insulin resistance and the association with inflammation play an important pathophysiological role in the development and progression of diabetic nephropathy. It can be postulated that the unmasking of high-risk subtypes of type 2 diabetes will enable timely, intensified and tailored treatment as part of a precision medicine approach, to prevent the development and progression of diabetic nephropathy as well as other diabetic complications (neuropathy, retinopathy, fatty liver and liver fibrosis).