Glucose Homeostasis, Hypoglycemia, and the Burnt-Out Diabetes Phenomenon in Kidney Disease

Chronic kidney disease (CKD) is among the most prevalent and dire complications of diabetes mellitus in adults across the world. Diabetes substantially contributes to the burden of kidney disease, such that one third to one half of CKD in the United States and many other countries is attributable to diabetic kidney disease (DKD). As DKD progresses to end-stage renal disease (ESRD), patients are at heightened risk for atypical glycemic complications, including the development of burnt-out diabetes, manifested by hypoglycemic bouts and poor outcomes. Furthermore, even in the absence of diabetes, hypoglycemia is a frequent occurrence in CKD patients that may contribute to their high burden of cardiovascular disease and death. Extrapolation of data from clinical trials in high-cardiovascular-risk populations and observational studies in patients with non-dialysis-dependent (NDD) CKD and ESRD suggest that moderate glycemic targets defined by glycated hemoglobin levels of 6% to 8% and glucose levels of 100 to 150 mg/dL are associated with better survival in DKD patients. However, given the imprecision of glycated hemoglobin levels in kidney disease, further research is needed to determine the optimal glycemic metric and target in diabetic NDD-CKD and ESRD patients. Given their exceedingly high cardiovascular morbidity and mortality, there is a compelling need for further investigation of how to optimally manage dysglycemia in the NDD-CKD and ESRD populations.