UC Irvine

Diabetes mellitus is the leading cause of end-stage renal disease (ESRD) in the U.S. and many countries globally. The role of improved glycemic control in ameliorating the exceedingly high mortality risk of diabetic dialysis patients is unclear. The treatment of diabetes in ESRD patients is challenging, given changes in glucose homeostasis, the unclear accuracy of glycemic control metrics, and the altered pharmacokinetics of glucose-lowering drugs by kidney dysfunction, the uremic milieu, and dialysis therapy. Up to one-third of diabetic dialysis patients may experience spontaneous resolution of hyperglycemia with hemoglobin A1c (HbA1c) levels <6%, a phenomenon known as Burnt-Out Diabetes, which remains with unclear biologic plausibility and undetermined clinical implications. Conventional methods of glycemic control assessment are confounded by the laboratory abnormalities and comorbidities associated with ESRD. Similar to more recent approaches in the general population, there is concern that glucose normalization may be harmful in ESRD patients. There is uncertainty surrounding the optimal glycemic target in this population, although recent epidemiologic data suggest that HbA1c ranges of 6% to 8%, as well as 7% to 9%, are associated with increased survival rates among diabetic dialysis patients. Lastly, many glucose-lowering drugs and their active metabolites are renally metabolized and excreted, and hence, require dose adjustment or avoidance in dialysis patients.