Can improved glycemic control slow renal function decline at all stages of diabetic nephropathy?

Observational studies have shown the strong association between level of glycemic control and the key outcome measure, risk of glomerular filtration rate (GFR) loss rather than subsequent course of albumin excretion, in type 1 diabetes patients at all stages of nephropathy. However, it has not been clear if clinical interventions designed to normalize glycemic control are equally effective at all stages, such as primary prevention in normoalbuminuric patients, secondary prevention in microalbuminuria and macroalbuminuria, or tertiary prevention aimed at slowing or reversing further loss of GFR once impaired. Substantial randomized controlled trial data from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications exists to support postponement, but not outright prevention, of GFR loss in normoalbuminuric patients. Although secondary and tertiary prevention systematic studies are limited to methodologically insufficient insulin pump and transplantation trials, the reversal of advanced glomerular lesions observed in whole-pancreas transplant recipients who experienced long-term glycemic normalization offers convincing support for further research into glycemic interventions specifically for GFR preservation. In light of existing literature, we encourage the design of secondary and tertiary prevention trials that incorporate biomarker methods for identifying patients at highest risk of GFR loss because interventions to normalize hyperglycemia are resource-intensive and may be applied unnecessarily to clinical populations at low long-term GFR loss risk.