We read with interest the article by Kilpatrick et al. (1) and the accompanying editorial by Bolli (2). While the analysis of seven-point glucose profiles reported in this study (1) suggested that glucose variability is not an independent risk factor for microvascular complications, the seven-point profile may not be an accurate representation of true glycemic variability as measured by continuous blood glucose monitoring (3). Although there are not enough data at present to justify new treatment guidelines based on glycemic variability, there certainly are important published data (3) showing that glycemic variability leads to greater oxidative stress. Since increased intracellular superoxide production has been shown to initiate a large number of hyperglycemia-induced mechanisms related to the pathogenesis of diabetic complications (4), we believe that further investigation of the hypothesis that increased glycemic variability is a risk factor for diabetic complications is warranted.
Indeed, it was not that long ago that there was widespread doubt in the medical community that increased levels of hyperglycemia were a risk factor for diabetic complications (5). However, this doubt was addressed by further clinical research (6).
A little-noticed but very important observation published (6) by the Diabetes Control and Complications Trial Research Group >10 years ago was that subgroups of patients receiving more physiologic insulin replacement had a significantly less risk of retinopathy than subgroups having the identical A1C levels for the entire study but were treated with insulin less frequently. In light of these observations, we feel that it is scientifically unwarranted to conclude that “increasing the number of daily injections of insulin or moving to continuous subcutaneous insulin infusion in place of multiple daily injections might not be necessary if the current treatment results in A1C consistently <7.0% over time” (2).
Rather, given the potential harm that would result if in fact glycemic variability turns out to be a significant risk factor for diabetes complications, we advocate resolving this important issue by conducting randomized clinical trials. Given their well-deserved place in the pantheon of diabetes physician and scientists, we are certain that the Kilpatrick et al. and Bolli would all agree.
