Should minimal blood glucose variability become the gold standard of glycemic control?

The Diabetes Complications and Control Trial (DCCT) established glycosylated hemoglobin (A1C) as the gold standard of glycemic control, with levels </=7% deemed appropriate for reducing the risk of vascular complications. Yet, even when A1Cs were comparable between intensively treated subjects and their conventionally treated counterparts, the latter group experienced a markedly higher risk of progression to retinopathy over time. Our speculative explanation, based on the discovery that hyperglycemia-induced oxidative stress is the chief underlying mechanism of glucose-mediated vascular damage, was that glycemic excursions were of greater frequency and magnitude among conventionally treated patients, who received fewer insulin injections. Subsequent studies correlating the magnitude of oxidative stress with fluctuating levels of glycemia support the hypothesis that glucose variability, considered in combination with A1C, may be a more reliable indicator of blood glucose control and the risk for long-term complications than mean A1C alone.