Glycemic Variability: Both Sides of the Story

Abstract

### Case for a relationship between postprandial hyperglycemic variability and complication risk In both type 1 and type 2 diabetes, large prospective clinical studies have shown a strong relationship between time-averaged mean levels of glycemia as measured by HbA1c and diabetes complications (1). However, as reviewed elsewhere, in recent years several pieces of evidence have raised the possibility that glycemic instability may also contribute to the development of diabetes complications (2). Also reviewed elsewhere, in individuals with impaired glucose tolerance the degree of glycemia 2 h after a glucose challenge is a stronger predictor of cardiovascular disease than fasting glycemia (3). In subjects already known to have type 2 diabetes, postprandial glycemia can have the same deleterious effect on the likelihood of developing cardiovascular disease (4). Furthermore, these findings have been supported by pathophysiological evidence demonstrating that acute fluctuations in glycemia can produce significant alterations in normal homeostasis, such as those of endothelial dysfunction and increased inflammation (3). Taken together, these data begin to explain how acute increases in glycemia may influence the development of cardiovascular disease. However, the concept of glucose variability, even taking the above evidence into consideration, is more complex a phenomenon because it introduces the idea that multiple fluctuations of glycemia in the same individual could be more harmful than a simple episode of acute hyperglycemia or, indeed, chronic stable hyperglycemia. #### Clinical evidence in diabetes. An extensive evaluation of this concept has been done by Kilpatrick, Rigby, and Atkin (5), who first reported that glycemic instability is not a predictor of microvascular complications in patients from the Diabetes Control and Complications Trial (DCCT), in particular retinopathy, and then reported that mean daily glucose as well as pre- and postprandial hyperglycemia (PPG) predicted cardiovascular disease in the same cohort (6). Interestingly, the same author more recently reported that HbA1c instability, rather than that of glucose, is a predictor of microvascular …