Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It Does!

There is no argument that improving mean levels of glycemic control as judged by assays for glycated hemoglobin (HbA(1c)) reduces the risks of microvascular complications and cardiovascular disease events in patients with type 1 and type 2 diabetes. However, observations in some trials have suggested that targeting HbA(1c) to suggested targets may not always result in improved outcomes for people with long-standing type 2 diabetes. The reasons why the glycemic control strategies that primarily use HbA(1c) in these studies did not have predicted outcomes are not clear. Thus, controversy remains as to whether there are glycemic metrics beyond HbA(1c) that can be defined as effective measures that can be used in addition to HbA(1c) to help in assessing the risk of an individual developing diabetes complications. In this regard, the concept of "glycemic variability" (GV) is one metric that has attracted a lot of attention. GV can be simply defined as the degree to which a patient's blood glucose level fluctuates between high (peaks) and low (nadir) levels. The best and most precise way to assess GV is also one that is still debated. Thus, while there is universal agreement that HbA(1c) is the current gold standard for the primary clinical target, there is no consensus as to whether other proposed glycemic metrics hold promise to provide additional clinical data or whether there should be additional targets beyond HbA(1c). Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative below, Dr. Hirsch provides his argument that fluctuations in blood glucose as assessed by GV metrics are deleterious and control of GV should be a primary treatment target. In the following counterpoint narrative, Dr. Bergenstal argues that there are better markers to assess the risk of diabetes than GV and provides his consideration of other concepts.