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

Abstract

There is no argument that improving mean levels of glycemic control as judged by assays for glycated hemoglobin (HbA1c) 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 HbA1c 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 HbA1c in these studies did not have predicted outcomes are not clear. Thus, controversy remains as to whether there are glycemic metrics beyond HbA1c that can be defined as effective measures that can be used in addition to HbA1c 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 HbA1c 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 HbA1c. 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. —William T. Cefalu Editor in Chief, Diabetes Care

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Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

“…Landmark clinical trials have shown that lowering HbA1c reduces the risk of development and progression of diabetes complications,1, 2 which has led to a treatment focus on achieving the generally recommended target HbA1c of <7.0% 3. Although controversial,4, 5 in the past decade, a body of evidence has implicated glycaemic variability in the pathogenesis of diabetes complications, suggesting that glycaemic variability should also be considered a target for glucose‐lowering therapies 6, 7. Glycaemic variability refers to acute excursions in blood glucose levels, including hypoglycaemic events and postprandial hyperglycaemia, and may be known by some patients and physicians as daily glucose fluctuations 8.…”

Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk

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