Glucose Variability and Diabetic Complications: Is It Time to Treat?
Antonio Ceriello
Abstract
Increasing evidence is supporting the role of glucose variability (GV) in the development of diabetic complications, particularly cardiovascular (CV) ones (1). Many observational studies (1) and post hoc analyses of trials, such as ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) (2), DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events) (3), VADT (Veterans Affairs Diabetes Trial) (4), ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) (5), and EMPAREG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) (6), confirm that in type 2 diabetes long-term GV, in terms of fasting glucose and/or HbA1c variability, is correlated with an increased risk of both CV and microvascular complications. In this issue of Diabetes Care , a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial adds a further important piece of evidence on this topic (7). This analysis shows that HbA1c variability is a strong predictor of the total mortality in people with type 2 diabetes and a previous CV event or high risk for CV disease (7). It is worth mentioning that, with abundant measurements in the ACCORD trial, it has been possible for the first time to compare GV effects between the standard and intensive treatment arms. As is well known, increased mortality from all causes was reported in the intensive treatment arm of ACCORD, leading to the premature discontinuation of the study (8). In this post hoc analysis it emerges that HbA1c variability, together with a higher mean HbA1c level, is involved in the increased total mortality, particularly in the intensive treatment arm (7). The authors suggest …