Impact of Glycemic Variability on Cardiovascular Risk in Diabetes

A growing body of evidences indicates the role of increased glucose variability (GV) as an independent cardiovascular risk factor in diabetes. It has been shown that high GV is associated with coronary and carotid atherosclerosis in diabetic subjects. The impact of enhanced glycemic fluctuations on vascular wall is mediated through non-enzymatic glycation, oxidative stress, activation of inflammatory pathways, and endothelial dysfunction. Thus, the effects of high GV exacerbate the influence of chronic hyperglycemia. The FinnDiane study established existence of a relationship between glycated hemoglobin (HbA1c) variability and cardiovascular events (myocardial infarction, coronary artery procedure including by-pass surgery or angioplasty, stroke, limb amputation because of ischemia, or a peripheral artery procedure) in patients with type 1 diabetes. In ADVANCE study visit-to-visit HbA1c and fasting glucose variability was associated with cardiovascular events in type 2 diabetic subjects; moreover, HbA1c variability was associated with all-cause mortality. In Verona Diabetes Study, fasting GV was predictor of cardiovascular mortality in elderly patients with type 2 diabetes. In-hospital glycemic excursions in patients with acute myocardial infarction and in diabetic patients undergoing percutaneous coronary intervention predict the risk of adverse cardiac events. The episodes of hypoglycemia in diabetic patients with high GV may contribute to an increased risk of arrhythmias, myocardial ischemia and infarction, and stroke. The data presented give support to notion that GV could be considered a new therapeutic target in patients with diabetes and cardiovascular disease.