The Role of Hypoglycemia in Cardiovascular Outcomes in Diabetes.

Intensive glucose management, targeting lower glycated hemoglobin (A1C) levels, has been shown to reduce the microvascular complications of diabetes, but the effect on cardiovascular (CV) outcomes is less clear. Observational follow-up of intensive glucose management studies suggest possible long-term CV benefits, but no clear reduction in CV events has been seen over 3 to 5 years. Intensive glucose management also increases the risk for hypoglycemia, particularly in patients with longstanding diabetes, cognitive impairment and hypoglycemia unawareness. Severe hypoglycemia has been linked to adverse consequences, including cardiac dysrhythmias, CV events and death, but the precise role of hypoglycemia in CV outcomes is uncertain. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was terminated early because of a higher rate of CV events in the intensive arm. Post hoc analyses of ACCORD and other trials suggest that cardiac autonomic neuropathy may be a predisposing factor to CV events. The Analyses of the Action in Diabetes and Vascular Disease (ADVANCE) trial and the Veterans Affairs Diabetes Trial (VADT) showed that subjects with severe hypoglycemia had more frequent adverse outcomes. However, rather than causing adverse events, it appears that severe hypoglycemia may be a marker of vulnerability for such events. This review focuses on the current understanding of the association between hypoglycemia and CV risk.