Proinflammatory and Prothrombotic Effects of Hypoglycemia

Hypoglycemia is known to be intrinsic to the treatment of diabetes because insulin is a powerful glucose-lowering agent and sulfonylureas exert their effect through insulin release by the pancreatic β-cells. Hypoglycemia occurs in association with these two common modes of therapy and was previously accepted as a part of the treatment of this condition. With the arrival of other modes of diabetes treatment, such as metformin, thiazolidenediones, α2-glucosidase inhibitors, and incretins, which do not induce hypoglycemia except when administered in combination with insulin and sulfonylureas, the issue of hypoglycemia has to be assessed in the context of both the immediate risk related to neuroglycopenia and the possible long-term risk of diabetic vascular complications. Vascular complications of hypoglycemia have to be tackled with greater urgency now because two recent trials of intensified diabetes treatment with insulin, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and Veteran's Affairs Diabetes Trial (VADT), did not demonstrate a reduction in cardiovascular events (1,2). In fact, the intensified insulin treatment arm of the ACCORD trial had to be halted because of an increase in overall mortality, despite a reduction in acute myocardial infarction. The rate of hypoglycemia in both trials was significantly increased with intensified insulin treatment. Although the analysis of the ACCORD data did not support the hypothesis that the increased mortality in the study was a result of hypoglycemia, the fact that hypoglycemia may often be asymptomatic leaves us with the possibility that it may be responsible. The fact that hypoglycemia results in platelet hyperaggregability (3) and an increase in several factors involved …