Hypoglycemia: From the Laboratory to the Clinic

Hypoglycemia remains a significant limitation to optimal treatment of diabetes with insulin and insulin secretagogues. Current research into the physiology of hypoglycemic counterregulation has helped us understand how to reduce risk of severe hypoglycemia, but much remains to be understood and exploited. In those with type 1 diabetes, risk for hypoglycemia is increased by the completeness of the insulin deficiency as well as the associated failure of glucagon responses to hypoglycemia and additional failure of other counterregulatory mechanisms created at least in part by repeated exposure to modest hypoglycemia itself. For those with long duration type 2 diabetes, hypoglycemia risk also increases with increasing insulin deficiency. Teaching patients to use insulin flexibly around changes in diet, exercise, alcohol ingestion, and other factors influencing insulin requirements and sensitivity can improve glycemic control while reducing hypoglycemia risk. Thereafter, increasing use of technology in both insulin delivery and, more recently, glucose sensing may be helpful. For the patient with truly intractable hypoglycemia, replacement of functional islet tissue by islet or organ transplantation is also a current therapeutic option. For the future, research into agents that may influence glucose sensing or cerebral and peripheral metabolism may offer new ways of enhancing defenses against hypoglycemia in the delivery of truly good glycemic control. © 2009 by the American Diabetes Association.