Hypoglycemia is the limiting factor in the management of diabetes

Hypoglycemia is the limiting factor, both conceptually and in practice, in the management of diabetes mellitus. While the long-term goal of diabetes research must remain the cure and the prevention of the disease and reasonable near-term goals might include perfect insulin replacement or prevention of complications despite ongoing hyperglycemia, the most pressing short-term goal for people with diabetes would seem to be insight leading to strategies that effectively minimize the risk of hypoglycemia and thus permit low-risk glycemic control. Having reviewed the field in detail recently, the author offers his personal views of the key questions - concerning the physiology of glucose counterregulation, its pathophysiology in diabetes, and hypoglycemia in diabetes - that, if answered, might lead to a reduced risk of iatrogenic hypoglycemia in people with diabetes. The overriding question is: How can we learn to replace insulin more perfectly, prevent, correct or compensate for compromised glucose counterregulation, or both?