Defining and Reporting Hypoglycemia in Diabetes

I atrogenic hypoglycemia causes recurrent morbidity in most people with type 1 diabetes and in many with type 2 diabetes and is sometimes fatal. It also impairs defenses against subsequent hypoglycemia. Furthermore, the barrier of hypoglycemia precludes maintenance of euglycemia over a lifetime of diabetes; thus, full realization of the benefits of glycemic control is rarely achieved. Therefore, hypoglycemia is the critical limiting factor in the glycemic management of diabetes in both the short and long term (1). Clinicians have recognized the problem of iatrogenic hypoglycemia since the first use of insulin in 1922 (2). The problem was underscored 70 years later by the finding that intensive glycemic therapy both decreased the frequency of longterm complications and increased the frequency of hypoglycemia in the Diabetes Control and Complications Trial (DCCT) (3,4). Despite steady improvements in the glycemic management of diabetes, and perhaps because of the impetus for glycemic control that resulted from the DCCT (3,4) and the U.K. Prospective Diabetes Study (5,6), recent population-based data indicate that hypoglycemia continues to be a major problem for people with both type 1 and type 2 diabetes (7–9). The ultimate goal of the glycemic management of diabetes is a lifetime of euglycemia without hypoglycemia. That will undoubtedly require glucoseregulated insulin replacement or secretion (10). Pending that, the goal of new drugs, devices, or management strategies to be used for the glycemic management of diabetes is to both improve glycemic control and reduce the frequency and severity of hypoglycemia. How should new drugs, devices, or strategies be evaluated and reported from the perspective of hypoglycemia? The American Diabetes Association assembled a Workgroup on Hypoglycemia in June of 2004 to discuss that issue and, in part, to advise the U.S. Food and Drug Administration as to how hypoglycemia should be used as an end point in studies of new treatments for diabetes. After reviewing the background of hypoglycemia in diabetes, the Workgroup discussed three questions: 1) How should hypoglycemia be defined? 2) How should hypoglycemia be reported? 3) What constitutes a meaningful reduction in hypoglycemia?