Iatrogenic hypoglycemia is the limiting factor in the management of insulin-dependent diabetes mellitus (IDDM). It causes recurrent physical morbidity, some mortality, and recurrent or even persistent psychosocial morbidity. The principles of glucose counterregulation, the physiological mechanisms that normally very effectively prevent or correct hypoglycemia, are now known. Decrements in insulin, increments in glucagon, and, in the absence of the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors. Iatrogenic hypoglycemia in IDDM is the result of the interplay of absolute or relative therapeutic insulin excess and compromised glucose counterregulation. Syndromes of compromised glucose counterregulation include defective glucose counterregulation (the result of combined deficiencies of the glucagon and epinephrine responses to falling glucose levels), hypoglycemia unawareness (loss of the warning, neurogenic symptoms of developing hypoglycemia), and elevated glycemic thresholds (lower glucose levels required) for autonomic activation and symptoms during effective intensive therapy. These have been conceptualized as examples of hypoglycemiaassociated autonomic failure, a functional disorder distinct from classical diabetic autonomic neuropathy, in IDDM. Recent antecedent iatrogenic hypoglycemia appears to be a major factor in the pathogenesis of hypoglycemia unawareness; there is increasing evidence that this syndrome is reversible with scrupulous avoidance of hypoglycemia. It probably also contributes substantially to the syndrome of elevated glycemic thresholds during intensive therapy. However, factors in addition to recent antecedent hypoglycemia play an important role in the pathogenesis of the syndrome of defective glucose counterregulation. Pending the prevention and cure of IDDM, we need to learn to replace insulin in a much more physiological fashion and/or to prevent, correct, or compensate for compromised glucose counterregulation if we are to eliminate hypoglycemia from the lives of people with IDDM without compromising glycemic control. In the meantime, we must continue to seek better insight into the fundamental mechanisms of compromised glucose counterregulation and to develop practical preventive clinical strategies and practice hypoglycemia risk factor reduction with our patients.
Skip Nav Destination
Banting Lecture| November 01 1994
Hypoglycemia: The Limiting Factor in the Management of IDDM
Philip E Cryer
Philip E Cryer
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and the General Clinical Research Center and Diabetes Research and Training Center, Washington University School of Medicine
St. Louis, Missouri
Search for other works by this author on:
Address correspondence and reprint requests to Dr. Philip E. Cryer, Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine (Box 8127), 660 South Euclid Ave., St. Louis, MO 63110.
Philip E Cryer; Hypoglycemia: The Limiting Factor in the Management of IDDM. Diabetes 1 November 1994; 43 (11): 1378–1389. https://doi.org/10.2337/diab.43.11.1378
Download citation file: