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Severe iatrogenic hypoglycemia in type 2 diabetes mellitus

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 4–5 (2007)Cite this article

Decreased insulin levels are normally the first defense against hypoglycemia, whereas increased glucagon levels are the second defense. Increases in epinephrine levels, the third defense, become critical when glucagon is deficient. The sympathoadrenal response causes the characteristic symptoms of hypoglycemia, and thereby prompts the behavioral defense to glucose deficit—ingestion of food. All of these defenses are compromised in type 1 diabetes mellitus (T1DM) and advanced (insulin-deficient) type 2 diabetes mellitus (T2DM): insulin levels do not decrease, glucagon levels do not increase, and the increase in epinephrine levels is often attenuated.1,2 Iatrogenic hypoglycemia, therefore, results from the interplay of absolute or relative therapeutic insulin excess and compromised physiologic and behavioral defenses against a fall in plasma glucose concentrations.1,2

Iatrogenic hypoglycemia is the limiting factor in the glycemic management of both T1DM and T2DM. This potentially life-threatening complication of therapy causes recurrent morbidity in most patients with T1DM and many of those with T2DM. Hypoglycemia also precludes maintenance of euglycemia over a lifetime of diabetes and, thus, full realization of the vascular benefits of long-term glycemic control. In addition, even asymptomatic episodes of hypoglycemia compromise defenses against subsequent episodes by causing hypoglycemia-associated autonomic failure (HAAF), which leads to a vicious cycle of recurrent hypoglycemia.1,2

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Acknowledgements

PE Cryer's cited work was supported, in part, by US Public Health Service/NIH grants R37 DK27085, M01 R00036, P60 DK20579 and T32 DK07120, and a postdoctoral fellowship award from the American Diabetes Association.

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  1. Campus Box 8127, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63109, USA pcryer@wustl.edu

Authors and Affiliations

  1. PE Cryer is the Irene E and Michael M Karl Professor of Endocrinology and Metabolism in Medicine at Washington University School of Medicine, St Louis, MO, USA.,

    Philip E Cryer

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The author has served as a member of the Advisory Boards of MannKind Corporation, Novo Nordisk and Takeda Pharmaceuticals North America.

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Cryer, P. Severe iatrogenic hypoglycemia in type 2 diabetes mellitus. Nat Rev Endocrinol 3, 4–5 (2007). https://doi.org/10.1038/ncpendmet0355

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