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Diabetes Spectrum 20:77-80, 2007
DOI: 10.2337/diaspect.20.2.77
© 2007 by the American Diabetes Association
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The Contribution of Medications to Hypoglycemia Unawareness

John R. White, Jr., PA, PharmD

The first 300 words of the full text of this article appear below.


    Introduction
 
Hypoglycemia unawareness is defined as the onset of neuroglycopenia before the appearance of autonomic warning symptoms.1 It is difficult to study in its natural form because of its paroxysmal and unpredictable nature; therefore, well-controlled trials are limited. However, much is known regarding risk factors, biochemical causes, and populations at greatest risk for the development of hypoglycemia unawareness. Less is known regarding the impact of medications on the development or recognition of this condition in patients with diabetes. Several medications are thought to worsen or promote hypoglycemia unawareness, whereas others may have an attenuating effect on the problem. This article will review hypoglycemia unawareness and summarize the effects of medications that may influence it.


    Hypoglycemic Counterregulation
 
In individuals without diabetes, a predictable, organized response occurs when blood glucose declines to hypoglycemic levels (Figure 1). First, insulin secretion is suppressed as glucose falls to < 81 mg/dl.1 The suppression of insulin secretion has two effects: peripheral glucose utilization is reduced and hepatic glucose output is induced. This action typically terminates the episode. However, if glucose decline continues to < 68 mg/dl, glucagon secretion from {alpha}-cells and epinephrine secretion from the adrenals are stimulated.1 These actions promote hepatic glucose production via gluconeogenesis and glycogenolysis. Growth hormone and cortisol are released as glucose levels decline even further (to ~ 63 mg/dl) but are probably best characterized as responders to prolonged hypoglycemia rather than acute responders. The central nervous system triggers autonomic symptoms of hypoglycemia at plasma glucose levels between 54 and 90 mg/dl (Table 1). These symptoms are aimed at encouraging consumption of calories and are the harbinger of impending neuroglycopenia. If unchecked, the hypoglycemia will cause neuroglycopenic symptoms (Table 1) and eventually seizures and coma.


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Figure 1. Glycemic threshold values for counterregulatory response to and physical consequences of insulin-induced hypoglycemia. Adapted from . . . [Full Text of this Article]

 

    Insulin
 

    β-Adrenergic Antagonists
 

    β-Adrenergic Agonists
 

    Methylxanthines
 

    Selective Serotonin Reuptake Inhibitors
 

    Conclusions
 

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Copyright © 2007 by the American Diabetes Association.