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Original Articles

Mechanism of Awareness of Hypoglycemia: Perception of Neurogenic (Predominantly Cholinergic) Rather Than Neuroglycopenic Symptoms

  1. Dwight A Towler,
  2. Carolyn E Havlin,
  3. Suzanne Craft and
  4. Philip Cryer
  1. Division of Endocrinology, Diabetes, and Metabolism of the Department of Medicine; and the General Clinical Research Center; and the Diabetes Research and Training Center, Washington University School of Medicine St. Louis, Missouri
  1. Address correspondence and reprint requests to Dr. Philip E. Cryer, Division of Endocrinology, Diabetes, and Metabolism (Box 8127), Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110
Diabetes 1993 Dec; 42(12): 1791-1798. https://doi.org/10.2337/diab.42.12.1791
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Abstract

We sought 1) to determine which symptoms of hypoglycemia are reproducible, 2) to pharmacologically distinguish neurogenic (autonomic) from neuroglycopenic symptoms, and 3) to test the hypothesis that awareness of hypoglycemia is the result of perception of neurogenic rather than neuroglycopenic symptoms. Awareness of hypoglycemia and 19 symptoms were quantitated in 10 normal, young adults, each studied on four occasions in random sequence, during 1) clamped euglycemia (∼ 5 mM), 2) clamped hypoglycemia (∼ 2.5 mM), 3) clamped hypoglycemia with combined α- and β-adrenergic blockade (phentolamine and propranolol), and 4) clamped hypoglycemia with pan-autonomic blockade (phentolamine, propranolol and atropine). Significant (ANOVA, P < 0.001) treatment effects on the awareness of hypoglycemia (“blood sugar low”) were noted. No change occurred in the score for this during euglycemia, but the mean ± SE increase was 2.1 ± 0.4 during hypoglycemia. This increase was not reduced significantly by adrenergic blockade (1.6 ± 0.5), but was reduced significantly and substantially (∼ 70%) by pan-autonomic blockade (0.6 ± 0.3). Significant neurogenic symptoms included shaky/tremulous (P < 0.001), heart pounding (P < 0.001), and nervous/anxious (P = 0.002), all adrenergic; and sweaty (P < 0.001), hungry (P < 0.001), and tingling (P = 0.009), all cholinergic. Significant neuroglycopenic symptoms, those produced by hypoglycemia but not reduced by pan-autonomic blockade, included warm (P < 0.001), weak (P = 0.011), difficulty thinking/confused (P = 0.004), and tired/drowsy (P = 0.003). We conclude that muscarinic cholinergic mechanisms mediate an important and previously uncharacterized component of the neurogenic symptoms of hypoglycemia and awareness of hypoglycemia. Awareness of hypoglycemia is largely, perhaps exclusively, the result of perception of neurogenic rather than neuroglycopenic symptoms.

  • Received May 12, 1993.
  • Revision received July 26, 1993.
  • Accepted July 26, 1993.
  • Copyright © 1993 by the American Diabetes Association
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December 1993, 42(12)
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Mechanism of Awareness of Hypoglycemia: Perception of Neurogenic (Predominantly Cholinergic) Rather Than Neuroglycopenic Symptoms
Dwight A Towler, Carolyn E Havlin, Suzanne Craft, Philip Cryer
Diabetes Dec 1993, 42 (12) 1791-1798; DOI: 10.2337/diab.42.12.1791

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Mechanism of Awareness of Hypoglycemia: Perception of Neurogenic (Predominantly Cholinergic) Rather Than Neuroglycopenic Symptoms
Dwight A Towler, Carolyn E Havlin, Suzanne Craft, Philip Cryer
Diabetes Dec 1993, 42 (12) 1791-1798; DOI: 10.2337/diab.42.12.1791
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