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.
Original Articles|
December 01 1993
Mechanism of Awareness of Hypoglycemia: Perception of Neurogenic (Predominantly Cholinergic) Rather Than Neuroglycopenic Symptoms
Dwight A Towler;
Dwight A Towler
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
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Carolyn E Havlin;
Carolyn E Havlin
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
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Suzanne Craft;
Suzanne Craft
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
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Philip Cryer
Philip Cryer
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
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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;42(12):1791–1798
Article history
Received:
May 12 1993
Revision Received:
July 26 1993
Accepted:
July 26 1993
PubMed:
8243825
Citation
Dwight A Towler, Carolyn E Havlin, Suzanne Craft, Philip Cryer; Mechanism of Awareness of Hypoglycemia: Perception of Neurogenic (Predominantly Cholinergic) Rather Than Neuroglycopenic Symptoms. Diabetes 1 December 1993; 42 (12): 1791–1798. https://doi.org/10.2337/diab.42.12.1791
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