MECHANISM OF AWARENESS OF HYPOGLYCEMIA - PERCEPTION OF NEUROGENIC (PREDOMINANTLY CHOLINERGIC) RATHER THAN NEUROGLYCOPENIC SYMPTOMS

We sought 1) to determine which symptoms of hypopglycemia are reproduc ible, 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 w ere quantitated in 10 normal, young adults, each studied on four occas ions in random sequence, during 1) clamped euglycemia (approximately 5 mM), 2) clamped hypoglycemia (approximately 2.5 mM), 3) clamped hypog lycemia with combined alpha- and beta-adrenergic blockade (phentolamin e and propanolol), and 4) clamped hypoglycemia with panautonomic block ade (phentolamine, propranolol and atropine). Significant (ANOVA, P < 0.001) treatment effects on the awareness of hypoglycemia (''blood sug ar low'') were noted. No change occurred in the score for this during euglycemia, with the mean +/- SE increase was 2.1 +/- 0.4 during hypog lycemia. This increase was not reduced significantly by adrenergic blo ckade (1.6 +/- 0.5), but was reduced significantly and substantially ( approximately 70%) by panautonomic blockade (0.6 +/- 0.3). Significant neurogenic symptoms included shaky/tremulous (P < 0.001), heart pound ing (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 h ypoglycemia but not reduced by panautonomic blockade, included warm (P < 0.001), week (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 compon ent of the neurogenic symptoms of hypoglycemia and awareness of hypogl ycemia. Awareness of hypoglycemia is largely, perhaps exclusively, the result of perception of neurogenic rather than neuroglycopenic sympto ms.