Hypoglycemia-induced autonomic failure in IDDM is specific for stimulus of hypoglycemia and is not attributable to prior autonomic activation

C. Rattarasarn, Samuel Dagogo-Jack, J. J. Zachwieja, P. E. Cryer

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

We hypothesized, first, that recent antecedent hypoglycemia causes reduced autonomic responses to subsequent hypoglycemia in patients with well- controlled insulin-dependent diabetes mellitus (IDDM) and that the reduced responses are specific for the stimulus of hypoglycemia while the responses to other stimuli are unaltered and, second, that reduced autonomic responses, specifically sympathochromaffin, so-induced are not simply the result of prior activation of the system. To test the first hypothesis, eight patients with IDDM, selected for HbA(1c) levels <8.0% and the absence of classic diabetic autonomic neuropathy, were studied twice. On one occasion, clamped hypoglycemia (~2.8 mM) was produced at 1400-1600 on days 2 and 3; on the other occasion clamped euglycemia (~5.6 mM) was produced at those times. On both occasions, autonomic responses to hypoglycemia (~2.8 mM) were determined the morning of day 3 and those to standing, exercise, and a formula meal the morning of day 4. Following afternoon hypoglycemia, 1) the adrenomedullary epinephrine (EPI) response to hypoglycemia was reduced (P = 0.0397) but that to standing, exercise, and a meal were unaltered; 2) the sympathetic neural norepinephrine (NE) response to standing and to exercise was unaltered; and 3) the partially parasympathetic neural-mediated pancreatic polypeptide response to a meal was unaltered. To test the second hypothesis, seven nondiabetic subjects were studied twice, once with cycle exercise (60% peak V̇O2 x 60 min) and once without exercise 90 min before clamped hypoglycemia (~2.8 mM). Prior exercise had no effect on the EPI, NE, or pancreatic polypeptide responses to hypoglycemia. We conclude, first, that the phenomenon of hypoglycemia-associated autonomic failure can be induced in patients with well-controlled IDDM and is specific for the stimulus of hypoglycemia and, second, that this is not simply the result of prior activation of the system.

Original languageEnglish (US)
Pages (from-to)809-818
Number of pages10
JournalDiabetes
Volume43
Issue number6
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Type 1 Diabetes Mellitus
Hypoglycemia
Exercise
Pancreatic Polypeptide
Epinephrine
Meals
Norepinephrine
Breakfast
Diabetic Neuropathies

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hypoglycemia-induced autonomic failure in IDDM is specific for stimulus of hypoglycemia and is not attributable to prior autonomic activation. / Rattarasarn, C.; Dagogo-Jack, Samuel; Zachwieja, J. J.; Cryer, P. E.

In: Diabetes, Vol. 43, No. 6, 01.01.1994, p. 809-818.

Research output: Contribution to journalArticle

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abstract = "We hypothesized, first, that recent antecedent hypoglycemia causes reduced autonomic responses to subsequent hypoglycemia in patients with well- controlled insulin-dependent diabetes mellitus (IDDM) and that the reduced responses are specific for the stimulus of hypoglycemia while the responses to other stimuli are unaltered and, second, that reduced autonomic responses, specifically sympathochromaffin, so-induced are not simply the result of prior activation of the system. To test the first hypothesis, eight patients with IDDM, selected for HbA(1c) levels <8.0{\%} and the absence of classic diabetic autonomic neuropathy, were studied twice. On one occasion, clamped hypoglycemia (~2.8 mM) was produced at 1400-1600 on days 2 and 3; on the other occasion clamped euglycemia (~5.6 mM) was produced at those times. On both occasions, autonomic responses to hypoglycemia (~2.8 mM) were determined the morning of day 3 and those to standing, exercise, and a formula meal the morning of day 4. Following afternoon hypoglycemia, 1) the adrenomedullary epinephrine (EPI) response to hypoglycemia was reduced (P = 0.0397) but that to standing, exercise, and a meal were unaltered; 2) the sympathetic neural norepinephrine (NE) response to standing and to exercise was unaltered; and 3) the partially parasympathetic neural-mediated pancreatic polypeptide response to a meal was unaltered. To test the second hypothesis, seven nondiabetic subjects were studied twice, once with cycle exercise (60{\%} peak V̇O2 x 60 min) and once without exercise 90 min before clamped hypoglycemia (~2.8 mM). Prior exercise had no effect on the EPI, NE, or pancreatic polypeptide responses to hypoglycemia. We conclude, first, that the phenomenon of hypoglycemia-associated autonomic failure can be induced in patients with well-controlled IDDM and is specific for the stimulus of hypoglycemia and, second, that this is not simply the result of prior activation of the system.",
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