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Effects of oral carbohydrate on autonomic nervous system counterregulatory responses during hyperinsulinemic hypoglycemia and euglycemia

¹Department of Medicine, Vanderbilt University Medical Center and ²Veterans Affairs, Nashville, Tennessee

Submitted 28 May 2008 ; accepted in final form 30 June 2008

The effects of oral carbohydrate on modulating counterregulatory responses in humans remain undecided. This study's specific aim was to determine the effects of oral carbohydrate on autonomic nervous system (ANS) and neuroendocrine responses during hyperinsulinemic hypoglycemia and euglycemia. Nineteen healthy volunteers were studied during paired, single blind experiments. Nine subjects underwent two-step glucose clamps consisting of 60 min of euglycemia (5.0 mmol/l) followed by either 15 g of oral carbohydrate (cal) as orange juice or a noncaloric control (nocal) and subsequent 90 min of clamped hypoglycemia (2.9 mmol/l). Ten other subjects underwent two randomized 150-min hyperinsulinemic-euglycemic clamps with cal or nocal control administered at 60 min. Oral carbohydrate initially blunted (P < 0.05) epinephrine, norepinephrine, cortisol, glucagon, pancreatic polypeptide, muscle sympathetic nerve activity (MSNA), symptom, and systolic blood pressure responses during hypoglycemia. However, by the end of 90 min of hypoglycemia, plasma epinephrine and norepinephrine responses had rebounded and were increased (P < 0.05) compared with control. MSNA and cortisol levels remained suppressed during hypoglycemia (P < 0.05) after cal, whereas pancreatic polypeptide, glucagon, symptom, and blood pressure responses increased similar to control following initial suppression. Oral carbohydrate had no effects on neuroendocrine or ANS responses during hyperinsulinemic euglycemia. These results demonstrate that oral carbohydrate can have differential effects on the time course of ANS and neuroendocrine responses during hypoglycemia. We conclude that gastro-splanchnic-portal sensing of an amount of carbohydrate recommended for use in clinical practice for correction of hypoglycemia can have widespread and significant effects on central nervous system mediated counterregulatory responses in healthy humans.

hypoglycemia; euglycemia; hyperinsulinemia; humans; oral carbohydrate

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