Antecedent hypoglycemia of 3.9 mmol/l and 3.3 mmol/l produced a hierarchy of significantly blunted counterregulatory responses to subsequent hypoglycemia in healthy men (P<0.01).
RCT (n=8)
Crossover
p-value: p=<0.01
The aim of the study was to determine the effects of specific levels of antecedent hypoglycemia on subsequent autonomic, neuroendocrine, and metabolic counterregulatory responses. Eight healthy, overnight-fasted male subjects were studied during 2-day protocols on four separate randomized occasions separated by at least 2 months. On day 1, insulin was infused at a rate of 9 pmol x kg(-1) x min(-1) and 2-h clamped euglycemia (plasma glucose 5.2 +/- 0.2 mmol/l) or differing hypoglycemia (plasma glucose 3.9 +/- 0.1, 3.3 +/- 0.1, or 2.9 +/- 0.1 mmol/l) was obtained during morning and afternoon. The next morning after an evening meal and 10-h overnight fast, each subject underwent a 2-h hyperinsulinemic (9 pmol x kg(-1) x min-1) hypoglycemic (2.9 +/- 0.1 mmol/l) clamp study. Despite equivalent day 2 plasma glucose and insulin levels, differing levels of antecedent hypoglycemia produced specific blunting of subsequent counterregulatory responses. Day 1 hypoglycemia of 3.9 mmol/l resulted in significantly (P < 0.01) blunted epinephrine, muscle sympathetic nerve activity, and glucagon responses. Day 1 hypoglycemia of 3.3 mmol/l resulted in additional significant blunting (P < 0.01) of pancreatic polypeptide, norepinephrine, growth hormone, endogenous glucose production, and lipolytic responses. Deeper day 1 hypoglycemia of 2.9 mmol/l produced similar day 2 counterregulatory failure as day 1 hypoglycemia of 3.3 mmol/l. In summary, in healthy overnight-fasted men, mild antecedent hypoglycemia of 3.9 mmol/l significantly blunts sympathoadrenal and glucagon, but not other forms of neuroendocrine counterregulatory responses, to subsequent hypoglycemia. Antecedent hypoglycemia of 3.3 mmol/l resulted in additional significant blunting of all major neuroendocrine and metabolic responses to subsequent hypoglycemia. We conclude that in normal humans, there is a hierarchy of blunted counterregulatory responses that are determined by the depth of antecedent hypoglycemia.
Davis et al. (Fri,) conducted a rct in Healthy volunteers (n=8). Antecedent hypoglycemia vs. Antecedent euglycemia (plasma glucose 5.2 mmol/l) was evaluated on Autonomic, neuroendocrine, and metabolic counterregulatory responses to subsequent hypoglycemia (p=<0.01). Antecedent hypoglycemia of 3.9 mmol/l and 3.3 mmol/l produced a hierarchy of significantly blunted counterregulatory responses to subsequent hypoglycemia in healthy men (P<0.01).
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