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Hypoglycemia is known to decrease the body temperature and to stimulate counterregulatory hormone secretion. Although it is well established that antecedent hypoglycemia reduces the hormonal response to subsequent hypoglycemia, the effects of antecedent hypoglycemia on the subsequent hypothermic response are obscure. In the present study, body temperature was measured orally during a total of 90 glucose clamp experiments in 45 healthy men. The clamps lasted 6 hours and were performed under 6 different experimental conditions: a euglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg x min (low insulin-eu), a euglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg x min (high insulin-eu), a hypoglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg x min (low insulin-hypo), a hypoglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg x min (high insulin-hypo), and 2 hypoglycemic clamps following an antecedent 2.5-hour hypoglycemia (56 mg/dL) induced by either a low (1.5 mU/kg x min, low insulin-ante-hypo) or a high (15.0 mU/kg x min, high insulin-ante-hypo) rate of insulin infusion. Plasma glucose was maintained normal during the euglycemic clamps and was decreased stepwise during the hypoglycemic clamps (76 --> 66 --> 56 --> 46 mg/dL). During the hypoglycemic clamps, body temperature decreased by 0.26 degrees +/- 0.09 degrees C in low insulin-hypo, 0.28 degrees +/- 0.09 degrees C in high insulin-hypo, 0.29 degrees +/- 0.09 degrees C in low insulin-ante-hypo, and 0.41 + 0.11 degrees C in high insulin-ante-hypo (all P < .01). There were no differences in the hypothermic response to hypoglycemia among the different hypoglycemic conditions (P > .1 for all comparisons). In contrast, body temperature remained unchanged during the euglycemic clamps, so the changes in body temperature differed significantly during the euglycemic clamps versus the hypoglycemic clamps (P < .05 for all comparisons). The data show that the body temperature decreases during hypoglycemia and this decrease is influenced neither by antecedent hypoglycemia nor by circulating insulin levels.