Glucose intolerance following chronic metabolic acidosis in man

The effect of chronic metabolic acidosis (0.1 g/(kg.day) x 3 days) on carbohydrate metabolism was examined with the glucose-clamp technique in 16 healthy volunteers. Hyperglycemic clamp. Plasma glucose concentration is acutely raised and maintained 125 mg/dl above the basal level. Because the glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism (M). Following NH₄Cl, M decreased from 8.95 ± 1.12 to 7.35 ± 0.76 (P < 0.05) despite an increased plasma insulin concentration (I) (23 ± 9%, P < 0.05). Consequently the M/I ratio, an index of tissue sensitivity to insulin, decreased by 32 ± 5% (P < 0.005). Euglycemic clamp. Plasma insulin concentration is acutely raised and maintained 101 ± 3 μU/ml above basal and plasma glucose is held constant at the fasting level by a variable glucose infusion (M). Following NH₄Cl both M and M/I decreased by 15 ± 4% (P = 0.005) and 15 ± 5% (P = 0.01), respectively. Metabolic acidosis had no effect on basal [3-³H]glucose production or the percent of decline (91 ± 4%) following hyperinsulinemia. Both hyperglycemic and euglycemic clamp studies indicate that impaired glucose metabolism following metabolic acidosis results from impaired tissue sensitivity to insulin.