Effects of Phosphate Deprivation on Carbohydrate Metabolism

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Abstract
In primary hyperparathyroidism, hyperinsulinemia and endogenous insulin resistance may relate to depressed serum and total body inorganic phosphate. In the present study 10 healthy adults received intravenous challenge tests while on a nutritious, isocaloric liquid formula and again after 10-14 days of the same diet devoid of phosphate. During this latter period total body phosphate loss has previously been shown to average 1.5 mmol/kg body weight. The serum phosphate fell significantly from 1.30 ± .04 mM to 1.03 ± .07 mM (p <0.01) with no change in serum calcium concentration. Phosphate deprivation did not alter basal glucose or insulin concentrations. However, 25-65% increases of plasma insulin increments at 5, 10 and 20 minutes after an i.v. glucose bolus (25 grams) were observed (p <0.05) without change in plasma glucose curves. Moreover, total plasma insulin responses to i.v. glucose were 30% greater during the period of phosphate deprivation (p <0.05). Intravenous tolbutamide (1 g) produced no changes in glucose responses and failed to elicit hyperinsulinemia. We conclude that short term phosphate deprivation reproduces the exaggerated plasma insulin response to i.v. glucose that is observed in primary hyperparathyroidism and may contribute to endogenous insulin resistance found in this condition. 1 This project was supported by Research Grant AM 10305 and Clinical Research Center Grant RR 00058 from the United States Public Health Service, Bethesda, Maryland, and by TOPS Club, Inc., Obesity and Metabolic Research Program, Milwaukee, Wisconsin, U.S.A.