Oral glucose tolerance, plasma insulin, and uric acid excretion in man during chronic administration of nicotinic acid

Abstract

The influence of antilipemic doses of nicotinic acid on carbohydrate tolerance, plasma insulin levels after oral glucose administration, serum uric acid levels, and renal excretion and clearance of uric acid was investigated in man. After a stabilization period of 1 wk, five subjects were given nicotinic acid, 1.5 g three times daily for 4 wk, under dietetically controlled conditions. Two of the subjects had normal oral glucose tolerance tests and the others, abnormal, prior to drug administration. Oral glucose (75 g) tolerance tests were performed twice prior to and weekly during drug administration and 1 wk after drug discontinuation. Twice weekly, throughout the 6 wk study, fasting plasma levels of uric acid, glucose, cholesterol, triglycerides, and immunoreactive insulin were determined. Insulin levels were also determined on each plasma sample during glucose tolerance tests. Rates of uric acid excretion were measured daily in two subjects. During drug administration, all subjects sustained increases, above predrug values, of plasma uric acid and of glucose after glucose tolerance tests. Glucosuria and ketonuria also ensued. Since plasma insulin levels increased along with glucose in nondiabetics, the data suggest that inhibition of insulin release is not the mechanism by which carbohydrate intolerance is produced or intensified. Renal excretion and clearance of uric acid decreased 50% and 75%, respectively; hence, the increases in plasma uric acid concentrations may be due, in whole or in part, to diminished renal clearance. Such diminished clearance may result from altered tubular handling of urate by keto acids and/or nicotinic acid and its metabolites.