Nicotinamide's effects on glucose metabolism in subjects at risk for IDDM

Nicotinamide is being used in trials to prevent or delay the development of clinical IDDM. A related compound, niacin, has been shown to cause insulin resistance in normal subjects, resulting in increased insulin secretion. This study was designed to answer the question: Does the short-term administration of nicotinamide cause insulin resistance in subjects who have a high risk of developing IDDM? Eight islet cell antibody-positive (ICA+) relatives of IDDM patients were given nicotinamide at a dose of 2 g/day for 2 weeks. Measurements of first-phase insulin release, insulin sensitivity, glucose effectiveness, and the constant for glucose disappearance (Kg) were measured at baseline, at the end of 2 weeks of therapy, and after subjects had been off therapy for at least 2 weeks. Nicotinamide administration caused a 23.6% decrease in insulin sensitivity (P = 0.02). This decrease was associated with a fall in Kg despite increased insulin secretion. Our data suggest that the use of nicotinamide in subjects who are at risk of developing IDDM may be complicated by the drug's effects on insulin sensitivity. By inducing insulin resistance, a therapeutic effect of nicotinamide on the diabetes disease process may be missed, and the interpretation of insulin secretion measurements that are obtained during the intervention trials using nicotinamide may be complicated by the changes in insulin secretion that are caused by the increased insulin resistance. Therefore, we strongly support the recommendation that at least one subgroup of subjects enrolled in clinical trials to prevent IDDM have regular measurements of both insulin sensitivity and insulin secretion performed. This subgroup should be randomly assigned and large enough for statistical analysis to interpret properly the changes in insulin secretion that may occur.