NICOTINAMIDE EFFECTS ON GLUCOSE-METABOLISM IN SUBJECTS AT RISK FOR IDDM

Nicotinamide is being used in trials to prevent or delay the developme nt of clinical IDDM. A related compound, niacin, has been shown to cau se insulin resistance in normal subjects, resulting in increased insul in 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 an tibody-positive (ICA(+)) relatives of IDDM patients were given nicotin amide at a dose of 2 g/day for 2 weeks. Measurements of first-phase in sulin release, insulin sensitivity, glucose effectiveness, and the con stant for glucose disappearance (K-g) were measured at baseline, at th e end of 2 weeks of therapy, and after subjects had been off therapy f or at least 2 weeks. Nicotinamide administration caused a 23.6% decrea se in insulin sensitivity (P = 0.02). This decrease was associated wit h a fall in K-g 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 interve ntion trials using nicotinamide may be complicated by the changes in i nsulin secretion that are caused by the increased insulin resistance. Therefore, we strongly support the recommendation that at least one su bgroup of subjects enrolled in clinical trials to prevent IDDM have re gular measurements of both insulin sensitivity and insulin secretion p erformed. This subgroup should be randomly assigned and large enough f or statistical analysis to interpret properly the changes in insulin s ecretion that may occur.