Acceleration of the development of diabetes in obese diabetic (db/db) mice by nicotinamide: a comparison with its antidiabetic effects in non-obese diabetic mice.

Destruction of pancreatic beta cells has been implicted in the progression to hyperglycemia in type 1 diabetes. While there is evidence of beta-cell loss in type 2 diabetes, its contribution to the development of the diabetic state is undecided. Nicotinamide has defensive effects against toxic insults to the pancreatic islets and confers protection in both human and animal models of type 1 diabetes, but its effects on type 2 diabetes are less well documented. This report describes a comparison of the outcome of chronic oral administration of nicotinamide on the development of diabetes in obese diabetic (db/db) and non-obese diabetic (NOD) mice models of type 2 and type 1 diabetes, respectively. Nicotinamide was administered in the diet (5 g/kg diet) for 12 (db/db) or 24 (NOD) weeks. Over the 12 weeks of the study, control diabetic (db/db) mice became progressively more hyperglycemic and glycosuric, while serum and pancreatic insulin levels decreased compared with those on day 0. In mice treated with nicotinamide, there was a pronounced acceleration in the development of hyperglycemia and glycosuria, as well as a decrease in pancreatic insulin levels, compared with time-matched controls. In addition, the morphology of the pancreatic islets of nicotinamide-treated diabetic (db/db) mice showed an enhanced islet disorganization. By comparison, in NOD mice, nicotinamide prevented the decline in serum and pancreatic insulin levels and maintained normal islet architecture and insulin content. Our data shows that in contrast to its preventative effects on the development of autoimmune diabetes in NOD mice, chronic nicotinamide administration to obese diabetic (db/db) mice markedly accelerated the progression of diabetes. The results of our study caution against the use of nicotinamide in insulin-resistant states, such as type 2 diabetes.