Nikotinamid og forebyggelse af insulinkrævende diabetes mellitus. Rationale, virkningsmekanisme, toksikologi og kliniske erfaringer. ENDIT Gruppe

IDDM is caused by an immune-mediated destruction of the insulin-producing beta cells. Beta cells are destroyed by induction of oxygen-derived free radicals (FR) and nitric oxide (NO), which results in perturbation of the mitochondrial respiratory system and DNA strand breaks. As a result of beta cell destruction, islet cell antibodies (ICA) can be demonstrated in the circulation. These antibodies can be detected up to eight years prior to overt IDDM. Nicotinamide, a vitamin B3 derivative, interferes with the immune mediated beta-cell destruction by reducing the content of FR and NO and thereby reducing their deleterious effects. At the same time, nicotinamide increases the intracellular NAD pool, thus increasing the energy supply of the cell. Nicotinamide protects against chemically induced as well as spontaneous diabetes in animal models of the disease. Recently, open clinical studies have suggested that nicotinamide when administered to humans can prevent or delay clinical onset of IDDM. To test the possible preventive effect of nicotinamide in IDDM, a prospective, randomized, placebo-controlled study is needed. A multicentre study including 18 European countries, Israel and Canada is planned to start during 1993.