PREVENTION OF LONG-TERM COMPLICATIONS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Non-insulin-dependent diabetes mellitus (NIDDM) may be the most rapidl y-growing chronic disease in the world. Its long-term complications, i ncluding retinopathy, nephropathy, neuropathy, and accelerated macrova scular disease cause major morbidity and mortality. Although therapy t hat normalizes glycemia may prevent the development and delay the prog ression of long-term complications in NIDDM, as has been demonstrated in insulin-dependent diabetes mellitus (IDDM), no direct data exist to support the efficacy of ''intensive therapy'' in NIDDM. An alternativ e approach to preventing the development of long-term complications ma y be to intervene more distally, i.e., inhibit the mechanism(s) by whi ch elevated glucose levels cause complications. Potential pathogenic m echanisms include the accumulation of sorbitol and other biochemical c hanges in tissues with aldose reductase, and the modfication of protei ns by glycation. Pharmacologic probes, including aldose reductase inhi bitors and glycation inhibitors such as aminoguanidine, are currently under study and may provide an efficient means of preventing complicat ions, independent of the ambient glycemic level.