[8] In this pathway both NADPH and NAD+ are consumed as cofactors for the enzymes AR and sorbitol dehydrogenase (SDH). AR flux-driven osmotic stress due to accumulation of sorbitol and oxidative stress due to changes in the ratio of NADPH/NADP+ and NAD+/NADH may mediate several diabetes complications. [9], [10], [11], [12], [13] Several studies show that AR inhibition reduces complications of diabetes in the lens, kidney, and peripheral nerves. [9], [10], [11], [12], [13]. This evidence concerns the gene AR and diabetes mellitus.