Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy--preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline.

Impaired microcirculatory perfusion appears to be crucial to the pathogenesis of both neuropathy and retinopathy in diabetics. This in turn reflects a hyperglycemically mediated perturbation of vascular endothelial function that entails overactivation of protein kinase C, reduced availability of nitric oxide, increased production of superoxide and endothelin, impaired insulin function, diminished synthesis of prostacyclin/PGE1, and increased activation and endothelial adherence of leukocytes. These dysfunctions may be addressed with a supplementation program that includes high-dose antioxidants, fish oil, gamma-linolenic acid, chromium, arginine, carnitine, and ginkgolides. Pharmaceuticals likely to be of benefit in this regard include pentoxifylline, probucol, replacement estrogens, and inhibitors of angiotensin converting enzyme and aldose reductase.