The Polyol Paradigm and Complications of Diabetes

In the last decade, it has become increasingly evident that the clini cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol containing phospholipids and to changes in various tissue concentra tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli cations of diabetes.