A perspective of aldose reductase inhibitors and diabetic complications

The clarity of findings in the recent trials of intensive insulin treatment has proven that improved glycemic control delays the onset and retards the progression of diabetic retinopathy, nephropathy, and neuropathy. The results have revealed, however, that - even with intensive insulin therapy - normalization of blood glucose values was not achieved: a significant burden of complications was thus left on the diabetic population. This amplifies the necessity of pharmacotherapy aimed at controlling the consequences of elevated glucose levels that persist due to inadequate glycemic control. Such pharmacotherapy is currently available through aldose reductase (AR) inhibitor treatment. The concept of AR inhibition rests on the evidence - obtained with preventive AR inhibitor treatment - that any surplus of glucose occurring in a diabetic tissue is metabolized by AR, thus triggering a cascade of pathophysiological changes that progress to the advanced lesions characterizing the triad of diabetic complications. Since, axiomatically, AR inhibitors cannot be more effective than normoglycemia, the benefit vs. risk evaluation and duration of AR inhibitor therapy should be considered relative to that of intensive insulin treatment. The use of AR inhibitors is deemed to be justified, therefore, in patients threatened by diabetic complications - particularly with early peripheral neuropathy - and who cannot achieve adequate glycemic control.