Oncologic, Endocrine and Metabolic: Diabetic complications: progress in the development of treatments

In spite of treatment advances, the long-term complications of diabetes, retinopathy, nephropathy and neuropathy remain major causes of morbidity and mortality in diabetic patients. Prospective clinical studies with intensive-insulin therapy have correlated the development of diabetic complications to hyperglycaemia, and compelling evidence from animal studies has implicated the diabetes-induced increased flux of glucose through the sorbitol pathway as the metabolic link between hyperglycaemia and the development of complications. An expanded understanding of the pathogenic mechanisms that underlie diabetic neuropathy has supported the use of electrophysiological measurements as a reliable means of quantitating the progression of diabetic neuropathy and has also redefined realistic treatment goals for diabetic complications as the arrest or attenuation of the disease process rather than a reversal. Recent clinical studies with intensive insulin therapy and aldose reductase inhibitors clearly support these new treatment objectives. In long-term studies of five to eight years, intensive insulin therapy did not reverse the clinical signs and symptoms of diabetic neuropathy, but did prevent their appearance in patients without evidence of neuropathy at the study initiation. Consistent with these observations, intensive insulin treatment did not restore the pre-existing loss of nerve function but reduced the accelerated loss of nerve function, characteristic of diabetic neuropathy, to a rate normally observed with ageing. Similarly, in a one year study with the aldose reductase inhibitor tolrestat, nerve function was preserved even in patients with a long history of diabetic neuropathy.