Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the
polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic
diabetic neuropathy may appear as one of many forms and is frequently accompanied by
pain.
Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of
blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as
sorbinil, that inhibit the
enzyme aldose reductase. In various animal models of late complications of diabetes
sorbinil and other
aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of
sorbitol and depletion of myo-
inositol in nerve, lens and renal glomeruli.
Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II
cataracts and prevents
proteinuria in diabetic rats. Orally administered
sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another
aldose reductase inhibitor,
tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered
sorbinil appears in the urine as unchanged
drug. In the small number of clinical studies of diabetic patients with neuropathies
sorbinil has demonstrated limited
therapeutic effects. There is now a requirement for studies of its prophylactic use and its
therapeutic use in patients with
diabetic neuropathy in the early stages of development.