Diabetic control and complications.

Premature mortality and morbidity in insulin dependent diabetes mellitus results from cardiovascular disease, retinopathy, renal failure, and neuropathy. In an attempt to establish definitively the role of chronic hyperglycaemia in the pathogenesis of these complications (and hence our ability to prevent them) the diabetes control and complications trial randomly allocated 1441 patients with insulin dependent diabetes to receive up to 10 years' conventional or intensified treatment. (Intensified insulin treatment aimed for long term near normoglycaemia with at least four home blood glucose assessments a day, three insulin injections a day, and monthly visits to a clinic with telephone contacts in between. Conventional treatment did not mean poor control.) The trial ended prematurely and last week reported substantially less risk of the development and progression of diabetic retinopathy, microalbuminuria (an indicator of high risk of progression to diabetic renal disease), and abnormal nerve function in patients treated intensively. ' The results confirm those of earlier smaller trials2-" and of a meta-analysis of some of these published earlier this year.6 A causal association between chronic hyperglycaemia and microvascular complications in insulin dependent diabetes mellitus now seems established. The size and high profile of the diabetes control and complications trial have resulted in wide dissemination of its message. The authors suggest that the findings may apply to almost anyone with diabetes, excluding only children and those with advanced diabetic complications. But the costs of the trial were enormous as over 560 health professionals participated. Applying its findings to people with diabetes has substantial implications for the provision of services. Do the study's findings provide good grounds for such care? The answer is probably yes. Although the most impressive result was the slowing of progression of retinopathy, the risk of sight threatening proliferative retinopathy was also reduced. A previous trial has also suggested that prolonged intensified insulin treatment reduces serious retinopathy and loss of sight.5 For nephropathy, the diabetes control and complications trial has again used surrogate end points (microalbuminuria and albuminuria), and the figures suggest retardation rather than absolute prevention of progression to albuminuria, which implies that factors other than hyperglycaemia play a part. Reichard and colleagues, however have previously reported that strict metabolic control provided complete protection over 7 5 years against a fall in glomerular filtration rate to subnormal values.5 Although substantially delaying renal failure and blindness is a valid goal for patients with diabetes and their carers, purchasers of health care services may be less enthusiastic about spending more money on diabetes if savings on renal replacement and photocoagulation are unlikely. What of the wider application of the trial's results? It contained mainly white patients with insulin dependent diabetes of short duration. The study of Reichard and colleagues strongly suggests that long duration of diabetes does not negate the benefits of improved glycaemic control, although none of the studies has examined patients with advanced complications.5 There are no data on the effect of intensified glucose control in patients with non-insulin dependent diabetes or belonging to ethnic minorities. The pathogenesis of microangiopathy is probably similar in all forms of diabetes so that the same rules for prevention will apply, but the potential risks of intensified treatment may be different in non-insulin dependent diabetes, especially given the possible causal link between hyperinsulinaemia and cardiovascular disease. The intensively treated patients in the diabetes control and complications trial showed a reassuring improvement in low density lipoprotein cholesterol concentration but were too young and at too low a risk for this to have any effect on the incidence of clinical disease. The UK Prospective Diabetes Study Group, which is based in Oxford, is currently examining the effects of different degrees of diabetic control in non-insulin dependent diabetes.7 Until it has reported we should be cautious about applying the results of the diabetes control and complications trial to patients with non-insulin dependent diabetes.