The treatment of patients with diabetes mellitus should be based, wherever possible, on the results of studies of substantial size and duration that measure outcomes that are meaningful to patients.
While treatment of hypertension and hyperlipidaemia reduce progression of micro-vascular disease, reduce vascular events associated with large vessel disease and improve the prognosis of patients with diabetes, in contrast, treatment of blood glucose has not convincingly reduced any of these problems, apart from sub-clinical micro-vascular disease.
Type 1 diabetes
Originally, diabetes mellitus was conceived as a syndrome of insulin deficiency, mainly affecting younger people and often associated with weight loss, glycosuria, ketoacidosis and often rapidly fatal. This syndrome requires Insulin replacement therapy, which is still predominantly given by intermittent subcutaneous injections. The evidence that tight insulin control is superior to a lax regimen is weak.
The largest study, DCCT ( n = 1,441 ), reported no reduction in diabetic ketoacidosis or mortality and only small reductions in vascular events ( 21 patients difference after 17 years follow-up ) with clear benefits only on subclinical microvascular disease. This study was not blinded and we know that unblinded studies tend to over-estimate benefit. More intense Insulin therapy was associated with substantial weight gain which may obviate any cardiovascular benefit of improved diabetes control. Insulin pumps, inhaled Insulin and pancreatic islet cell transplants are potential, but mainly theoretical alternatives. Potentially, very long-term studies are required to establish the best means of treating this disease.
Type II diabetes
Subsequently, a new population of patients with high insulin levels and hyperglycaemia ( insulin-resistance ) was identified. These were more commonly older patients, obese and had evidence of other cardiovascular diseases including hypertension and hyperlipidaemia. This population has increased markedly over the last 20 years, partly due to the growing proportion of the population who are elderly, partly because of the increase in obesity and partly because of the reduction in glucose thresholds required for diagnosis. Diabetes of this type does not really represent a distinct disease but rather just one end of the spectrum of the population. Blood glucose is continuously distributed in a similar way to blood pressure or heart rate. For each, there is an ideal natural range. Levels below this range or markedly above it cause acute illness and moderately elevated levels are associated with worse long-term outcome.
It is a giant assumption to suggest that using drugs to get patients back into the normal range is helpful or safe. It is known from experience with other diseases that this assumption is no longer tenable. Unfortunately, there is remarkably little evidence that treatment of moderate hyperglycaemia is of benefit to patients and concerns that treating hyperglycaemia associated with obesity, other perhaps than by treating obesity itself, is safe.
Although the microvascular complications of diabetes mellitus are of great concern, few older patients with diabetes survive long enough to develop them. For instance, over 10 years follow-up in the 411 patients of UKPDS-34 managed with low intensity regimen ( to maintain fasting blood glucose ( Xagena )