Triumphs And Tragedies In Advances In The Management Of Patients With Diabetes Mellitus:
13 Jan 2009
The need for long term studies to establish the best means of treating Diabetes, was underlined by Prof John Cleland from the University of Hull at the ESC Congress in Munich. Prof Cleland listed the latest treatment available for patients and voiced his concern about the side-effects and efficacy of available anti-diabetic drugs.
Treating Patients with Diabetes Mellitus
Treatment should be based, wherever possible, on the results of studies of substantial size and duration that measure outcomes that are meaningful to patients. We know that 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. A major barrier to obtaining evidence that long-term treatments are beneficial is the short and often insecure drug patent-life offered by regulatory agencies.
Short-termism forces regulators to accept surrogates instead of real clinical benefits. This deceives manufacturers, scientists, clinicians and patients into believing that blood glucose control is an important goal of treatment rather than a mere surrogate for real success. Buy generic diflucan Longer patent-life is a pre-requisite for obtaining good evidence that any treatment (for diabetes, blood pressure or lipids) designed to reduce long-term morbidity and mortality is safe and effective. Another alternative is to confine such studies only to patients with established cardiovascular disease and thus high event rates.
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 keto-acidosis or mortality and only small reductions in vascular events (21 patients difference after 17 years follow-up) with clear benefits only on subclinical micro-vascular 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. We know 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 micro-vascular 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 Generic propecia pills no prescription | generic cialis online buy | Buy zithromax without prescription