Thursday, November 16, 2006

Do thiazide diuretics cause "benign" diabetes?

That thiazides precipitate "benign"diabetes is, in part, the argument made in the recent issue of the Archives of Internal Medicine in an editorial accompanying still another analysis of data from the ALLHAT trial.This study was a post-hoc analysis with a followup time of five years in which three groups were compared-those on a diuretic, those on a calcium channel blocker ( CCB) and those on an ace inhibitor (ACEi).

Those taking a CCB or a ACEi were statistically less likely to develop diabetes than those receiving a thiazide. Strong advocates of ALLHAT's preference for thiazides have put forth what I consider to be a strange argument that I think goes something like this; Yes, thiazides cause more diabetes but it doesn't seem to alter the outcomes. This they say because the various post hoc analyses fail to show a mortality excess. But the time frame of these studies is short-five years in the current Archives article with an average time of followup of 3 years- and are post hoc, sub group analyses which in the catechism of evidence based medicine are not very high on the evidentiary pecking order. The absence of proof of an effect is not the same as proof that the effect does not occur.

Although the editorialist repeatedly admonishes the readers with references to adhere to the principles of evidence based medicine I think it takes quite a leap of faith- not reliance on evidence, which so far is inadequate- to accept the notion that drug induced diabetes is harmless and somehow the patient with diabetes precipitated by thiazides is immune to the ravages of micro and macro vascular disease. While it is possible that the elevated blood sugar in the thiazide treated patients does not represent the disease that we designate as type 2 diabetes the burden of proof lies with the moving party i.e. the one saying this type of "diabetes" carries no cardiovascular or renal risk. The short period of follow up is a major weakness in the study particularly in regard to end stage renal disease but even CV effects may occur only after prolonged periods of elevated blood sugar as was the case in the Diabetes Control and Complications Trial.Further, nearly half of the study group did not have fasting glucose levels measured.

The patient with the metabolic syndrome which we think is driven by high insulin levels secondary to resistance to insulin in various tissues may also be the person with decreasing numbers of pancreatic beta cells and is already close to having elevated fasting blood glucose levels and have his glucose pushed up a bit by thiazides. It is hard to believe his risk of CV disease over the long run is not going to not be elevated. The deleterious processes of type 2 diabetes are at work for years before the fasting blood glucose becomes elevated.I have felt uneasy about prescribing to the diabetes-waiting-to- happen- patient a drug that is well recognized to increase the risk of diabetes.

In spite of the valid criticisms of ALLHAT's original design and its lack of correspondence to real life treatment of HBP we continue to see more re-analyses of the data that was flawed to begin with.

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