Antihypertensives and Weight Gain

If antihypertensives associate with weight gain in patients, what might this ultimately imply about the driving force behind obesity?

The Caloric Balance Hypothesis tells us that medications can only make us fatter by either stimulating the appetite or making us sluggish.

The Lipophilia Hypothesis tells us that medications make us fatter by changing fat tissue metabolism, perhaps by driving us to over-secrete insulin or by changing our blood glucose concentration. (i.e. The establishment of a "positive caloric balance" results from obesity -- it does not cause it.)

So how might the phenomenon of weight gain on these drugs relate to the debate between these hypotheses?

1. A cursory review of the research pretty clearly tells us that antihypertensives closely associate not only with obesity but also with other diseases of civilization, like diabetes. Consider this article from the Journal of Hypertension, August 2004: "Old hypertensives and new diabetes."[1]

The authors write:

"The close relationship between diabetes and hypertension has been recognized for decades... New information indicates that resistance to insulin action and glucose uptake in peripheral tissues is a common underlying mechanism in hypertension and diabetes."

2. "Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism."[2]

The authors examined the effects of antihypertensives like thiazide, diuretics, and beta-blockers and concluded:

"[They] worsen insulin resistance and deteriorate lipoprotein metabolism... these data may explain the unexpectedly high incidence of the development of diabetes among treated hypertensives and the poor effect on risk for coronary artery disease intervention trials."

3. This article is from Diabetes Care from November 1991: "Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors."[3]

The authors write:

"The suspicion that pharmacological treatment may worsen the insulin resistance associated metabolic abnormalities and lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment."

These articles seem to bolster Lipophilia's contentions and contradict what we'd expect if Caloric Balance worked.

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1. Opie LH, Schall R. "Old hypertensives and new diabetes." J Hypertens. 2004 Aug;22(8):1453-8.

2. H O Lithell. "Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism." Diabetes Care March 1991 vol. 14 no. 3 203-209.

3. Berne C, Pollare T, Lithell H. "Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors." Department of Internal Medicine, Uppsala University, Sweden.

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