Cor Vasa 2007, 49(10):362-367 | DOI: 10.33678/cor.2007.129

Diuretics in the treatment of hypertension and the risk of new-onset diabetes

Jiří Widimský

Klinika kardiologie, Institut klinické a experimentální medicíny, Subkatedra kardiologie IPVZ, Praha, Česká republika

A recent meta-analysis of studies of treatment of hypertension has demonstrated that new-onset diabetes develops least often during therapy with angiotensin II receptor type 1 blockers (ARBs) and ACE inhibitors. However, these data do not make it clear whether the agents modulating the renin-angiotensin system exert a direct antidiabetogenic effect or whether they are only devoid of the diabetogenic action of beta-blockers and diuretics. The DREAM study, however, failed to show whether high doses of the ACE inhibitor ramipril, as compared with placebo, would effectively prevent the development of diabetes.
The relative reduction in cardiovascular events seen during antihypertensive therapy using thiaizide diuretics is identical in patients with normal fasting glucose, those with impaired fasting glucose as well as in patients with diabetes mellitus.
There has not been unanimity as to whether the diabetes developing during treatment with thiazide diuretics has a long-term adverse effect on cardiovascular and overall mortality. Some long-term studies do not seem to suggest such an effect. The impaired glucose tolerance occurring during diuretic-based therapy is due to the development of hypokalemia. A meta--analysis of 59 studies of diuretic-based antihypertensive therapy has documented a significant inverse correlation between decreased serum potassium levels and increased blood glucose levels. Each increment by 0.56 mmol/L in glucose levels was associated with a decrease in serum potassium levels by 1 mmol/L. The changes in potassium and glucose levels were 50% smaller in the subgroups of studies designed to prevent the development of hypokalemia.
Potassium depletion, whatever its cause, aggravates glucose tolerance whereas potassium repletion results in reversal of changes in glycemia within a short period of time. In hypertensive patients with the metabolic syndrome, a fixed combination of the ACE inhibitor trandolapril and calcium-channel blocker verapamil reduces the risk for new-onset diabetes as compared with the fixed combination of the ARB losartan and hydrochlorothiazide. However, the impaired glucose metabolism caused of the fixed ARB-hydrochlorothiazide combination is reversible and resolves upon therapy discontinuation and institution of the fixed combination of an ACE inhibitor and a calcium-channel blocker.
The long-term effect of combinations of various diuretics at different doses with ACE inhibitors or ARBs on glucose levels and glucose tolerance is unknown.Still, a clear recommendation for the time being is that, when treating patients with the metabolic syndrome, impaired fasting glucose, or with impaired glucose tolerance, preference should be given to ACE inhibitors or ARBs as the drug of first choice, calcium-channel blockers as second-line therapy, and a low-dose diuretic or indipamide as the drugs of third choice. A combination of a diuretic and a beta-blocker should not be used in these patients, as it is the most inappropriate one given the risk of new-onset diabetes.

Keywords: Diuretic; New-onset diabetes; Treatment of hypertension

Published: October 1, 2007  Show citation