Thiazide-induced dysglycemia: it’s time to take notice

摘要

Almost a half century ago, Wolff et al. wrote [1]:nn“During the course of studies of hypertensive patients, including a double blind study, observations were made concerning the diabetogenic activity of benzothiadiazine derivatives. This activity was observed to occur in nonobese patients without a family history of diabetes as well as in obese hypertensives with such a family history. These observations suggest that benzothiadiazines should not be given to young or middle-aged hypertensives in whom there is a lengthy life expectancy and for whom alternative hypotensive therapy is feasible.” nnDespite these insightful recommendations, benzothiadiazine derivatives (most often hydrochlorothiazide [HCTZ]) are the first-line recommended therapy for hypertension, regardless of glycemic status [2]. Epidemiologic data, as well as data from randomized controlled trials, have associated a new diagnosis of diabetes with hypertension treatment that contains a thiazide diuretic, including chlorthalidone [3,4], HCTZ [5,6] and bendroflumethiazide [7]. There is controversy over the long-term significance of diuretic-induced diabetes [8], primarily related to the benefit of blood pressure lowering versus the hazard of dysglycemia. Recent data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that there is no increased risk for cardiovascular outcomes in those with chlorthalidone-induced hyperglycemia or diabetes [9]. However, this may, in fact, be due to a lack of power to detect a difference in outcomes in this subset of patients, since ALLHAT was not designed a priori for this comparison [10] and less than a quarter of the patients had a fasting glucose measurement during follow-up, with just over 3 years follow-up. In hypertensive patients followed for 15 years, diabetes associated with diuretics is linked to significant cardiovascular risk, as for diabetes from other causes [5].