Source: Diabetes Care  |  Posted 8 years ago

Patients who start antihypertensive treatment with a captopril-based regimen may be at significantly lower risk for developing diabetes compared to those who start with diuretics or beta-blockers, say researchers.

The Captopril Prevention Project (CAPPP) was a perspective intervention trial that compared the effects of therapy based on the angiotensin-converting enzyme inhibitor captopril with that of a conventional diuretic and/or beta-blocker antihypertensive regimen in 10 985 hypertensive patients. Captopril produced the same benefits as conventional therapy with respect to the reduction of cardiovascular morbidity and mortality, however, the incidence of new cases of diabetes was found to be 14% lower in the captopril-treated group.

To better understand this benefit, Anders Niklason, BSc, of the Sahlgrenska Academy at Goteborg University, Sweden, and colleagues further analysed the development of diabetes in different subcohorts of the non-diabetic CAPPP population and the contribution of various potential risk factors.

The CAPPP study included 10 413 non-diabetic participants, 5033 (mean age, 50.8; 2755 males) with newly diagnosed hypertension and 5380 (mean age, 52.9; 2765 males) previously treated individuals. Patients randomised to the captopril regimen received an initial dose of 50 mg daily, given in 1 or 2 doses. Hydrochlorothiazide and bendrofluazide were the most common diuretic treatments, and atenolol and metoprolol were the most commonly used beta-blockers in those patients taking conventional therapies.

A total of 67 239 patient years were accumulated during the course of the trial, and 717 patients developed diabetes. The researchers performed a multivariate analysis and identified several significant risk factors for developing diabetes, including glucose (hazard ratio [HR]=1.57; []P[] < .001), BMI (HR=1.11;[]P[] < .001), Hb (HR=1.020; []P[] < .001), age (HR=1.014; []P[] = .008), 'SBP X Untreated' (the interaction between systolic blood pressure at baseline and previously untreated patients, HR=1.012; []P[] < .001) cholesterol (HR=0.88; []P[] = .001), and prior antihypertensive treatment (HR=7.63; []P[] < .001).

The researchers developed a risk score based on the significant variables and divided the non-diabetic cohort into tertiles based on the score. Treatment with captopril was associated with a lower risk of diabetes within each tertile, and patients within the highest risk tertile had the greatest benefit from captopril treatment. In addition, the predictors for diabetes were found to differ between the previously treated and untreated subcohorts; only glucose, BMI and Hb were significant predictors in the treated group, whereas glucose, BMI, Hb, age, SBP at baseline, creatinine and cholesterol were significant in the previously untreated group.

The researchers note that glucose, BMI and Hb were the only common predictors among all models. "By using a risk score based on these factors, it may be possible to predict the patient group that would benefit most from captopril therapy in terms of lowering the risk for the development of diabetes," they conclude.