Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication

Abstract

OBJECTIVE -The purpose of this study was to determine the baseline predictors of newonset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD. RESEARCH DESIGN AND METHODS -Among 19,257 hypertensive patients in theAnglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol Ϯ thiazide or amlodipine Ϯ perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores.RESULTS -NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine Ϯ perindopril in comparison with atenolol Ϯ thiazide treatment (hazard ratio 0.66 [95% CI 0.59 -0.74]), high HDL cholesterol, alcohol use, and age Ͼ55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise Ͼ5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.CONCLUSIONS -Baseline FPG Ͼ5 mmol/l, BMI, and use of an atenolol Ϯ diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects. Diabetes Care 31:982-988, 2008O bservational data suggest that hypertension is a risk factor for type 2 diabetes (1); hence, the two conditions frequently coexist. The increased propensity of the hypertensive population to develop diabetes is variably affected by different classes of antihypertensive medication. Recently, results of a network meta-analysis, using data from 22 clinical trials comprising 143,153 participants who did not have diabetes at randomization, suggested that the association between antihypertensive agents and incident diabetes is lowest for angiotensinogen receptor blockers and ACE inhibitors followed by calcium channel blockers and placebo, with ␤-blockers and diuretics increasing risk (2). The diabetogenicity of ␤-blockers and diuretics is consistent with their adverse impact on blood glucose levels, which has been reported for several decades (3-5). In contrast with the adverse effects of diuretics (3,6,7) and ␤-blockers (8) on the incidence of new-onset diabetes (NOD) in randomized trials, the bulk of trial evidence suggests that drugs that block the renin-angiotensin system exert a protective role against the development of NOD (2,9,10). These differential effects have influenced recommendations for antihypertensive drug sequencing contained in British g...

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