Opposing Effects of β Blockers and Angiotensin-Converting Enzyme Inhibitors on Development of New-Onset Diabetes Mellitus in Patients With Stable Coronary Artery Disease

Abstract

We utilized data from patients with stable coronary artery disease (CAD) to assess the risk of new onset diabetes (NOD) with beta-blockers, and to determine whether angiotensin converting enzyme (ACE) inhibition would modify this risk. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial randomized 8290 patients with stable CAD to trandolapril or placebo. The presence of NOD was assessed at each study visit over a median follow-up time of 4.8 years. We examined the risk of NOD associated with beta-blockers use with Cox regression models, adjusting for 25 baseline covariates, and tested whether this risk was modified by randomization to the ACE inhibitor. Of 6910 patients without diabetes mellitus at enrollment (1179 females/5731 males, mean age 64 ± 8 years), 4147 (60%) were taking beta blockers, and 733 (8.8%) developed NOD. We observed a significant interaction between beta-blocker use and randomization to ACE inhibitor with respect to new onset diabetes (p = 0.028). Participants taking beta-blockers assigned to the placebo group (N=2090) were at increased risk for NOD adjusting for baseline covariates (HR 1.63, 95% confidence interval 1.29, 2.05, p<0.001, while this risk was attenuated in those assigned to trandolapril (N=2057) (HR 1.11, 95% confidence interval 0.87, 1.42; p=0.39). Beta blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was reduced in patients treated concurrently with an ACE inhibitor. In conclusion, these data suggest that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking beta blockers.

Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

“…However, given the fact that there was marginal association between statin use and diabetes and the adherence to statin during outpatient follow-up was not properly evaluated, the association still remains uncertain in patients with coronary artery disease. In contrast to statin, we found an association of beta blocker use with new-onset diabetes consistent with previous studies in univariate analysis [ 8 , 33 ]; however, this association disappeared in multivariate analysis possibly due to more frequent use of beta blocker in AMI patients and the overwhelming diabetogenic effect of AMI compared with beta blocker use in multivariate analysis.…”

Risk of elevated resting heart rate on the development of type 2 diabetes in patients with clinically manifest vascular diseases

“…It seems that the predictive role of RHR in patients on beta-blocker treatment is greater (HR, 1.19; 95% CI, 1.04-1.37) than those without beta-blocker use (HR, 1.03 95% CI, 0.90-1.18), although this was not statistically significant. This is not surprising considering the fact that beta-blockers favor insulin resistance and increase the risk of developing diabetes (39).…”

Comparing six antihypertensive medication classes for preventing new‐onset diabetes mellitus among hypertensive patients: a network meta‐analysis

“…Also, it was reported that diabetes may be prevented by renin–angiotensin blockers . Recently, a number of trials on antihypertensive medications such as angiotensin‐converting enzyme inhibitors (ACEIs), ARBs, CCBs, diuretics and β‐blockers have explored whether these medications influenced NOD development .…”

“…CCB could significantly reduce the incidence of NOD, and CCB combined with ARB had metabolically neutral effects . Effects of β‐blockers on NOD patient are controversial which might contribute to a reduced mortality and morbidity of heart failure among patients with NOD , while it might trigger the development of NOD . It was also indicated that the use of diuretic is associated with a decreased incidence of NOD and prolonged diuretic treatment may result in an increased fasting glucose .…”