The Interaction of a Diabetes Gene Risk Score with 3 Different Antihypertensive Medications for Incident Glucose-level Elevation

Joshua I. Barzilay, Dejian Lai, Barry R. Davis, Sara Pressel, Hannah E. Previn, Donna K. Arnett

Research output: Contribution to journalArticlepeer-review


BACKGROUND Elevations of fasting glucose (FG) levels are frequently encountered in people treated with thiazide diuretics. The risk is lower in people treated with ACE inhibitors (ACEi). To determine if genetic factors play a role in FG elevation, we examined the interaction of a diabetes gene risk score (GRS) with the use of 3 different antihypertensive medications. METHODS We examined 376 nondiabetic hypertensive individuals with baseline FG <100 mg/dl who were genotyped for 24 genes associated with risk of elevated glucose levels. All participants had ≥1 follow-up FG level over 6 years of follow-up. Participants were randomized to treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACEi (lisinopril). Outcomes were an FG increase of ≥13 or ≥27 mg/dl, the upper 75% and 90% FG increase in the parent cohort from which the present cohort was obtained. Odds ratios were adjusted for factors that increase FG levels. RESULTS For every 1 allele increase in GRS, the adjusted odds ratios (ORs) were 1.06 (95% confidence interval (CI): 0.99, 1.14; P = 0.06) and 1.09 (95% CI: 0.99, 1.20; P = 0.08). When results were examined by randomized medications, participants randomized to amlodipine had statistically significant odds for either outcome (OR: 1.23; 95% CI: 1.03, 1.48; P = 0.01 and OR: 1.31; 95% CI: 1.06, 1.62; P = 0.01). No such risk increase was found in participants randomized to the other 2 medications. CONCLUSIONS A diabetes GRS predicts FG elevation in people treated with a CCB, but not with an ACEi or diuretic. These findings require confirmation. CLINICAL TRIALS REGISTRATION Trial number NCT00000542.

Original languageEnglish
Pages (from-to)343-349
Number of pages7
JournalAmerican Journal of Hypertension
Issue number4
StatePublished - Mar 16 2019

Bibliographical note

Funding Information:
This research was supported by contracts NO1-HC-35130 and HHSN268201100036C from the National Heart, Lung, and Blood Institute. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial investigators acknowledge contributions of study medications supplied by Pfzer, Inc. (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and fnancial support provided by Pfzer, Inc. No specifc funding was allocated for the work presented in this article.

Publisher Copyright:
© 2019 The Author(s).


  • area under curve
  • blood pressure
  • diabetes
  • fasting glucose
  • gene risk score
  • hypertension
  • net reclassification improvement

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'The Interaction of a Diabetes Gene Risk Score with 3 Different Antihypertensive Medications for Incident Glucose-level Elevation'. Together they form a unique fingerprint.

Cite this