The Interaction of a Diabetes Gene Risk Score With Three Different Antihypertensive Medications for Incident Glucose Level Elevation.

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 three different antihypertensive medications.

Methods: We examined 376 non-diabetic 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 a 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 were 1.06 ([95% CI] 0.99, 1.14) (p=0.06) and 1.09 (0.99, 1.20) p=0.08), respectively. When results were examined by randomized medications, participants randomized to amlodipine had statistically significant odds for either outcome (OR 1.23 [1.03, 1.48] (p=0.01); 1.31 [1.06, 1.62] (p=0.01), respectively). No such risk increase was found in participants randomized to the other two medications.

Conclusions: A diabetes GRS predicts FG elevation in people treated with a CCB, but not with a ACEi or diuretic. These findings require confirmation.