The Interaction of a Diabetes Gene Risk Score With 3 Different Antihypertensive Medications for Incident Glucose-level Elevation (original) (raw)

Elevations of fasting glucose (FG) levels are commonly encountered in people treated for hypertension (HTN). A high prevalence of insulin resistance 1,2 and of obesity 3 underlie these associations. The choice of medications used for the treatment of HTN also influences the risk for incident glucose elevations: thiazide diuretics increase risk, 4 whereas ACE inhibitors (ACEi) lower risk. 5 In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) the risk of incident diabetes mellitus (DM) (≥126 mg/dl) at 2-year follow-up among nondiabetic individuals at baseline was highest among users of the thiazide-like diuretic chlorthalidone (9.3%) and lowest among users of the ACEi lisinopril (5.6%). 6 Users of the calcium blocker amlodipine had an intermediate risk (7.2%). Over the past 15 years, many gene variants have been identified that increase the risk for elevated FG levels and for DM. 7 To our knowledge, no study has examined whether these genes interact with medications used to treat HTN to increase FG levels. In this study we determine (i) if a gene risk score (GRS), based on gene polymorphisms that predispose to glucose elevation, interacts with the 3 primary antihypertensive medications used in ALLHAT to increase the risk of FG level elevations in nondiabetic participants (drug-gene interaction) and (ii) whether a GRS improves the discriminatory ability of traditional risk factors for predicting new-onset glucose disorders in persons treated for HTN with different antihypertensive medications.