Antihypertensive Medication Exposure as Risk for Impaired Glucose Tolerance: A PEAR Sub-Study

Antihypertensive Medication Exposure as Risk for Impaired Glucose Tolerance: A PEAR Sub-Study

The purpose of this study is to determine if, in a subset of patients treated with a beta-blocker and diuretic, prediabetes is detectable to a greater extent through a 2-hour oral glucose tolerance test (OGTT) compared to fasting glucose measurement.

Beta-blockers and diuretics have a well-established role in treating hypertension and are frequently used first-line. However, it is increasingly evident that these medications have harmful metabolic effects. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR - NCT00246519) study was a greater than 700 participant, randomized, parallel assignment trial, aimed at determining the genetic factors that influence response to both a beta-blocker (atenolol) and a diuretic (hydrochlorothiazide [HCTZ]). The PEAR trial design includes evaluation at baseline, after monotherapy with either medication, and after combination therapy with both medications. This pilot, PEAR sub-study aims to characterize the ability of two diagnostics tests (fasting glucose versus glucose 2-hours after an OGTT) to detect prediabetes development prior to blood pressure medication use, after monotherapy (with atenolol or HCTZ) and after combination therapy (with atenolol and HCTZ).

Inclusion Criteria:

• participation in PEAR:

  • an average seated home DBP > 85 mmHg and home SBP < 180 mmHg.
  • subjects must also have an average seated (> 5 minutes) clinic DBP between 90 mmHg and 110 mmHg and SBP < 180 mmHg.

Exclusion Criteria:

• secondary forms of HTN,
• patients currently treated with three or more antihypertensive drugs, isolated systolic HTN,
• other diseases requiring treatment with BP lowering medications,
• heart rate < 55 beats/min,
• known cardiovascular disease (including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease, including stroke and TIA),
• diabetes mellitus (Type 1 or 2),
• renal insufficiency (serum creatinine > 1.5 in men or 1.4 in women),
• primary renal disease,
• pregnancy or lactation,
• liver enzymes > 2.5 upper limits of normal,
• current treatment with NSAIDS,
• COX2-inhibitors,
• oral contraceptives or estrogen.