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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Prediabetic State

Intervention / Treatment
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* Other: Oral glucose tolerance test


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PEAR Participants<br>All participants eligible for PEAR study. Each participant will be have fasting and oral glucose tolerance test data collected. | Other: Oral glucose tolerance test<br>* For assessment of dysglycemia, 75 grams of glucose solution by mouth at 3 PEAR study visits for all enrolled participants: baseline, single drug therapy assessment, and dual drug therapy assessment.<br>* Other names: Sugar beverage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | A single cohort of patients was followed through participation in the parent study, PEAR, and had both fasting and 2-hour OGTT labs evaluated at three time points. At each of these time points the two methods for evaluating prediabetes were compared. Consistent with the definition for prediabetes recommended by the American Diabetes Association, a fasting glucose above 99mg/dL or 2-hour oral glucose tolerance test glucose above 139mg/dL was considered prediabetic for this study. | Baseline, 9 weeks, and 18 weeks after initiation of PEAR intervention(s) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose, Glucose Tolerance Test, Insulin Resistance, Metabolic adverse effects, Hypertension, Beta-blocker, Atenolol, Diuretic, Hydrochlorothiazide, Blood pressure