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.

Study Overview

• Status: Completed
• Conditions: Prediabetic State
• Intervention / Treatment: Other: Oral glucose tolerance test

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Department of Community Health and Family Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic, PEAR participants

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PEAR Participants; All participants eligible for PEAR study. Each participant will be have fasting and oral glucose tolerance test data collected.	Other: Oral glucose tolerance test; 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.; Other Names: OGTT; Glucose tolerance test; Glucola; Glucose tolerance diagnostic test; Sugar beverage

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Florida

Publications and helpful links

Helpful Links

• Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) ClinicalTrials website

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: April 1, 2010
• First Submitted That Met QC Criteria: April 6, 2010
• First Posted (Estimate): April 7, 2010

Study Record Updates

• Last Update Posted (Actual): April 3, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Hypertension; Insulin Resistance; Blood pressure; Glucose; Diuretic; Glucose Tolerance Test; Hydrochlorothiazide; Atenolol; Beta-blocker; Metabolic adverse effects
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: UFIRB2372009 - N; U01GM074492 (U.S. NIH Grant/Contract)