Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes

University of Maryland Baltimore (UMB)

Status and phase

Terminated

Phase 4

Conditions

Diabetes Mellitus, Type 2

Treatments

Drug: Atenolol

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00925119

HP-00040291

K23HL091120 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Beta-blockers are medications used to treat cardiovascular disease (CVD) symptoms, including high blood pressure and chest pain. People with diabetes who receive beta-blockers may experience adverse health effects, but the exact cause of why this happens remains unknown. This study will examine the genetic factors that may influence how atenolol, a beta-blocker medication, affects fat breakdown, blood sugar levels, and heart function in people with type 2 diabetes.

Full description

People with diabetes who develop CVD have worse health outcomes than people without diabetes who develop CVD. Beta-blockers are medications used to treat high blood pressure, angina (i.e., chest pain), arrhythmias, and other CVD conditions. While beta-blockers are effective at treating these conditions, they may also have damaging effects on cholesterol or glucose levels, thereby possibly lessening their ability to prevent CVD events in people with diabetes. It is important to identify which patients may not benefit from receiving beta-blocker medications. Genetic factors may influence how people respond to beta-blocker medications. The purpose of this study is to evaluate the influence of genetic variation on beta-blocker-induced changes in insulin sensitivity, fat breakdown, and heart function in people with type 2 diabetes.

This study will enroll people with type 2 diabetes. At a series of up to three baseline study visits, participants will have a blood collection, a glucose tolerance test, an echocardiogram to obtain images of the heart, and biopsies of muscle from the thigh and fat from the stomach. All participants will then receive atenolol once a day for 8 weeks. During Week 1, participants will receive a low dose of atenolol. They will then attend a study visit at the end of Week 1, and study researchers will examine how well participants are tolerating the medication. If the atenolol is well tolerated, the dose will be increased. Study researchers will call participants 1 week after any dosage changes to monitor for side effects. Blood collection will occur again at a study visit at Week 4. At Week 8, participants will then attend up to three study visits for repeat baseline testing. Participants will then be slowly tapered off of atenolol over a 1-week period.

Enrollment

31 patients

Sex

All

Ages

21+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Type 2 diabetes
Pre-Diabetes

Exclusion criteria

Insulin therapy
Treatment with any beta-blocker in the 30 days before study entry
Asthma
Chronic obstructive pulmonary disease (COPD)
Greater than first degree heart block
Heart rate less than 60 bpm
Systolic blood pressure less than 90 mm Hg
Raynaud's phenomenon
Known history of angina, heart attack, heart failure, coronary revascularization, or automatic implantable cardioverter defibrillators
Pregnant
Creatinine clearance less than 35 ml/min
Hematologic dysfunction (white blood cell [WBC] count less than 3000 or hematocrit less than 28%)
Allergy to amide anesthetics