Regulation of B-Cell Function & Glucose Tolerance in Older People

August 10, 2011 updated by: US Department of Veterans Affairs
This VA CDA-2 proposal will test in detail if lifestyle intervention with aerobic exercise training improves the body's production of insulin in older people at risk to develop diabetes.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

There is a high prevalence of type 2 diabetes and impaired glucose tolerance (IGT) in the older population. Aging is associated with insulin resistance and impaired insulin secretion, with greater defects in older people with IGT. Beta-cell dysfunction is critical in the progression from normal glucose to tolerance to IGT and to diabetes.

In the Diabetes Prevention Program (DPP), lifestyle intervention with diet and exercise training significantly lowered the rate of progression from IGT to diabetes, and was particularly effective in older people. The mechanisms of lifestyle changes to prevent diabetes and the effects on beta-cell function remain unclear. Exercise is well-known to increase insulin sensitivity, although exercise effects on beta-cell function have not been specifically assessed. In a pilot study supported by local VA funds, one week of aerobic exercise training improved insulin sensitivity as expected, but also improved beta-cell function in sedentary older people with IGT, with no change in body weight/composition, fasting glucose or lipid/inflammatory parameters.

Based on my current VA RCDA project and the pilot study results, this VA CDA-2 proposal will test in detail the novel overall hypothesis that lifestyle intervention with aerobic exercise training leads to improved beta-cell function in human age-related glucose intolerance. The potential mechanisms of the age-associated decline in beta-cell function and whereby exercise training may improve beta-cell function will also be explored. Beta-cell function will be examined in relation to expected improvements in insulin sensitivity, and the effects of exercise will be isolated with weight maintenance and nutritional balance. The time course of exercise effects over three months, the acute and chronic effects of exercise training on beta-cell function, the effects of high vs. low intensity exercise training, and different important components of beta-cell function will be examined. The interaction between exercise training effects on beta-cell function in older people with IGT and potential mediators including free fatty acids (FFA)/FFA composition, intraabdominal fat, adipocytokines, and incretin hormones will be examined.

In light of the striking effectiveness of the DPP lifestyle intervention to prevent diabetes in older people with IGT, the decline in beta-cell function with even normal human aging, and the importance of beta-cell dysfunction in the progression to diabetes, it is of great interest to further define the potential, novel metabolic effects of exercise training on beta-cell function, particularly in the aging population. This project may provide initial steps to further determine the mechanisms whereby lifestyle changes prevent diabetes. This would provide critical information needed to translate research findings into clinical practice in order to prevent diabetes in the aging veteran population.

Study Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Sedentary (defined as activity level of no more than occasional short bouts of walking per week), community-dwelling older veterans and non-veterans age 60-80 years. Special recruitment efforts will focus on enrollment of veterans.
  • Fasting glucose <126 mg/dl and 2-hr glucose 140-199 mg/dl (IGT) during OGTT.
  • BMI 26-36 kg/m2.

Exclusion Criteria:

  • Current use of oral anti-diabetic agents, insulin, systemic steroids, beta-blockers, thiazides.
  • Abnormal screening exercise stress test: exercise-induced sustained arrhythmia, symptomatic myocardial ischemia, ischemic EKG changes (>2mm ST-T depression in non Q-wave lead) during screening maximum treadmill test.
  • Clinically significant cardiac disease defined as congestive heart failure (CHF) requiring pharmacologic therapy or New York Heart Association (NYHA) Class 3 or 4 cardiac status, atrial fibrillation, symptomatic obstructive valvular disease, high-grade AV block, unstable angina, or myocardial infarction within the last 12 months.
  • Participation in a physical therapy, exercise or diet program.
  • Significant orthopedic or musculoskeletal conditions.
  • Clinically significant renal disease and/or serum creatinine > 2.0 mg/dl.
  • Hemoglobin <10 g/l.
  • Clinically significant liver disease and/or ALT > 2.5 fold the upper limit of normal.
  • Clinically significant medical history or physical findings (e.g. chronic lung disease, cancer) detected at the screening assessment.
  • Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: 3
Control
Active Comparator: 2
Exercise
Behavioral: Exercise
Exercise
Active Comparator: 1
Exercise
Behavioral: Exercise
Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Exercise effect on beta-cell function at 3 months
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Exercise effects glucose tolerance, intraabdominal fat, lipids, glycerol, GLP-1, adiponectin, and leptin.
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Collaborators

American Diabetes Association

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

November 5, 2007

First Submitted That Met QC Criteria

November 5, 2007

First Posted (Estimate)

November 6, 2007

Study Record Updates

Last Update Posted (Estimate)

August 11, 2011

Last Update Submitted That Met QC Criteria

August 10, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDA-2-017-07F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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