Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

September 2, 2009 updated by: National Institute on Aging (NIA)
The purpose of this study is to investigate the mechanisms by which physical inactivity and obesity alter skeletal muscle insulin signaling to cause insulin resistance and increase the development of impaired glucose tolerance (IGT).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aging is associated with a progressive development of impaired glucose tolerance (IGT), due to an increased peripheral tissue resistance to the action of insulin. Insulin resistance, a common state in both obese and sedentary individuals, eventually leads to the development of glucose intolerance, and type 2 diabetes with aging. Even in the absence of diabetes, insulin resistance is a key feature in various metabolic abnormalities that increase the risk for developing cardiovascular disease (CVD). Previous studies demonstrate improvements in glucose tolerance and glucose utilization following moderate energy restriction coupled with moderate intensity AEX. WL, through behavioral modification of diet and aerobic exercise (AEX), is perhaps the most effective way to treat as well as prevent insulin resistance and its associated metabolic complications of IGT and type 2 diabetes. Although these studies demonstrate the beneficial effect of weight loss (WL) and AEX on glucose tolerance and insulin action, not much is known about the cellular and molecular mechanisms by which these nonpharmacologic treatments improve glucose utilization in high-risk obese older individuals.

This study seeks to determine the cellular mechanisms by which aerobic exercise and weight loss alter skeletal muscle insulin signaling to improve insulin action in older glucose intolerant individuals. A second purpose is to determine whether certain genes (hereditary information) affect the way the body utilizes glucose in response to exercise and weight loss. In addition, adipose tissue is increasingly recognized as more than an inert depot serving not only to accept and store excess energy in the form of triglycerides, but also to secrete hormones and adipokines that have substantial effects on lipid and glucose metabolism. Furthermore, there are depot differences in metabolic function, as well as adipokine content. However, the physiology both underlying and consequential to these observations remains unknown. Thus, a third aim is to examine the effects of obesity on regional adipokine secretion and expression, and the relationship of adipokines to insulin resistance and the metabolic syndrome.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
      • Baltimore, Maryland, United States, 21201
        • Baltimore VA Medical Center

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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Men older than 50 yrs of age
  • Non-smoking (more than 5 years)
  • BMI greater than 25 kg/m2 and less than 50 kg/m2

Exclusion Criteria:

  • CAD, CHF, Myocardial infarction within 6 months or other symptomatic heart disease
  • History of stroke, peripheral arterial disease
  • Currently being treated for active cancer
  • On oral agents or insulin therapy for diabetes
  • Poorly controlled Dyslipidemia (abnormal concentration of lipids or lipoproteins in the blood)
  • Poorly controlled hypertension (BP > 180/95)
  • Other systematic disorders that are not medically treated and stable
  • Physical impairment limiting normal activity and other contraindications to exercise
  • Aerobically conditioned
  • Abnormal response to exercise (chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP > 240/120)
  • Taking warfarin/coumadin
  • Taking oral steroids
  • Abnormal renal function or liver function
  • Chronic pulmonary disease severe enough to require oxygen
  • Anemia
  • MMSE < 24, dementia

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: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: WL+AEX
Weight loss plus aerobic exercise
Behavioral: Dietary counseling
1 hour sessions, once per week, with a registered dietitian on the American Heart Association Step I diet with caloric intake for each volunteer adjusted by the dietitian to elicit a WL of ~0.2-0.4 kg/wk
Behavioral: AEX
Moderate aerobic exercise (75-80% HRR for 45 min) at the Baltimore GRECC exercise facility using treadmills 3 times per week for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Insulin stimulated glucose disposal
Time Frame: Baseline and 6 months
Baseline and 6 months
Content and activity of insulin signaling proteins from muscle biopsies
Time Frame: Baseline and 6 months
Baseline and 6 months
Glucose tolerance
Time Frame: Baseline and 6 months
Baseline and 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Aerobic capacity
Time Frame: Baseline and 6 months
Baseline and 6 months
Body weight/Composition
Time Frame: Baseline and 6 months
Baseline and 6 months
Cytokines
Time Frame: Baseline and 6 months
Baseline and 6 months
Other biomarkers (such as glucose, insulin etc)
Time Frame: Baseline and 6 months
Baseline and 6 months

Collaborators and Investigators

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

Sponsor

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Lyndon Joseph, PhD, National Institute on Aging (NIA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2004

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

September 2, 2009

First Submitted That Met QC Criteria

September 2, 2009

First Posted (Estimate)

September 3, 2009

Study Record Updates

Last Update Posted (Estimate)

September 3, 2009

Last Update Submitted That Met QC Criteria

September 2, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AG0120
  • K01AG021457 (U.S. NIH Grant/Contract)

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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