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Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00971594
Recruitment Status : Completed
First Posted : September 3, 2009
Last Update Posted : September 3, 2009
Information provided by:
National Institute on Aging (NIA)

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Obesity Glucose Intolerance Exercise Capacity Behavioral: Dietary counseling Behavioral: AEX Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Age, Lifestyle, Muscle Mechanisms in Insulin Resistance
Study Start Date : June 2004
Actual Primary Completion Date : May 2008
Actual Study Completion Date : May 2008

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.

Primary Outcome Measures :
  1. Insulin stimulated glucose disposal [ Time Frame: Baseline and 6 months ]
  2. Content and activity of insulin signaling proteins from muscle biopsies [ Time Frame: Baseline and 6 months ]
  3. Glucose tolerance [ Time Frame: Baseline and 6 months ]

Secondary Outcome Measures :
  1. Aerobic capacity [ Time Frame: Baseline and 6 months ]
  2. Body weight/Composition [ Time Frame: Baseline and 6 months ]
  3. Cytokines [ Time Frame: Baseline and 6 months ]
  4. Other biomarkers (such as glucose, insulin etc) [ Time Frame: Baseline and 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00971594

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United States, Maryland
Baltimore VA Medical Center
Baltimore, Maryland, United States, 21201
University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
National Institute on Aging (NIA)
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Principal Investigator: Lyndon Joseph, PhD National Institute on Aging (NIA)

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Alice S. Ryan, PhD, University of Maryland Identifier: NCT00971594     History of Changes
Other Study ID Numbers: AG0120
K01AG021457 ( U.S. NIH Grant/Contract )
First Posted: September 3, 2009    Key Record Dates
Last Update Posted: September 3, 2009
Last Verified: September 2009

Keywords provided by National Institute on Aging (NIA):
weight loss
glucose metabolism

Additional relevant MeSH terms:
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Insulin Resistance
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases