Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

This study has been completed.
Sponsor:
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00971594
First received: September 2, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

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 Intervention
Obesity
Glucose Intolerance
Exercise Capacity
Behavioral: Dietary counseling
Behavioral: AEX

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

Resource links provided by NLM:


Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • Insulin stimulated glucose disposal [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Content and activity of insulin signaling proteins from muscle biopsies [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Glucose tolerance [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Aerobic capacity [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Body weight/Composition [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Cytokines [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Other biomarkers (such as glucose, insulin etc) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: June 2004
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00971594

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

Publications:
Responsible Party: Alice S. Ryan, PhD, University of Maryland
ClinicalTrials.gov Identifier: NCT00971594     History of Changes
Other Study ID Numbers: AG0120, K01-AG-021457
Study First Received: September 2, 2009
Last Updated: September 2, 2009
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Insulin Resistance
Obesity
Glucose Intolerance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia

ClinicalTrials.gov processed this record on April 16, 2014