Exercise and Inflammation in the Elderly

Not Applicable

Completed

Conditions: Inflammation
Insulin Sensitivity

Interventions: Other: Aerobic Exercise Training
Other: Weight Loss

Registration Number: NCT00753363

Lead Sponsor: VA Office of Research and Development

Brief Summary: Persistent low-grade inflammation and impaired fibrinolysis, are independent predictors of several chronic diseases highly prevalent in the older Veteran population including cardiovascular disease (CVD), stroke, and diabetes. Inflammation is likely to be a causative underlying mechanism of insulin resistance. Lifestyle changes such as weight loss and physical activity are advocated for the treatment of these chronic diseases and endpoints, and data are emerging which suggest that these treatments may be beneficial, in part, due to their anti-inflammatory effects. Identification of effective therapies that reduce chronic inflammation for Veterans is important given the widespread adverse health effects of a chronically elevated inflammatory state.

Detailed Description: This study will compare the effects of 6 month trial of aerobic exercise (AEX) vs. weight loss (WL) in older individuals on:

1. adipokine secretion and expression (tumor necrosis factor alpha, adiponectin);

2. adipose tissue and skeletal muscle inflammatory proximal receptor expression (adiponectin and tumor necrosis factor alpha expression) and signaling pathways; and

3. whether the changes in signal transduction are associated with changes in peripheral whole body insulin sensitivity by a hyperinsulinemic-euglycemic clamp.

The prevention and treatment of insulin resistance, the metabolic syndrome, and their CVD complications through exercise and weight loss could improve Veterans' health and reduce health care costs. Knowledge of their effectiveness has important implications for the cardiovascular health of Veterans given the widespread adverse health effects of chronic inflammation on vascular biology, skeletal muscle function and insulin action.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 119

Inclusion Criteria

Male and Female
45-80 yrs of age
Non-smoking for one year
Body mass index greater than 20 kg/m2 and less than 50 kg/m2
Menopause over 1 year

Exclusion Criteria

Symptomatic heart disease, coronary artery disease, congestive heart failure, or uncontrolled hypertension (blood pressure over 180/100 mm Hg) unless medically stabilized
Currently being treated for active cancer
Type 1 diabetes; Insulin or oral agent treatment for diabetes, poorly controlled diabetes fasting blood glucose over 160 mg/dl
Allergic to lidocaine
Untreated dyslipidemia with National Cholesterol Adult Treatment Panel III 10 year cardiac risk score greater than 10%, or receiving triglyceride lowering meds
Other systemic disorders that are not medically treated and stable
Taking beta-blockers, oral steroids, warfarin or any other medications interfering with fat/muscle metabolism that may not be safely discontinued temporarily for specific procedures (ie for 72 hours prior)
Abnormal response to exercise test (ST segment depression greater than 2mm, chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP above 240/120mm Hg, or other contraindications to exercise) *requires follow up treatment w/ primary MD for continued participation in study
Abnormal liver function
Abnormal renal function
Chronic pulmonary disease
Anemia hematocrit below 35 mg/dl, platelets below 100,000/cm3
Mini-mental state exam below 24, dementia or unstable clinical depression by exam
Aerobically trained with maximal oxygen consumption greater than 2 standard deviations above age-adjusted mean
Exercise group only: History of cerebrovascular disease (by medical history) with symptoms limiting the ability to exercise

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	Aerobic Exercise Training	6 months of aerobic exercise training
Arm 2	Weight Loss	6 months of weight loss

Primary Outcome Measures

Name	Time	Method
Insulin Sensitivity	Baseline and 6 month	Insulin resistance is defined as a reduction in glucose utilization rate elicited by a given insulin concentration. Glucose utilization is measured during a three hour hyperinsulinemic-euglycemic clamp and is presented as a measure of insulin sensitivity. This is one of the most sophisticated methods to measure insulin sensitivity.

Secondary Outcome Measures