Muscle Lipid and Insulin Resistance in the Elderly (MIRA)

University of Pittsburgh

Status

Completed

Conditions

Obesity

Treatments

Behavioral: Health Education Group

Behavioral: Exercise Group

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00765505

5R01AG021961 (U.S. NIH Grant/Contract)

0405764

Details and patient eligibility

About

This project will provide novel information concerning the ability of exercise to enhance the capacity for oxidative metabolism of fatty acids and improve insulin resistance in older adults who are at high risk for the development of type 2 diabetes. Ultimately this may help identify mechanisms and therapeutic targets implicated in skeletal muscle metabolic dysregulation. The proposed study is to conduct a randomized controlled exercise training intervention trial in older men and women. In addition, the response to exercise in these subjects will be compared to those of highly endurance-trained, age-matched athletes.

Full description

Hypothesis and Specific Aims:

To determine whether aerobic exercise improves both skeletal muscle fat distribution and insulin sensitivity of older men and women. We will test two hypotheses.

i. Physical exercise in older adults will decrease the amount of fat interspersed within muscle, specifically the fat between muscle groups (intermuscular adipose tissue) as well as decrease specific lipid metabolites within muscle cells, compared to controls.

ii. Exercise-induced improvements in insulin sensitivity of older men and women will be related to the changes in muscle fat content independent of changes in total body fat or visceral abdominal adipose tissue.
To determine whether increased capacity for oxidative fatty acid metabolism within muscle results in improved insulin sensitivity in older adults. We will test two hypotheses.

i. Exercise training will increase the capacity of muscle to oxidize fatty acids assessed both in vitro and in vivo.

ii. Improved capacity for oxidative fatty acid metabolism will predict improvements in insulin sensitivity.

Enrollment

92 patients

Sex

All

Ages

60 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

60 - 70 years of age
No weight gain/loss of >10 lbs in 6 months
Sedentary (No more than 1 continuous exercise/week) or Highly trained (>5 exercise sessions/week for a duration of one year or more)
Non-Smoker
BMI 18-38.0
Resting blood pressure less than 150mmHg systolic/95 mmHg diastolic
Normal glucose tolerance: Fasting glucose < 100 mg/dl or 2 hour glucose from OGTT < 140 mg/dl or impaired glucose tolerance (fasting glucose > 100 mg/dl < 126 mg/dl or 2 hour glucose from OGTT > 140 mg/dl but less than 200 mg/dl
Note from PCP/Cardiologist for exercise clearance if positive stress test symptoms were observed from GXT

Exclusion criteria

Clinically significant CVD including h/o MI
Peripheral Vascular Disease
Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
Clinically diminished pulse
Presence of bruits in lower extremities
Previous history of pulmonary emboli
Peripheral Neuropathy
Currently not engaged in a regular program and have a V)2 max pre-training value > 55 ml/kg-fat free mass-min., indicative of moderate fitness OR currently engaged in regular program and having a V)2 max value < 55 ml/kg-fat free mass-min.
Anemia (Hematocrit < 34%)
Any contraindications to moderate exercise
Inability and/or willingness to comply with the protocol as written
Active alcohol or substance abuse (Past 5 years)
Total cholesterol > 300 mg/dL
Triglyceride > 350 mg/dL
ALT > 80, AST > 80, Alk Phos > 240
Proteinuria (defined as > 1+ on routine dipstick) hypothyroidism (sTSH>8)
Therapeutic Doses of Nicotinic Acid
Type 2 Diabetes: Fasting Glucose > 126 mg/dl or 2 hour glucose > 200 mg/dl
Oral Glucocorticoids
Females currently on hormone replacement therapy (HRT) less than 6 months
Claustrophobia
Previous difficulty with lidocaine or other local anesthetic
Stress test symptoms:
- Positive ECG (>2mm ST segment depression) without PCP cardiologist permission to participate
- Signs or symptoms of cardiovascular decomposition (hypotensive response to exercise
- Onset of angina or angina like symptoms, shortness of breath, change in heart rhythm, signs of poor perfusion (light-headedness), tightness
- Hypotension