Muscle Insulin Resistance in Aging (Mirage)

Study Overview
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Brief Summary
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The purpose of this study is to provide information regarding potential factors underlying metabolic dysfunction, insulin resistance, and loss of muscle mass in aging muscle.

Detailed Description
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Study Objectives: To determine the effects of diet-induced weight loss with and without the addition of exercise on mitochondrial biogenesis and energetic capacity, cellular redox state and insulin resistance. To determine the effects of diet-induced weight loss with and without the addition of exercise on intramyocellular lipid profiles. To determine the effects of diet-induced weight loss with and without exercise on skeletal muscle proteins mediating a program of autophagy and either loss or maintenance of muscle mass.

Official Title
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Muscle Insulin Resistance In Aging

Conditions
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Insulin Resistance, Sarcopenia

Intervention / Treatment
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* Behavioral: Exercise
* Behavioral: Energy Restriction-Induced Weight Loss


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 65-80 years of age Stable weight (No Gain/Loss of >10 lbs in 6 months) Sedentary (≤ 1 continuous exercise/week) Non-smoker BMI ≥ 30 kg/m2 Resting Blood Pressure ≤ 150 millimeters of mercury systolic and ≤ 95 millimeters of mercury diastolic Note from Primary care physician/Cardiologist for exercise clearance if positive stress test symptoms were observed from exercise test Must be willing to washout for 14 days from all diabetes medication and independent in self blood glucose monitoring during the washout periods (those with diabetes only) Exclusion Criteria: Clinically significant cardiovascular disease including history of myocardial infarction, within the past year 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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise training protocol<br> | Behavioral: Exercise<br>* Participants will complete a progressive 6-month exercise training program, 4-5 days per week, 45 min per session (180 min per week), consisting mostly of walking (both outside and on an indoor treadmill) but with the option to include stationary cycling, elliptical and rowing machines, similar to what we have utilized previously to elicit significant improvements in insulin sensitivity in both middle-age and older adults (52-55). Beginning at week 8, these subjects will also perform 2 non-consecutive resistance exercise sessions per week, 30 min per session, focused on major muscle groups using resistance machines (total days of exercise will still be 4 to 5).<br>|
| Experimental: Energy restriction-induced weight loss<br> | Behavioral: Energy Restriction-Induced Weight Loss<br>* The goal of the weight loss intervention will be to produce a weight loss of 10% body weight. A reduction of 500-1000 kcal/day - based on baseline weight -and low fat (<30% of calories from fat) diet will be used as part of the weight loss intervention.<br>|
| No Intervention: Health Education<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of intramyocellular lipids | A percutaneous muscle biopsy of the vastus lateralis will be obtained, and the intramyocellular lipids will be measured by high-performance liquid chromatography-tandem mass spectrometry. | Visit 3  22 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of insulin sensitivity | Insulin sensitivity will be measured using an intravenous catheter (glucose clamps) that will be placed in the antecubital vein for subsequent insulin and glucose infusions and for stable isotope infusions. This will measure insulin-stimulated changes in insulin signaling proteins and metabolism. | Visit 3  22 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistance, muscle, health education, exercise