Training Effects on Fuel Metabolism

Study Overview
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Brief Summary
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The investigators are interested in how skeletal muscle processes fat and how this may affect insulin resistance. This is an important question since insulin resistance predates and predicts type 2 diabetes. The investigators are especially interested in learning about the effects of weight and training on insulin resistance. The investigators will study people before and after supervised aerobic or yoga training to identify differences in resting fat and sugar metabolism which may lead to differences in insulin resistance. The investigators will test these differences using stable isotopes, and the use of these stable isotopes is experimental. Overweight/Obese Group: Eight visits will be required at the University of Minnesota Clinical Research Unit. Four visits will be done before training (screen and 3 pre-training visits), 1 visit during the training, and 3 post-training visits will be done. In between, the training will take about 16 weeks and will be a supervised treadmill program. Lean/Trained Group: Four visits will be required at the University of Minnesota Clinical Research Unit (screen and 3 study visits).

Detailed Description
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Insulin resistance plays a critical role in the development of type 2 diabetes (T2DM), with skeletal muscle the largest site of insulin resistance in the human body. In sedentary humans, insulin resistance correlates with levels of intramyocellular lipid (IMCL) and lipid metabolites that adversely affect skeletal muscle glucose metabolism. However, even modest endurance training has been shown to reduce insulin resistance while increasing skeletal muscle IMCL. Moreover, lean endurance trained participants have IMCL levels comparable to those of patients with T2DM, yet have significantly lower insulin resistance. These findings suggest that the physiological changes caused by training protect against lipid induced insulin resistance and that this protection is present even at rest, however our preliminary data suggest that training facilitates utilization of readily available fuel, with lipid preferentially used over glucose when available. We will test the overarching hypothesis that training increases resting skeletal muscle lipid metabolism, as measured by markers of IMCL lipolysis, accumulation of fatty acid metabolites and mitochondrial utilization of fatty acids. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1-TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Official Title
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Training Effects on Fuel Metabolism

Conditions
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Healthy Subjects, Lean Trained Subjects, Overweight and Obesity

Intervention / Treatment
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* Behavioral: Running Program
* Behavioral: Yoga Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects Subjects 18 to 40 years of age. Subjects are capable of giving informed consent Overweight or obese Insulin resistant based on screening oral glucose tolerance testing. BMI 25 to 40 kg/m2 inclusive Stable weight for at least 3 months (± 5 lbs.) Sedentary status (self-report < 30 minutes/week regular exercise). Lean, physically active physically active subjects defined as 3-5 aerobic exercise sessions/week matched to age and gender generally healthy with normal fasting glucose levels (glucose ≤100 mg/dL). Exclusion Criteria: All subjects Subjects 18 to 40 years of age. Subjects are capable of giving informed consent Overweight or obese Insulin resistant based on screening oral glucose tolerance testing. BMI 25 to 40 kg/m2 inclusive Stable weight for at least 3 months (± 5 lbs.) Sedentary status (self-report < 30 minutes/week regular exercise). Lean, physically active physically active subjects defined as 3-5 aerobic exercise sessions/week matched to age and gender generally healthy with normal fasting glucose levels (glucose ≤100 mg/dL).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Lean Trained<br>Metabolic control | |
| Experimental: Obese or Overweight<br>Running Program Yoga Program | Behavioral: Running Program<br>* 16 week supervised running program<br>Behavioral: Yoga Program<br>* once weekly supervised yoga<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in insulin sensitivity between groups | Will use HOMA-IR and hyperinsulinemia-euglycemic clamp | Before and after exercise program (exercise program will take 16 weeks, expected average for evaluation will be 20 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in fitness level between groups | we will measure fitness level by treadmill based VO2 max testing. | before and after exercise program (exercise program will take 16 weeks, expected average for evaluation will be 20 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistance, lipid metabolism, diabetes