Weight Loss and/or Exercise Training to Discover Muscle Lipids Related to Insulin Sensitivity

Study Overview
=================
Brief Summary
-----------------
The investigators will use exercise training and weight loss to discover localized lipid species related to diabetes risk in people.

Official Title
-----------------
Weight Loss and/or Exercise Training to Discover Muscle Lipids Related to Insulin Sensitivity.

Conditions
-----------------
Diabetes, Pre-diabetes

Intervention / Treatment
-----------------
* Behavioral: Weight loss and exercise training intervention
* Behavioral: Weight loss Only Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese men and women with pre-diabetes; (BMI 30-40 kg/m2) Ages ranging from 30-60 years old; Individuals with: impaired fasting glucose (IFG), (between 100-125mg/dl, with post-prandial glucose (<140 mg/dl 2 hrs after 75g OGTT) impaired glucose tolerance (IGT), (normal fasting glucose <100mg/dl, with post-prandial glucose (>140 mg/dl 2 hrs after 75g OGTT) a combination of the two (IFG/IGT) (both impaired fasting glucose (100-125mg/dl), and impaired glucose tolerance (>140 mg/dl 2 hrs after 75g OGTT), will be verified using oral glucose tolerance testing at initial screening, and Sedentary (<2 hours/week of planned physical activity). To increase generalizability, and because each subject serves as their own control, women will be enrolled regardless of menopausal status, use of hormone replacement therapy and oral contraceptives. Exclusion Criteria: Regular exercise more than 2 hours/week, medications that could affect glucose, lipid metabolism, thyroid disease, history of lung disease, pregnancy, active cigarette smoking or exposure to second hand smoke, and Severe plasma lipid disorders.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Training and Weight Loss Intervention<br>Combination weight loss/exercise training, on insulin sensitivity, muscle lipid composition and localization in skeletal muscle. | Behavioral: Weight loss and exercise training intervention<br>* Combined weight loss and exercise training intervention<br>|
| Active Comparator: 4 Month Weight Loss Only Intervention<br>Use exercise training and weight loss as separate interventions in obese subjects with and without pre-diabetes. | Behavioral: Weight loss Only Intervention<br>* Weight loss Only Intervention<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity | Change in insulin sensitivity measured before and after the 3 month weight loss and exercise training intervention | baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in membrane localized diacylglycerol species | Change in concentration of membrane and cytosolic diacylglycerol species before and after the intervention. Diacylglycerol is a lipid known to be related to insulin resistance. | baseline and 3 months |