Non-Response to Exercise

Study Overview
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Brief Summary
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The purpose of this prospective intervention study is to find biomarkers and underlying pathomechanisms for non-response of improvement in glucose metabolism to exercise. An additional goal is to identify non-responders at an early stage, where prevention strategies (pharmacologically or by specific training) will be successful.

Detailed Description
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At baseline and end of study, an intensive metabolic phenotyping including cerebral insulin sensitivity as well as tissue biopsies are performed in overweight untrained healthy participants at high risk for type 2 diabetes. During the study, an individual exercise training at 80% VO2max is performed for 9 weeks. Before and after the training intervention, acute tissue biopsies after a standardized bout of exercise are obtained.

Official Title
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Non-Response to Exercise - Identification of Factors Contributing to Exercise Non-response.

Conditions
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Non-Responder

Intervention / Treatment
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* Behavioral: exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least one of the following risk factors for type 2 diabetes: overweight (BMI>27 kg/m2) impaired fasting glucose and/ or glucose tolerance former gestational diabetes family history for type 2 diabetes (first-degree relative) sedentary participant (< 2 exercise bouts/week) Exclusion Criteria: any kind of metal in or on the body thermosensory or heightened sensitivity to heating heightened sensitivity to loud noise or diseases of the ear claustrophobia Diabetes mellitus current pregnancy or breastfeeding cardiovascular diseases surgery, < 3 months ago participation in other clinical trials acute illness/infection, < 4 weeks ago severe mental illness hemoglobin, women < 11g/dl, men < 13g/dl potentially incompliant subjects and/or inability to absolve the exercise training glucose influencing drugs continuous analgetic drugs use of anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Behavioral: exercise training|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| exercise response with respect to changes in insulin sensitivity from baseline to post-intervention measurement | insulin sensitivity is measured before and after the training intervention by a 5-point-75g-OGTT and calculated by ISI Matsuda | 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| molecular mechanisms of non-response | molecular mechanisms of non-response in insulin sensitivity in peripheral insulin target tissues (skeletal muscle, adipose tissue) | 11 weeks | 
| differences in the adaptation process to exercise in responders versus non-responders | by assessing the acute inflammatory response in blood samples and tissue biopsies obtained directly after an acute bout of exercise, at the beginning, and the end of the exercise intervention | 11 weeks | 
| inflammatory response to exercise | local (muscle and fat) versus systemic (blood) inflammatory response to exercise | 11 weeks | 
| changes in brain insulin sensitivity by exercise, and brain differences in responders vs. non-responders | changes in brain insulin sensitivity, before and after the intervention | 11 weeks | 
| role of visceral fat mass in determining the non-response of insulin sensitivity to exercise | measured by MRI | 11 weeks | 
| identification of serum biomarkers of non-response |  | 11 weeks |