Non-Responder
Conditions
Brief summary
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
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.
Interventions
BEHAVIORALexercise training
Sponsors
University Hospital Tuebingen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| exercise response with respect to changes in insulin sensitivity from baseline to post-intervention measurement | 11 weeks | insulin sensitivity is measured before and after the training intervention by a 5-point-75g-OGTT and calculated by ISI Matsuda |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| differences in the adaptation process to exercise in responders versus non-responders | 11 weeks | 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 |
| inflammatory response to exercise | 11 weeks | local (muscle and fat) versus systemic (blood) inflammatory response to exercise |
| molecular mechanisms of non-response | 11 weeks | molecular mechanisms of non-response in insulin sensitivity in peripheral insulin target tissues (skeletal muscle, adipose tissue) |
| role of visceral fat mass in determining the non-response of insulin sensitivity to exercise | 11 weeks | measured by MRI |
| identification of serum biomarkers of non-response | 11 weeks | — |
| changes in brain insulin sensitivity by exercise, and brain differences in responders vs. non-responders | 11 weeks | changes in brain insulin sensitivity, before and after the intervention |
Countries
Germany
Outcome results
None listed