Systemic Cross-talk Between Brain, Gut, and Peripheral Tissues in Glucose Homeostasis: Effects of Exercise Training

Study Overview
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Brief Summary
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Obesity and insulin resistance are worldwide epidemic and taking a major public health toll. Obesity also increases the risk for cognitive impairment which is also an increasing medical, societal, and economic challenge. The ultimate goal of this proposal is to develop a statistical model to assess systemic cross-talk between brain, peripheral tissues, gut microbiota and glucose metabolism. Integrated with exercise training intervention the results will be utilized to provide disease risk profiling and personalized predictions of exercise training as a drug free treatment for insulin resistance and type 2 diabetes.

Official Title
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Modelling Systemic Cross-talk Between Brain, Gut, and Peripheral Tissues in Glucose Homeostasis: Exercise Training and Public Health

Conditions
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Obesity, Insulin Resistance, Type2 Diabetes, Exercise Training

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: monozygotic twins body mass index (BMI) difference ≥ 2 kg/m2 and/or type 2 diabetes At least one co-twin is overweight (BMI > 25 kg/m2) Exclusion Criteria: BMI > 60 kg/m2 body weight > 170 kg waist circumference > 150 cm mental disorder or poor compliance eating disorder or excessive use of alcohol active ulcus disease diabetes requiring insulin treatment or fasting glucose > 10 mmol/l pregnancy past dose of radiation claustrophobia presence of ferromagnetic objects that would make MRI contraindicated

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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
Interventional Model Description: Exercise Training for six months
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise intervention<br>Six months of exercise training | Behavioral: Exercise training<br>* Subjects are required to exercise four times a week during six months. Exercise training consists of endurance training, resistance training and high-intensity interval training adjusted to subject's fitness level.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of exercise training - brain glucose uptake | Brain glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer. | The change from baseline to 6 months | 
| Effects of exercise training - brain inflammation | Brain inflammation (dimensionless; standistibution volume ratio) is measured with positron emission tomography (PET) with PK11195 tracer | The change from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of exercise training - liver glucose uptake | Liver glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer | The change from baseline to 6 months | 
| Effects of exercise training - adipose tissue glucose uptake | Adipose tissue glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer | The change from baseline to 6 months | 
| Effects of exercise training - whole-body insulin sensitivity | Whole-body insulin sensitivity (M-value; micromol/100g/min) during the hyperinsulinemic euglycemic clamp | The change from baseline to 6 months | 
| Effects of exercise training - ectopic fat | Ectopic fat content (%) is measured using magnetic resonance spectroscopy (MRS) | The change from baseline to 6 months |