Study on Mechanisms of Changes in Liver Disease and Sex Steroid Metabolism During Weight Loss

Study Overview
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Brief Summary
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The main objective of the study is to gain insight in the early dynamics and mechanisms of recovery of liver disease and sex steroid metabolism during weight loss in obese men and women and to investigate whether surgical weight loss has differential effects as compared to weight loss with life style measures. In addition, we want to evaluate the postprandial hypoglycemic reactive syndrome (PPHRS) in these patients using a standard chewable meal. Secondary objectives are investigating determinants for the changes in sex steroids, liver disease and PPHRS. Possible determinants to be investigated are adipocytokine secretion patterns, body composition, resting metabolism rate, weight loss per se and changes in fat distribution, parameters of fatty acid metabolism, … .

Official Title
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Study on Mechanisms of Changes in Liver Disease and Sex Steroid Metabolism During Weight Loss

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Gastric bypass surgery
* Behavioral: Conservative weight loss program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained BMI > 35 kg/m² Exclusion Criteria: Primary or secondary hypogonadism due to genetic causes (Kallman syndrome etc.), tumors, infiltrative diseases, infections, pituitary apoplexy, trauma, critical illness, chronic systemic illness or intentional. Type 2 Diabetes Mellitus treated with insulin or GLP-1 analogues Current or recent use of insulin, corticosteroids, opiates (on a daily basis), growth hormones, androgen- or estrogen analogs, levothyroxine, anti-retroviral drugs or antipsychotics Cancer (within < 5 years) High-grade malignancies Serious co-morbidities such as renal, hepatic of cardiac failure Known or suspected abuse of alcohol or narcotics Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gastric Bypass Surgery<br>Solid mixed meal tolerance test, MRI, CT, anthropometrics, liver biopsies, fat biopsies, muscle biopsies | Procedure: Gastric bypass surgery<br> <br> |
| Conservative weight loss<br>Solid mixed meal tolerance test, MRI, CT, anthropometrics, liver biopsies, fat biopsies, muscle biopsies | Behavioral: Conservative weight loss program<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in sex steroids | The change in sex steroids will be compared between the conservative and the gastric bypass group. | Baseline, 3 weeks, 6 weeks, 6 months, 1 year. | 
| Change from baseline in liver fat | The change in liver steatose will be compared between the conservative and the gastric bypass group | Baseline, 6 months, 1 year | 
| Correlation in changes in liver fat en changes in sex steroids |  | baseline, 6 months, 1 year |