Effects of Weight Loss on Nutritional Mediated Hormone Secretion

Study Overview
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Brief Summary
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Investigative trial with aim of the description of the hormonal and metabolic response to meals containing different compositions of macronutrients the metabolic response to these test meals in dependance of the hepatic and muscular insulin sensitivity and abdominal adipose tissue and effects of a weight loss on the hormonal response to these test meals containing different compositions of macronutrients Primary endpoint: Glucagon-like-peptide 1 (GLP-1), Glucose dependent insulinotropic peptide (GIP) and Ghrelin response to a nutritive stimulation characterized by different nutritional composition Secondary endpoints: differences of substrate utilization depending on the nutritive composition effects of different hepatic and muscular insulin sensitivity as well as impact of visceral fat mass on the hormonal and metabolic response effect of weight loss on the hormonal and metabolic response to different test meals Study procedure: After primary characterization 50 probands (male and female) will receive 3 different test meals within a randomised (meal order) controlled trial. The three different test meals differ in nutritional composition. During consumption of the test meal a characterization of the endogenous hormonal response and appetite behaviour is performed. A nutritional counselling is performed according to the guidelines of the German Nutrition Society (DGE) to ensure a stable nutritive behaviour in the three days before the test meal administration. After analysis of the hormonal response to these 3 different testmeals follows a weight reduction period over 3 months. Afterwards reevaluation of the probands (again administration of 3 different test meals over a period of 3 weeks) will be performed. Principal aim of the study: Gain of information leading to the understanding of the hormonal regulation of food intake. The individual variability shall be determined with the aim of an identification of patient groups which show various intensities of the responses to different macronutrients.

Official Title
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Analysis of the Variability of Appetite and Energy Regulating Hormones to an Acute Nutritive Stimulation by Different Combinations of Macronutrients

Conditions
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Weight Loss, Hormone Disturbance, Weight Gain

Intervention / Treatment
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* Dietary Supplement: nutritional stimulation via different testmeals
* Other: Nutritional counseling
* Dietary Supplement: formula diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI>27 kg/m2 given written informed consent Exclusion Criteria: type 2 diabetes patients treated by insulin or drugs influencing incretin levels lack of health insurance weight changes > 5 kg in the past 2 months pregnancy, breastfeeding patients with: severe heart failure impaired hepatic or renal function disturbed coagulation (biopsies will not be taken in those subjects) infection, malabsorption severe hypertension cancer within the last 5 years eating disorders or any other psychiatric condition that would interact with the trial intervention any other endocrine disorder changes of smoking habits or diets within the last 3 months prior to study inclusion *other severe chronic diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight loss<br>3 months weight loss intervention by behavioral intervention | Dietary Supplement: nutritional stimulation via different testmeals<br>* nutritional stimulation of hormonal response through different testmeals<br>Other: Nutritional counseling<br>* nutritional counseling for healthy eating behaviour<br>Dietary Supplement: formula diet<br>* formula diet to help weight loss<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incretine response to different nutritive stimulations | Concentration of GLP-1 after different test meals will be analysed by ELISA before and after weight loss | 3 month | 
| Incretine response to different nutritive stimulations | Concentration of GIP after different test meals will be analysed by ELISA before and after weight loss | 3 month | 
| Incretine response to different nutritive stimulations | Concentration of Ghrelin after different test meals will be analysed by ELISA before and after weight loss | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of the GLP-1 responses with the reduction of hunger (questionnaire) after a nutritive stimulation by different nutritional components | GLP-1 (concentration) will be measured by ELISA, hunger feeling will be measured by questionnaire using a visual analog score (from 1 (less) to 10 (more)) | 3 month | 
| correlation of the GIP responses with the reduction of hunger (questionnaire)after a nutritive stimulation by different nutritional components | GIP (concentration) will be measured by ELISA, hunger feeling will be measured by questionnaire using a visual analog score (from 1 (less) to 10 (more)) | 3 month | 
| Correlation of the Ghrelin responses with the reduction of hunger (questionnaire) after a nutritive stimulation by different nutritional components | Ghrelin (concentration) will be measured by ELISA, hunger feeling will be measured by questionnaire using a visual analog score (from 1 (less) to 10 (more)) | 3 month | 
| Correlation of the insulin responses with the reduction of hunger (questionnaire) after a nutritive stimulation by different nutritional components | insulin (concentration) will be measured by ELISA, hunger feeling will be measured by questionnaire using a visual analog score (from 1 (less) to 10 (more)) | 3 month | 
| -differences of substrate utilization depending on the nutritional composition | postprandial thermogenesis will be assessed by indirect caloriemetry | 3 month | 
| -differences of substrate utilization depending on the nutritional composition | postprandial glucose concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis | 3 month | 
| -differences of substrate utilization depending on the nutritional composition | postprandial pyruvate concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis | 3 month | 
| -differences of substrate utilization depending on the nutritional composition | postprandial lactate concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis | 3 month | 
| -differences of lipolysis depending on the nutritional composition | postprandial glycerol concentration (physiological parameter) will be assessed by microdialysis | 3 month | 
| -Change of hepatic insulin sensitivity after weight loss | hepatic insulin sensitivity assessed via endogenous glucose production measured in mg/kg/min | 3 month | 
| -Change of meal induced GLP-1 concentration during weight loss | Concentration of GLP-1 after different test meals will be analysed by ELISA | 3 month | 
| -Change of meal induced GIP concentration during weight loss | Concentration of GIP after different test meals will be analysed by ELISA | 3 month | 
| -Change of meal induced Ghrelin concentration during weight loss | Concentration of Ghrelin after different test meals will be analysed by ELISA | 3 month | 
| -Weight loss mediated changes of meal induced GLP-1 concentration in insulin resistant vs insulin sensitive subjects | Insulin sensitivity assessed via insulin sensitivity index | 3 month | 
| -Weight loss mediated changes of meal induced GIP concentration in insulin resistant vs insulin sensitive subjects | Insulin sensitivity assessed via insulin sensitivity index | 3 month | 
| -Weight loss mediated changes of meal induced Ghrelin concentration in insulin resistant vs insulin sensitive subjects | Insulin sensitivity assessed via insulin sensitivity index | 3 month | 
| Change of fat distribution after weight loss | total fat mass will be assessed | 3 month | 
| Change of fat distribution after weight loss | visceral fat mass will be assessed | 3 month | 
| Change of fat distribution after weight loss | hepatic fat mass will be assessed | 3 month | 
| Change of skeletal muscle mass after weight loss | skeletal muscle mass will be assessed | 3 month | 
| Prediction of weight regain (weight in kilograms and height in meters will be combined to report BMI in kg/m^2). | Analysis of the predictive impact of hormones like GLP-1, Ghrelin, GIP and insulin in the context of body weight regain. Linear and logistic regression models will be used to identify predictive biomarkers | 12 months | 
| Prediction of weight regain (weight in kilograms and height in meters will be combined to report BMI in kg/m^2). | Analysis of the predictive impact of hormones like GLP-1, Ghrelin, GIP and insulin in the context of insulin sensitivity. Linear and logistic regression models will be used to identify predictive biomarkers | 12 months | 
| Prediction of weight regain (weight in kilograms and height in meters will be combined to report BMI in kg/m^2). | Analysis of the predictive impact of hormones like GLP-1, Ghrelin, GIP and insulin in the context of insulin sensitivity. Linear and logistic regression models will be used to identify predictive biomarkers | 24 months | 
| Prediction of weight regain (weight in kilograms and height in meters will be combined to report BMI in kg/m^2). | Analysis of the predictive impact of hormones like GLP-1, Ghrelin, GIP and insulin in the context of body weight regain. Linear and logistic regression models will be used to identify predictive biomarkers | 24 months | 
| To analyse the long term course of body weight after 12 month | Measurement of body weight after 12 months | 12 months | 
| To analyse the long term course of body weight after 24 month | Measurement of body weight after 24 months | 24 months | 
| To analyse the long term course of body weight after 36 month | Measurement of body weight after 36 months | 36 months | 
| To analyse the long term course of body weight after 48 month | Measurement of body weight after 48 months | 48 months |