Effects of Weight Loss on Nutritional Mediated Hormone Secretion (RepDiet)

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

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.

Concentration of GLP-1 after different test meals will be analysed by ELISA before and after weight loss

Concentration of GIP after different test meals will be analysed by ELISA before and after weight loss

Concentration of Ghrelin after different test meals will be analysed by ELISA before and after weight loss

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))

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))

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))

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))

postprandial glucose concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis

postprandial pyruvate concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis

postprandial lactate concentration (physiological parameter) will be assessed in skeletal muscle and adipose tissue by microdialysis

-Weight loss mediated changes of meal induced GLP-1 concentration in insulin resistant vs insulin sensitive subjects

-Weight loss mediated changes of meal induced GIP concentration in insulin resistant vs insulin sensitive subjects

-Weight loss mediated changes of meal induced Ghrelin concentration in insulin resistant vs insulin sensitive subjects

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

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

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

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

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

Li L, Decker AM, Stobaus N, Beer F, Grittner U, Spranger J, Mai K. Weight loss did not modify macronutrient specific response of hormones and satiety in overweight and obese people without metabolic disease - results from a clinical trial. Clin Nutr. 2022 Apr;41(4):948-957. doi: 10.1016/j.clnu.2022.02.004. Epub 2022 Feb 19.

Fleischmann R, Decker AM, Kraft A, Mai K, Schmidt S. Mobile electronic versus paper case report forms in clinical trials: a randomized controlled trial. BMC Med Res Methodol. 2017 Dec 1;17(1):153. doi: 10.1186/s12874-017-0429-y.