Insulin Sensitivity/Resistance, Obesity, Skeletal Muscle, Weight Loss
Conditions
Keywords
weight loss, muscle mass
Brief summary
The investigators here propose to perform a prospective randomized intervention trial in post-menopausal women to investigate the endocrine network, which contributes to the changes in skeletal muscle mass during weight loss.
Interventions
BEHAVIORALmultimodal lifestyle intervention
multimodal lifestyle intervention will be performed to reduce body weight
BEHAVIORALplacebo
no intervention, only follow up
Sponsors
German Research Foundation
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI \> 27 kg/m2 (adults) * postmenopausal state
Exclusion criteria
* weight loss of more than 5kg in the last 2 months x * unhealthy patients with: severe chronic diseases including cancer within the last 5 years, severe heart disease, severe impairment of hepatic or renal function, severe anaemia or disturbed coagulation * eating disorders or any other psychiatric condition that would interact with the trial intervention * malabsorption * acute or chronic infections * severe hypertension * myopathy * food allergies * any other uncontrolled endocrine disorder * changes of smoking habits, diets or medication that strongly affects energy homeostasis within the last 3 months prior to study inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of myocellular insulin sensitivity (hyperinsulinemic clamp) during negative energy balance and during stabilized modification of body composition after weight loss. | 4 months | Analysis of myocellular insulin sensitivity by hyperinsulinemic clamp in mg•kg-1•min-1/(mU•L-1) |
| Changes of skeletal muscle mass (air displacement plethysmography) during negative energy balance and during stabilized modification of body composition after weight loss. | 4 months | Analysis of muscle mass (in % of body weight) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects on myocellular and adipose tissue mRNA expression | 4 months | Analysis of myocellular and adipose mRNA expression (RNA sequencing) in counts |
| Weight regain | 24 months | Analysis of body weight regain (BMI; kg/m2) during follow up |
| Effects on energy expenditure | 4 months | Measurement of energy expenditure (kcal/d), postprandial thermogenesis (%) and respiratory coefficient |
| Measurement of human gut microbiome at baseline, during weight loos, after weight loss (negative energy balance) and during stabilized modification of body composition 4 weeks after weight loss | 4 months | 16S rRNA sequencing and/or shotgun metagenomic pyrosequencing of the gut microbiota for assessment of microbiota composition and gene abundances. |
| Fat mass | 24 months | Analysis of body fat (kg and %) |
| Effects on myocellular and adipose tissue metabolism and substrate utilization | 4 months | Measurement of myocellular and adipose metabolism using microdialysis (glycerol (µmol/l), lactate (mmol/l), pyruvate (µmol/l), glucose (mmol/l)) during oral glucose load (180 minutes) |
Other
| Measure | Time frame | Description |
|---|---|---|
| FFA during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of fatty acids at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Analysis of predictive impact of several hormonal and metabolic parameters on body weight regain, course of insulin sensitivity and metabolism | 24 months | The effect of measured parameters (see other endpoints) on long-term course of BMI, muscle mass, insulin sensitivity and energy expenditure will be analyzed using mathematical models |
| Metanephrines during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of metanephrines at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Leptin during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of leptin at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Cortisol during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of cortisol at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Follistatin during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of follistatin at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Adiponectin during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement adiponectin at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| Natriuretic peptide during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of natriuretic peptide at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
| IGF-1 during negative energy balance and during stabilized modification of body composition after weight loss. | 12 months | Measurement of IGF-1 at baseline, during negative energy balance, during stabilized modification of body composition after weight loss and during follow up. |
Countries
Germany
Outcome results
None listed