Healthy Overweight/Obese
Conditions
Keywords
Type 2 diabetes mellitus, Shivering thermogenesis, skeletal muscle
Brief summary
The purpose of this study is to investigate the effect of prolonged shivering thermogenesis on glucose homeostasis in overweight/obese humans.
Interventions
Subjects will be exposed to shivering thermogenesis for at least 1 hour for 10 days
Sponsors
Study design
Intervention model description
a single arm, longitudinal study (10-day intermittent shivering exposure) in a pre-post design
Eligibility
Inclusion criteria
* Signed informed consent * Caucasian * Healthy (as determined by dependent physician based on medical questionnaire) * Man, or postmenopausal (defined as at least 1year post cessation of menses) woman * Aged 40 - 75 years at the start of the study * BMI 27 and 35 kg/m2 * Stable dietary habits (no weight loss or gain \>3kg in the past 3 months)
Exclusion criteria
* \- Not meeting all inclusion criteria * Medication use known to hamper subject's safety during study procedures * Co-morbidities to which the intervention or program that may pose as a complicating factor * Subjects diagnosed with cardiovascular diseases or cancer * Fasting plasma glucose ≥ 7.0 mmol/l * Haemoglobin \< 7.8 mmol/l for women, or \< 8.4 mmol/l for men * Previously diagnosed with type 2 diabetes * Abuse alcohol/drug abuse * Subjects who do not want to be informed about unexpected medical findings during the screening/study or do not wish that their physician is informed. * Engagement in structured exercise \> 2h per week * Participation in another biomedical study within 1 month before the first study * Smoking * Cold-acclimated, such as takes daily extended cold baths, works in a refrigerated environment, or regular cold-water swimming within 1 month of starting the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| area under the curve (AUC) of the glucose tolerance test | 1 day following cold exposure and following 9 consecutive days of cold exposure | area under the curve (AUC) of the glucose tolerance test before cold exposure, 1 day after cold exposure and after 9 consecutive days of cold exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| skeletal muscle GLUT4 translocation | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between skeletal muscle GLUT4 translocation, as assessed by wide-field microscopy both before and after cold acclimation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Heart rate | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between heart rate during cold exposure both before and after cold acclimation |
| Blood pressure | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between blood pressure during cold exposure both before and after cold acclimation |
| Energy expenditure | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between energy expenditure as assessed by indirect calorimetry both before and after cold acclimation |
| Substrate oxidation | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between substrate oxidation as assessed by indirect calorimetry both before and after cold acclimation |
| Plasma substrates | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between plasma substrates change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation |
| Gene expression in skeletal muscle | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between gene expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by RT-qPCR |
| Skeletal muscle intramyocellular substrate content | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between skeletal muscle intramyocellular substrate content both before and after cold acclimation |
| Protein expression in skeletal muscle | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between protein expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by western blot |
| Body temperatures | 1 day following cold exposure and following 9 consecutive days of cold exposure | Change in both skin and core temperature upon cold acclimation as assessed by means of temperatures sensors and a core temperature pill |
| Shivering activity | 1 day following cold exposure and following 9 consecutive days of cold exposure | Muscle shivering activity as determined by EMG. Comparison between shivering activity before and after cold acclimation |
| Plasma hormones | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between plasma hormones change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation |
| Insulin sensitivity | 1 day following cold exposure and following 9 consecutive days of cold exposure | Comparison between insulin sensitivity as estimated from the insulin and glucose concentrations during the OGTT both before and after cold acclimation. |
Countries
Netherlands