Shivering and Glucose Homeostasis

The Effect of Prolonged Shivering Thermogenesis on Glucose Homeostasis in Overweight/Obese Humans

The purpose of this study is to investigate the effect of prolonged shivering thermogenesis on glucose homeostasis in overweight/obese humans.

Study Overview

• Status: Completed
• Conditions: Healthy Overweight/Obese
• Intervention / Treatment: Other: Cold exposure

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Cold acclimation arm; An oral glucose tolerance test will be performed on day 1 of the study. The next day (day 2), subjects will be exposed to shivering thermogenesis for at least 1 hour. The day after, an oral glucose tolerance test will be performed (day 3). The following 9 days, subjects will be exposed daily to shivering thermogenesis for at least 1 hour (day 4-12). On the last day (day 13), an oral glucose tolerance test will be performed.

Other: Cold exposure; Subjects will be exposed to shivering thermogenesis for at least 1 hour for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the curve (AUC) of the glucose tolerance test	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.	1 day following cold exposure and following 9 consecutive days of cold exposure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
skeletal muscle GLUT4 translocation	Comparison between skeletal muscle GLUT4 translocation, as assessed by wide-field microscopy both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Comparison between insulin sensitivity as estimated from the insulin and glucose concentrations during the OGTT both before and after cold acclimation.	1 day following cold exposure and following 9 consecutive days of cold exposure
Heart rate	Comparison between heart rate during cold exposure both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Blood pressure	Comparison between blood pressure during cold exposure both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Energy expenditure	Comparison between energy expenditure as assessed by indirect calorimetry both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Substrate oxidation	Comparison between substrate oxidation as assessed by indirect calorimetry both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Plasma substrates	Comparison between plasma substrates change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Plasma hormones	Comparison between plasma hormones change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Skeletal muscle intramyocellular substrate content	Comparison between skeletal muscle intramyocellular substrate content both before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure
Protein expression in skeletal muscle	Comparison between protein expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by western blot	1 day following cold exposure and following 9 consecutive days of cold exposure
Gene expression in skeletal muscle	Comparison between gene expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by RT-qPCR	1 day following cold exposure and following 9 consecutive days of cold exposure
Body temperatures	Change in both skin and core temperature upon cold acclimation as assessed by means of temperatures sensors and a core temperature pill	1 day following cold exposure and following 9 consecutive days of cold exposure
Shivering activity	Muscle shivering activity as determined by EMG. Comparison between shivering activity before and after cold acclimation	1 day following cold exposure and following 9 consecutive days of cold exposure

Collaborators and Investigators

• Sponsor: Maastricht University
• Investigators: Principal Investigator: Wouter van Marken Lichtenbelt, Prof., Maastricht University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ACTUAL): December 13, 2021
• Study Completion (ACTUAL): December 13, 2021

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (ACTUAL): August 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; skeletal muscle; Shivering thermogenesis
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: NL73487.068.20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No