Type 2 Diabetes Mellitus (T2DM) is a widespread health condition characterized by impaired ability of the body to maintain glucose homeostasis. This impairment often leads to secondary complications, including heart disease, high blood pressure, and poor quality of life. While exercise and healthy eating are effective strategies in managing and preventing T2DM, data shows that long-term adherence to these methods are poor - especially among elderly, individuals with obesity and/or with physical limitations.
This clinical study explores cold exposure with shivering as a novel strategy to improve blood sugar control and heart health. In earlier research, spending time in mildly cold environments (around 15-17°C) for a few hours a day improved insulin sensitivity of T2DM patients. Interestingly, these benefits only occurred when the cold caused mild shivering. In a recent 10-day cold acclimation study with overt shivering for minimally 1 hour/day, we observed improved glucose tolerance in participants with overweight/obesity, as well as improved fasting lipid profiles. These results indicate that when accompanied with sufficient level of muscle activation, repeated exposure to cold can beneficially affect both glucose and lipid levels - both of which are impaired in people with T2DM.
In this study, we hypothesise that a 10-day cold acclimation with shivering will improve the (peripheral) insulin sensitivity of patients with T2DM, accompanied by enhanced skeletal muscle FA uptake and oxidation as assessed via the 11C palmitate uptake.
Patients are able to provide signed and dated written informed consent prior to any study specific procedures
Women are post-menopausal (defined as at least 1 year post cessation of menses)
Aged ≥ 40 years and ≤ 75 years
Patients should have suitable veins for cannulation or repeated venipuncture
Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
Participate in sports of physical activity at a moderate- to high-intensity more than 3 times a week, or as judged by the investigator
Being cold-acclimated, e.g. having taken daily extended cold baths, working in a refrigerated environment, or practicing regular cold-water swimming/ showering within 1 month of starting the study
Unstable body weight (weight gain or loss > 5 kg in the last three months)
Single group
Cold exposure with shivering
BehavioralCold exposure which elicits a minimally 80% increase in the baseline metabolic rate of participants.
Whole-body insulin sensitivity measured as glucose infusion rate (GIR) in µmol/kg/min during the stable period of the low- and high-insulin phase of the clamp.
1\) Hepatic insulin sensitivity measured as percent EGP suppression in µmol/kg/min; 2) Peripheral insulin sensitivity measured as Rd in µmol/kg/min. Determined by means of a hyperinsulinaemic-euglycaemic clamp.
11-C palmitate uptake and oxidation in liver and skeletal muscle, expressed in µmol/g/min
Determined by means of PET-CT scanning with a cervico-thoracic dynamic acquisition with 1-\[11C\]-palmitate (175 MBq).
24-hour systolic and diastolic blood pressure and heart rate
24-hour ambulatory blood pressure before and after the 10-day cold acclimation
Plasma metabolites
1. In the fasted state plasma metabolites such as glucose, insulin, free fatty acids, triglycerides, inflammatory markers, liver enzymes, etc. will be measured 2. Under cold- and insulin-stimulated conditions circulating metabolites and hormones during the first and last cold exposure, as well as during the hyperinsulinaemic euglycaemic clamp will be measured
Average 24-hour interstitial glucose concentrations
24-hour interstitial glucose values measured under normal living conditions via continuous glucose monitors
Energy expenditure
Energy expenditure will be assessed via indirect calorimetry before and after the 10-day acclimation during: * Baseline (room temperature) * Cold exposure * Baseline phase of the hyperinsulinaemic euglycaemic clamp * Low- and high-insulin phase of the hyperinsulinaemic euglycaemic clamp
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Université de Sherbrooke
Lead sponsor
Maastricht University Medical Center
Collaborator
