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This study aims to investigate whether maximum cold-induced non-shivering thermogenesis (e.g. thermogenesis as a consequence of BAT activity) differs between morning and evening.
Brown adipose tissue (BAT) recently emerged as a novel player in energy expenditure (EE) in humans as it combusts fatty acids and glucose towards heat. Human BAT can be activated by sympathetic stimulation resulting from cold exposure or treatment with sympathomimetic drugs. Short-term acclimation to mild cold was shown to reduce fat mass in obese subjects and decrease peripheral insulin resistance of patients with T2DM. Recently, in preclinical studies the investigators showed that BAT has a circadian rhythm. It is currently unknown whether this is also the case in humans. The investigators postulate that BAT activity should display a circadian rhythm that adapts to changes in circadian behavior, and may determine glucose/lipid levels throughout the day.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group | Experimental | Cold exposure in the morning and evening. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Personalized cooling protocol | Procedure | As an intervention, a personalized cooling protocol will be used in order to activate BAT and induce non-shivering thermogenesis. During the cooling procedure, subjects will be exposed to mild cold (approx. 14°C) for 150 min. Since the onset temperature of shivering shows a high interindividual variation, we will use a personal cooling protocol to ensure maximum non-shivering EE (and thus an equal maximum activation of BAT). The right temperature will be determined via a subjective method, e.g. to ask the subject if he or she experiences shivering. The time needed to achieve the right temperature is approximately 30-60 minutes. Then, the stable cooling period of 90 min is started. During this time the subject will be asked every 15 minutes whether he is experiencing shivering. If so, temperature will be increased with 2-3°C so that shivering just stops. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in cold-induced non-shivering thermogenesis between morning and evening | Thermogenesis is estimated by the change in energy expenditure after cold exposure, measured by indirect calorimetry. This will be measured in the morning and in the evening. | Change in cold-induced non-shivering thermogenesis between morning (total duration of measurement 120 minutes) and evening (total duration of measurement 120 minutes). The time frame comprising both the morning and evening measurement will be 72 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in glucose metabolism (mmol/L) | Serum glucose (mmol/L) before and during cold exposure in the morning versus the evening. | Change between morning and evening: measured at several timepoints during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Change in insulin (pmol/l) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mariette R Boon, MD, PhD | Leiden University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leiden University Medical Center | Leiden | 2333ZA | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36319877 | Derived | Sardjoe Mishre ASD, Straat ME, Martinez-Tellez B, Mendez Gutierrez A, Kooijman S, Boon MR, Dzyubachyk O, Webb A, Rensen PCN, Kan HE. The Infrared Thermography Toolbox: An Open-access Semi-automated Segmentation Tool for Extracting Skin Temperatures in the Thoracic Region including Supraclavicular Brown Adipose Tissue. J Med Syst. 2022 Nov 2;46(12):89. doi: 10.1007/s10916-022-01871-7. | |
| 35176767 |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D018149 | Glucose Intolerance |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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The study design encompasses a single-arm randomized intervention study using cold exposure.
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|
Serum insulin (pmol/l) before and during cold exposure in the morning versus in the evening. |
| Change between morning and evening: measured at several timepoints during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Change in lipid metabolism (cholesterol) (mmol/L) | Cholesterol (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) in serum (mmol/L). Before and during cold exposure in the morning and in the evening. | Change between morning and evening: measured at severaltime points during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Change in lipid metabolism (triglycerides) (mmol/L) | Triglycerides, glycerol and free fatty acids in serum (mmol/L). Before and during cold exposure in the morning and in the evening. | Change between morning and evening: measured at severaltime points during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Change in markers for sympathetic output | Norepinephrine, epinephrine (μM/ml) | Change between morning and evening: measured before and after cold exposure. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Skin temperature | Wireless iButtons and infrared camera | Change between morning and evening: measured every 60 seconds during cold exposure on both study days. The time frame comprising both the morning and evening measurement will be 72 hours. |
| Derived |
| Straat ME, Martinez-Tellez B, Sardjoe Mishre A, Verkleij MMA, Kemmeren M, Pelsma ICM, Alcantara JMA, Mendez-Gutierrez A, Kooijman S, Boon MR, Rensen PCN. Cold-Induced Thermogenesis Shows a Diurnal Variation That Unfolds Differently in Males and Females. J Clin Endocrinol Metab. 2022 May 17;107(6):1626-1635. doi: 10.1210/clinem/dgac094. |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006943 | Hyperglycemia |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |