Chronic Cold Acclimation Stimulates the Browning of Subcutaneous White Adipose in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Adipose tissues, which include white adipose tissue (WAT) and brown adipose tissue (BAT), play an essential role in regulating whole-body energy homeostasis. Recent studies also reveal the presence of a subset of cells in WAT that could be induced by environmental or hormonal factors to become brown-like cells, and this beigeing process has been suggested to have strong antiobesity an antidiabetic benefits. More recently, one study showed that Short-term cold acclimation (10 days) improved insulin sensitivity, but did not activate the browning of subcutaneous white adipose in patients with type 2 diabetes mellitus. Here, investigators hypothesize that a chronic cold acclimation can activate the the browning of subcutaneous white adipose in patients with type 2 diabetes mellitus.

Detailed Description
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All subjects must receive metformin therapy, Patients have chronic cold acclimation intervention for 33 days. During the subsequent cold acclimation period, subjects are exposed to an environmental temperature of 14-15 °C for 33 consecutive days, with cold exposure for 2 h on the first day, 4 h on the second day and 6 h on the third through the 33th day.Biopsy for subcutaneous white adipose and skeletal muscle was performed before and after the intervention program under local anesthesia. The brown fat characteristics and insulin signaling of biopsy samples will be measured. The expression levels of uncoupling protein-1 (UCP-1), peroxisome proliferator-activated receptor r coactivator 1 a (PGC1a), growth factor receptor binding protein-10 (Grb10), PR domain containing 16 (PRDM16) will be determined before and after the intervention programme from the biopsy samples. In addition, a combination of positron emission tomography (PET) and computed tomography (CT) - with the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) as a tracer will be performed for brown adipose tissue before and after the intervention programme.Insulin sensitivity will be checked before and after the intervention programme by insulin clamp assay, and endothelial function will be measured by ultrasound.

Official Title
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Chronic Cold Acclimation Stimulates the Browning of Subcutaneous White Adipose in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes, Cold Acclimation

Intervention / Treatment
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* Other: Chronic cold acclimation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes 18-60 years old Body mass index 18.5-28 kg/m2 HbA1c < 6.5% Well controlled diabetes Exclusion Criteria: Type 1 diabetes Body mass index < 18.5 kg/m2 Body mass index > 28 kg/m2 Female Taking any drugs other than metformin haemoglobinA1c >=6.50%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic cold acclimation group<br>All patients will be conducted a chronic cold acclimation intervention for 33 days. | Other: Chronic cold acclimation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of UCP-1 expression in subcutaneous white adipose before and after cold acclimation program | The expression differences (fold) will be compared before and after cold acclimation program in UCP-1. | From baseline to 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brown adipose tissue, Subcutaneous white adipose tissue, White adipose tissue