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

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.