Punthakee Z, Alméras N, Després J-P, Dagenais G R, Anand S S, Hunt D L, Sharma A M, Jung H, Yusuf S, Gerstein H C
Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
Diabet Med. 2014 Sep;31(9):1086-92. doi: 10.1111/dme.12512. Epub 2014 Jun 19.
Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance.
After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed.
Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 μg/ml with rosiglitazone and by 0.4 μg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids.
In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.
噻唑烷二酮类药物可减少异位脂肪，增加脂联素，并降低2型糖尿病患者体内的炎性脂肪因子、脂肪酸和血糖水平。我们旨在测定这些药物对空腹血糖受损和/或糖耐量受损人群的影响。
在接受约3.5年的8毫克罗格列酮（n = 88）或安慰剂（n = 102）治疗后，190名糖尿病缓解期预防评估（DREAM）试验参与者接受了腹部计算机断层扫描和双能X线吸收测定扫描。计算内脏和皮下脂肪组织面积、估计的肝脏脂肪含量、总脂肪和瘦体重，并评估空腹脂肪因子、游离脂肪酸、血糖和负荷后血糖水平的变化。
与安慰剂组相比，罗格列酮组参与者的瘦体重无差异，体脂多4.1千克（P < 0.0001），腹部皮下脂肪组织面积多31平方厘米（P = 0.007）。仅在对总脂肪进行校正后，罗格列酮组参与者的内脏脂肪组织面积比安慰剂组少23平方厘米（P = 0.01），肝脏与脾脏衰减比高0.08个单位（即肝脏脂肪更少；P = 0.02）。罗格列酮使脂联素增加15.0微克/毫升，安慰剂使其增加0.4微克/毫升（P < 0.0001）。罗格列酮对脂肪分布的影响并非独立于脂联素的变化。罗格列酮对空腹血糖（-0.36毫摩尔/升；P = 0.0004）和负荷后2小时血糖（-1.21毫摩尔/升；P = 0.0008）的影响不受脂肪分布调整、脂联素或游离脂肪酸变化的影响。
在空腹血糖受损/糖耐量受损人群中，罗格列酮与肝脏和内脏脂肪相对减少、皮下脂肪增加以及脂联素水平升高有关。这些作用似乎无法解释罗格列酮的降糖作用。
