Mather Kieren J, Funahashi Tohru, Matsuzawa Yuji, Edelstein Sharon, Bray George A, Kahn Steven E, Crandall Jill, Marcovina Santica, Goldstein Barry, Goldberg Ronald
Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Diabetes. 2008 Apr;57(4):980-6. doi: 10.2337/db07-1419. Epub 2008 Jan 11.
To determine whether baseline adiponectin levels or intervention-associated change in adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP).
Cox proportional hazards analysis was used to evaluate the contribution of adiponectin and treatment-related change in adiponectin to risk of progression to diabetes.
Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per approximately 3 microg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P < 0.001, P = 0.13 comparing groups). Baseline differences in adiponectin between sexes and race/ethnicity groups were not reflected in differences in diabetes risk. DPP interventions increased adiponectin levels ([means +/- SE] 0.83 +/- 0.05 microg/ml in the lifestyle group, 0.23 +/- 0.05 microg/ml in the metformin group, and 0.10 +/- 0.05 microg/ml in the placebo group; P < 0.001 for increases versus baseline, P < 0.01 comparing groups). These increases were associated with reductions in diabetes incidence independent of baseline adiponectin levels in the lifestyle and placebo groups but not in the metformin subjects (hazard ratio 0.72 in the lifestyle group (P < 0.001), 0.92 in the metformin group (P = 0.18), and 0.89 in the placebo group; P = 0.02 per approximately 1 microg/ml increase, P = 0.02 comparing groups). In the lifestyle group, adjusting for change in weight reduced, but did not remove, the effect of increased adiponectin.
Adiponectin is a powerful marker of diabetes risk in subjects at high risk for diabetes, even after adjustment for weight. An increase in adiponectin in the lifestyle and placebo groups was associated with a reduction in diabetes risk. However, these changes in adiponectin were comparatively small and less strongly related to diabetes outcome than baseline adiponectin levels.
确定在糖尿病预防计划（DPP）中，脂联素的基线水平或与干预相关的脂联素水平变化是否与糖尿病进展独立相关。
采用Cox比例风险分析来评估脂联素及脂联素与治疗相关的变化对糖尿病进展风险的影响。
在所有治疗组中，基线脂联素是新发糖尿病的一个强有力的独立预测指标（每升高约3微克/毫升的风险比；生活方式干预组为0.61，二甲双胍组为0.76，安慰剂组为0.79；所有P<0.001，组间比较P=0.13）。性别和种族/族裔组之间脂联素的基线差异并未反映在糖尿病风险差异中。DPP干预使脂联素水平升高（[均值±标准误]生活方式干预组为0.83±0.05微克/毫升，二甲双胍组为0.23±0.05微克/毫升，安慰剂组为0.10±0.05微克/毫升；与基线相比升高P<0.001，组间比较P<0.01）。这些升高与糖尿病发病率降低相关，在生活方式干预组和安慰剂组中独立于基线脂联素水平，但在二甲双胍治疗的受试者中并非如此（生活方式干预组风险比为0.72（P<0.001），二甲双胍组为0.92（P=0.18），安慰剂组为0.89；每升高约1微克/毫升P=0.02，组间比较P=0.02）。在生活方式干预组中，校正体重变化后降低了但并未消除脂联素升高的影响。
脂联素是糖尿病高危人群糖尿病风险的一个有力标志物，即使在校正体重后也是如此。生活方式干预组和安慰剂组中脂联素升高与糖尿病风险降低相关。然而，这些脂联素变化相对较小，与糖尿病结局的相关性不如基线脂联素水平强。
