Mather Kieren J, Pan Qing, Knowler William C, Funahashi Tohru, Bray George A, Arakaki Richard, Falkner Bonita, Sharma Kumar, Goldstein Barry J
Division of Endocrinology and Metabolism, Indiana University, Indianapolis, Indiana, United States of America.
The Biostatistics Center, The George Washington University, Rockville, Maryland, United States of America.
PLoS One. 2015 Aug 27;10(8):e0136853. doi: 10.1371/journal.pone.0136853. eCollection 2015.
Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.
DESIGN, SETTING, PARTICIPANTS AND METHODS: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects.
Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman's rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman's rho = (+) 0.04, p = 0.03).
In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity.
分子数据表明脂联素可能直接调节尿白蛋白排泄。在糖尿病预防计划（DPP）中，我们在干预前后测量了脂联素和蛋白尿，并且我们之前报告过干预后脂联素增加。在此，我们使用DPP数据集来检验以下假设：与治疗相关的脂联素增加可能会降低肥胖患者的蛋白尿。
设计、地点、参与者与方法：我们评估了基线时血浆脂联素与尿白蛋白排泄之间的横断面相关性，以及脂联素与蛋白尿的治疗相关变化之间的关系。2553名受试者有基线和随访时的尿白蛋白肌酐比值（ACR（白蛋白肌酐比值））及血浆脂联素浓度数据。
校正年龄、性别和种族/民族后，我们在基线时观察到脂联素与ACR之间存在统计学显著但较弱的负相关（条件Spearman相关系数rho = (-) 0.04，p = 0.04）。尽管DPP治疗显著增加了血浆脂联素，但对ACR没有治疗效果，各治疗组之间的ACR也无差异。脂联素变化与蛋白尿变化之间存在较弱的正相关（非负相关）（校正后的Spearman相关系数rho = (+) 0.04，p = 0.03）。
在一个大型、特征明确的肥胖血糖异常受试者队列中，我们在基线时观察到循环脂联素浓度与尿白蛋白排泄之间存在较弱的负相关。与假设的效果相反，与治疗相关的血浆脂联素增加与ACR降低无关。在排除增加脂联素对降低肥胖患者ACR的有益作用之前，应在明显蛋白尿人群中评估脂联素变化与ACR变化之间的关联。
