Ortega Moreno Lorena, Lamacchia Olga, Copetti Massimiliano, Salvemini Lucia, De Bonis Concetta, De Cosmo Salvatore, Cignarelli Mauro, Trischitta Vincenzo, Menzaghi Claudia
Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
PLoS One. 2015 Oct 14;10(10):e0140631. doi: 10.1371/journal.pone.0140631. eCollection 2015.
High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p<0.0001 for all). In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI), waist circumference, diabetes duration, glycated hemoglobin (HbA1c), albumin creatinine ratio (ACR) and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE)= -2.19 (0.59), p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE)=-4.42(1.16) ml/min/1.73m2 vs. -1.50 (0.67) ml/min/1.73m2, respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m2 increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21-1.64) in SGR sample, 53% (OR = 1.53; 95% CI 1.21-1.94) in FG sample, and 44% (OR = 1.44; 95%CI 1.27-1.64) in the two studies considered together (p<0.0001 for all). In the combined sample, further adjustment for the above mentioned covariates did not change the observed association (OR = 1.36; 95%CI 1.16-1.60; p<0.0001). Our study, so far the largest addressing the relationship between serum adiponectin and GFR in T2D, strongly suggests that the paradoxical inverse association, previously reported in different clinical sets, is also observed in diabetic patients. Further studies are needed to unravel the biology underlying this counterintuitive relationship.
在几种肾脏疾病情况下，血清脂联素水平会升高。在2型糖尿病（T2D）患者中，仅有稀少且相互矛盾的结果被报道，而T2D患者是肾功能不全的高危亚组人群。本研究的目的是通过对大量意大利糖尿病患者进行调查来填补这一知识空白。在两项意大利横断面研究的1243例T2D患者中，研究了血清脂联素水平与估计肾小球滤过率（采用慢性肾脏病流行病学协作组CKD-EPI方程计算的eGFR）之间的关联：878例来自圣乔瓦尼罗通多（SGR），365例来自福贾（FG）。在SGR样本中，血清脂联素与eGFR呈负相关[脂联素每增加1个标准差（SD）的β（标准误，SE）=-3.26（0.64）]，在FG样本中[β（SE）=-5.70（1.28）]，在两项研究合并样本中也是如此[β（SE）=-3.99（0.59）]；（所有p<0.0001）。在这项合并分析中，在调整了性别、吸烟习惯、体重指数（BMI）、腰围、糖尿病病程、糖化血红蛋白（HbA1c）、白蛋白肌酐比值（ACR）以及降糖、降压和降脂治疗后，该关联仍然显著[β（SE）=-2.19（0.59），p = 0.0001]。与正常白蛋白尿患者相比，在微量/大量白蛋白尿患者中，观察到脂联素每增加1个SD与低eGFR之间的关联更强[调整后的β（SE）分别为-4.42（1.16）ml/min/1.73m²和-1.50（0.67）ml/min/1.73m²；脂联素与白蛋白尿状态的p = 0.022]。对于脂联素每增加1个SD，在SGR样本中eGFR<60 ml/min/1.73m²的几率增加41%（比值比，OR = 1.41；95%置信区间，CI 1.21 - 1.64），在FG样本中增加53%（OR = 1.53；95%CI 1.21 - 1.94），在两项研究合并样本中增加44%（OR = 1.44；95%CI 1.27 - 1.64）（所有p<0.0001）。在合并样本中，对上述协变量进行进一步调整并未改变观察到的关联（OR = 1.36；95%CI 1.16 - 1.60；p<0.0001）。我们的研究是迄今为止针对T2D患者血清脂联素与GFR之间关系的最大规模研究，强烈表明先前在不同临床背景中报道的这种矛盾的负相关在糖尿病患者中也存在。需要进一步研究来阐明这种违反直觉关系背后的生物学机制。
