Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes.
Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes.
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DOI：
10.2337/dc12-0180
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发表时间：
2012-11
期刊：
影响因子：
16.2
通讯作者：
Deelman LE
中科院分区：
文献类型：
--
作者：
Hellemons ME;Mazagova M;Gansevoort RT;Henning RH;de Zeeuw D;Bakker SJ;Lambers-Heerspink HJ;Deelman LE
微量或大量白蛋白尿的发生与心肾并发症的风险增加有关，特别是在糖尿病患者中。为了预防转变为微量或大量白蛋白尿，需要在经典风险标志物之上的更准确的预测标志物。我们研究了一个有前途的新标志物，生长分化因子（GDF）-15，以预测2型糖尿病（T2 DM）向白蛋白尿增加阶段的转变。此外，我们研究了GDF-15在非糖尿病高血压（HT）受试者中的潜力。病例组和对照组受试者选自PREVEND队列，这是一项关于蛋白尿自然病程的大型（n = 8，592）前瞻性一般人群研究，随访时间>10年，并重复进行蛋白尿测量。我们发现24例T2 DM和50例HT病例受试者从正常白蛋白尿转变为大量白蛋白尿，9例T2 DM和25例HT病例受试者从微量白蛋白尿转变为大量白蛋白尿（平均随访2.8年）。稳定性蛋白尿的对照受试者在年龄、性别、蛋白尿状态和糖尿病病程方面配对。在白蛋白尿转变之前测量样品中的GDF-15。在转换之前，T2 DM病例受试者的GDF-15显著高于对照受试者（中位数[IQR] 1，288 pg/mL [885- 1，546] vs. 948 pg/mL [660- 1，016]，P < 0.001）。根据GDF-15的SD，白蛋白尿转变的比值比显著增加（2.9 [95% CI 1.1-7.5]，P = 0.03）。GDF-15还改善了白蛋白尿转变的预测，C统计量显著增加（从0.87增加到0.92，P = 0.03），综合辨别力改善（0.148，P = 0.001）。在HT中，GDF-15也与白蛋白尿阶段的转变独立相关（2.0 [1.1-3.5]，P = 0.02），并显著改善预测。我们确定GDF-15是一种临床上有价值的标记物，用于预测T2 DM患者白蛋白尿阶段的转变，超过了传统的风险标记物。这些发现在非糖尿病HT受试者中得到证实。
Development of micro- or macroalbuminuria is associated with increased risk of cardiorenal complications, particularly in diabetes. For prevention of transition to micro- or macroalbuminuria, more accurate prediction markers on top of classical risk markers are needed. We studied a promising new marker, growth-differentiation factor (GDF)-15, to predict transition to increasing stage of albuminuria in type 2 diabetes mellitus (T2DM). In addition, we looked at the GDF-15 potential in nondiabetic subjects with hypertension (HT). Case and control subjects were selected from the PREVEND cohort, a large (n = 8,592), prospective general population study on the natural course of albuminuria, with >10 years of follow-up and repeated albuminuria measurements. We found 24 T2DM and 50 HT case subjects transitioning from normo- to macroalbuminuria and 9 T2DM and 25 HT case subjects transitioning from micro- to macroalbuminuria (average follow-up 2.8 years). Control subjects with stable albuminuria were pair matched for age, sex, albuminuria status, and diabetes duration. GDF-15 was measured in samples prior to albuminuria transition. Prior to transition, GDF-15 was significantly higher in case subjects with T2DM than in control subjects (median [IQR] 1,288 pg/mL [885–1,546] vs. 948 pg/mL [660–1,016], P < 0.001). The odds ratio for transition in albuminuria increased significantly per SD of GDF-15 (2.9 [95% CI 1.1–7.5], P = 0.03). GDF-15 also improved prediction of albuminuria transition, with significant increases in C statistic (from 0.87 to 0.92, P = 0.03) and integrated discrimination improvement (0.148, P = 0.001). In HT, GDF-15 was also independently associated with transition in albuminuria stage (2.0 [1.1–3.5], P = 0.02) and improved prediction significantly. We identified GDF-15 as a clinically valuable marker for predicting transition in albuminuria stage in T2DM beyond conventional risk markers. These findings were confirmed in nondiabetic HT subjects.
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通讯作者：
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