Steno Diabetes Center, Gentofte, Denmark.
Diabetes Care. 2010 Jul;33(7):1567-72. doi: 10.2337/dc09-2174. Epub 2010 Mar 31.
Growth deferentiation factor-15 (GDF-15) is involved in inflammation and apoptosis. Expression is induced in the heart in response to ischemia and in atherosclerotic plaques. The aim of this study was to investigate GDF-15 levels in relation to all-cause mortality, cardiovascular mortality and morbidity, decline in glomerular filtration rate (GFR), and progression toward end-stage renal disease (ESRD).
The study was a prospective observational follow-up study including 451 type 1 diabetic patients with diabetic nephropathy (274 men, aged 42.1 +/- 0.5 years [means +/- SD], diabetes duration 28.3 +/- 8.9 years, GFR 76 +/- 33 ml/min/1.73 m(2)) and a control group of 440 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men, aged 45.4 +/- 11.5 years, duration of diabetes 27.7 +/- 10.1 years). The patients were followed for 8.1 (0.0-12.9) years (median [range]).
Among normoalbuminuric patients, GDF-15 above the median predicted an adjusted (age, systolic blood pressure [sBP], and estimated GFR) increased risk of all-cause mortality (hazard ratio [HR] 3.6 [95% CI 1.3-10.3]; P = 0.014). Among patients with diabetic nephropathy, higher (fourth quartile) versus lower (first quartile) GDF-15 levels predict all-cause mortality (covariate-adjusted [sex, age, smoking, blood pressure, A1C, cholesterol, GFR, N-terminal prohormone B-type natriuretic peptide, antihypertensive treatment, and previous cardiovascular events]; HR 4.86 [95% CI 1.37-17.30]) as well as fatal and nonfatal cardiovascular events (adjusted HR 5.59 [1.23-25.43] and 3.55 [1.08-11.64], respectively). In addition, higher GDF-15 levels predict faster decline in GFR (P < 0.001) but not development of ESRD.
Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function.
生长分化因子 15（GDF-15）参与炎症和细胞凋亡。在心脏中，它会在受到缺血和动脉粥样硬化斑块的刺激时表达。本研究的目的是探讨 GDF-15 水平与全因死亡率、心血管死亡率和发病率、肾小球滤过率（GFR）下降以及终末期肾病（ESRD）进展的关系。
本研究为前瞻性观察随访研究，纳入 451 例患有糖尿病肾病的 1 型糖尿病患者（男性 274 例，年龄 42.1±0.5 岁[平均值±标准差]，糖尿病病程 28.3±8.9 年，GFR 76±33ml/min/1.73m²）和 440 例长期患有 1 型糖尿病且持续微量白蛋白尿的患者作为对照组（男性 232 例，年龄 45.4±11.5 岁，糖尿病病程 27.7±10.1 年）。患者的中位随访时间为 8.1（0.0-12.9）年（中位数[范围]）。
在微量白蛋白尿患者中，中位数以上的 GDF-15 水平预测校正（年龄、收缩压[sBP]和估计 GFR）后全因死亡率的风险增加（风险比[HR]3.6[95%CI1.3-10.3]；P=0.014）。在糖尿病肾病患者中，较高（第四四分位）而非较低（第一四分位）的 GDF-15 水平预测全因死亡率（校正性别、年龄、吸烟、血压、A1C、胆固醇、GFR、N 末端前脑利钠肽 B 型、降压治疗和先前心血管事件的[HR4.86[95%CI1.37-17.30]）以及致命和非致命心血管事件（校正 HR5.59[1.23-25.43]和 3.55[1.08-11.64]）。此外，较高的 GDF-15 水平预示着 GFR 下降更快（P<0.001），但不会导致 ESRD 的发生。
较高的 GDF-15 水平是糖尿病肾病患者全因和心血管死亡率和发病率的预测因素。此外，较高的 GDF-15 水平与肾功能恶化更快有关。
