Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Clin Chem. 2011 Feb;57(2):309-16. doi: 10.1373/clinchem.2010.153726. Epub 2010 Dec 16.
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events.
We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery.
Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A(1c), and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001).
The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.
生长分化因子 15（GDF-15）是一种应激反应细胞因子，与肥胖相关的合并症有关，如心血管疾病、炎症和癌症。GDF-15 还具有脂肪细胞因子的特性，最近被认为是心血管事件的预后生物标志物。
我们评估了血浆 GDF-15 浓度与肥胖、炎症和葡萄糖及脂质代谢参数的关系，纳入了 118 例病态肥胖患者（平均年龄 37.2[12]岁，89 名女性，29 名男性）和 30 名年龄和性别匹配的健康瘦个体。所有研究对象均接受 75g 口服葡萄糖耐量试验；28 例患者在 Roux-en-Y 胃旁路手术前和术后 1 年进行了研究。
肥胖者的血浆 GDF-15 浓度升高（P<0.001），2 型糖尿病患者的浓度最高。GDF-15 与年龄、腰高比、平均动脉血压、甘油三酯、肌酐、葡萄糖、胰岛素、C 肽、糖化血红蛋白和稳态模型评估胰岛素抵抗指数呈正相关，与口服葡萄糖胰岛素敏感性呈负相关。年龄、稳态模型评估指数、口服葡萄糖胰岛素敏感性和肌酐是 GDF-15 浓度的独立预测因素。Roux-en-Y 胃旁路手术后体重、瘦素、胰岛素和胰岛素抵抗显著降低，但 GDF-15 浓度进一步升高（P<0.001）。
与传统危险因素相比，循环 GDF-15 浓度与年龄、胰岛素抵抗和肌酐之间的关联可能解释了 GDF-15 提供的额外心血管预测信息。然而，减重手术后 GDF-15 的变化提示 GDF-15 与胰岛素抵抗之间存在间接关系。在更好地了解直接控制 GDF-15 浓度的途径之前，GDF-15 作为生物标志物的临床应用可能会受到限制。
