Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial
Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial
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DOI：
10.1530/eje-12-0466
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发表时间：
2012-11-01
影响因子：
5.8
通讯作者：
Wollert, Kai C.
中科院分区：
文献类型：
--
作者：
Kempf, Tibor;Guba-Quint, Anja;Wollert, Kai C.
目的：生长分化因子-15（GDF-15）是一种应激反应性细胞因子，在肥胖和2型糖尿病中表达增加。我们评估了GDF-15是否可以预测肥胖非糖尿病个体未来的胰岛素抵抗和血糖控制受损。在496名肥胖非糖尿病个体中，采用自动电化学发光免疫分析法测定基线和4年后的血浆GDF-15浓度（52%的男性，中位年龄48岁，中位体重指数（BMI）37.6 kg/m2）参加了XENical预防肥胖受试者糖尿病（XENDOS）试验。基线时的中位GDF-15浓度为869 ng/l（四分位距723-1064 ng/l）。GDF-15与体重、BMI、腰臀比和胰岛素抵抗（HOMA-IR）相关（均P < 0.01）。GDF-15从基线到4年的变化与体重、BMI、腰臀比和HOMA-IR的变化相关（均P < 0.05）。通过单变量分析，基线GDF-15与4年时患前驱糖尿病或糖尿病的风险相关（ln GDF-15增加1个单位的比值比（OR）为3.2; 95%置信区间（CI）：1.7-6.1; P < 0.001），在对年龄、性别、治疗分配进行多变量调整后，（奥利司他vs安慰剂）、BMI、腰臀比和基线血糖控制（OR 2.2; 95% CI：1.1-4.7; P = 0.026）。类似地，基线GDF-15与4年时的HOMA-IR独立相关（P = 0.024）。结论：在肥胖个体的大队列中对GDF-15的首次纵向研究表明，GDF-15与腹部肥胖和胰岛素抵抗相关，并且与未来的胰岛素抵抗和血糖控制异常独立相关。
Objective: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals.Design and methods: Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m(2)) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial.Results: The median GDF-15 concentration at baseline was 869 ng/l (interquartile range 723-1064 ng/l). GDF-15 was related to body weight, BMI, waist-to-hip ratio, and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) (all P < 0.01). Changes in GDF-15 from baseline to 4 years were related to changes in body weight, BMI, waist-to-hip ratio, and HOMA-IR (all P < 0.05). Baseline GDF-15 was associated with the risk to have prediabetes or diabetes at 4 years by univariate analysis (odds ratio (OR) for 1 unit increase in ln GDF-15, 3.2; 95% confidence interval (CI): 1.7-6.1; P < 0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1-4.7; P = 0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P = 0.024).Conclusions: This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.