Savolainen Otto, Fagerberg Björn, Vendelbo Lind Mads, Sandberg Ann-Sofie, Ross Alastair B, Bergström Göran
Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Wallenberg Laboratory for Cardiovascular Research at the Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
PLoS One. 2017 Jul 10;12(7):e0177738. doi: 10.1371/journal.pone.0177738. eCollection 2017.
The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers.
Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years follow-up. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D.
Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and 0.808 [0.749-0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577-0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]).
Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model.
确定代谢组学是否可用于构建2型糖尿病(T2D)风险预测模型,该模型在预测T2D方面优于当前的风险标志物。
在一项基于64岁白人女性筛查样本(n = 629)的巢式病例对照研究中,采用气相色谱 - 串联质谱代谢组学技术。在基线时采集的血浆中鉴定T2D的候选代谢标志物,并在5.5年随访期间发生的69例新发病例中测试预测糖尿病的能力。代谢组学结果被用作独立的预测模型,并与已建立的T2D预测生物标志物相结合,构建八个T2D预测模型,根据它们预测T2D的敏感性和选择性相互比较。
单独的T2D既定标志物(空腹血糖受损、糖耐量受损、胰岛素抵抗(HOMA)、吸烟、血清脂联素)以及与代谢组学相结合时,曲线下面积(AUC)最大(分别为0.794(95%置信区间[0.738 - 0.850])和0.808 [0.749 - 0.867]),基于九种空腹血浆标志物的独立代谢组学模型预测能力较低(0.657 [0.577 - 0.736])。基于非血液指标的预测为0.638 [0.565 - 0.711])。
在该人群中,既定的T2D风险测量方法仍然是T2D风险的最佳预测指标。使用代谢组学检测到的其他标志物可能与这些指标相关,因为它们在联合模型中并未增强整体预测效果。