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The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples.质谱法在流行病学中分析代谢物生物标志物的应用:应用于大量生物样本的方法学和统计学考虑。
Eur J Epidemiol. 2016 Aug;31(8):717-33. doi: 10.1007/s10654-016-0166-2. Epub 2016 May 26.
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A Simultaneous Metabolic Profiling and Quantitative Multimetabolite Metabolomic Method for Human Plasma Using Gas-Chromatography Tandem Mass Spectrometry.一种使用气相色谱串联质谱法对人血浆进行同步代谢谱分析和多代谢物定量代谢组学方法
J Proteome Res. 2016 Jan 4;15(1):259-65. doi: 10.1021/acs.jproteome.5b00790. Epub 2015 Nov 30.
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Forecasting individual breast cancer risk using plasma metabolomics and biocontours.利用血浆代谢组学和生物轮廓预测个体乳腺癌风险。
Metabolomics. 2015;11(5):1376-1380. doi: 10.1007/s11306-015-0793-8. Epub 2015 Mar 10.
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Dimethylglycine Deficiency and the Development of Diabetes.二甲基甘氨酸缺乏与糖尿病的发生
Diabetes. 2015 Aug;64(8):3010-6. doi: 10.2337/db14-1863. Epub 2015 Mar 20.
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Metabolomic profile associated with insulin resistance and conversion to diabetes in the Insulin Resistance Atherosclerosis Study.胰岛素抵抗动脉粥样硬化研究中与胰岛素抵抗及糖尿病转化相关的代谢组学特征
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Towards metabolic biomarkers of insulin resistance and type 2 diabetes: progress from the metabolome.迈向胰岛素抵抗和 2 型糖尿病的代谢生物标志物:代谢组学的进展。
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The potential of novel biomarkers to improve risk prediction of type 2 diabetes.新型生物标志物提高 2 型糖尿病风险预测的潜力。
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Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach.采用非靶向代谢组学方法研究 2 型糖尿病及空腹血糖受损的生物标志物。
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Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.孟德尔随机化研究不支持循环脂联素水平降低与胰岛素抵抗和 2 型糖尿病之间存在因果关系。
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预测2型糖尿病发生的生物标志物——代谢组学能否超越现有生物标志物?

Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?

作者信息

Savolainen Otto, Fagerberg Björn, Vendelbo Lind Mads, Sandberg Ann-Sofie, Ross Alastair B, Bergström Göran

机构信息

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.

出版信息

PLoS One. 2017 Jul 10;12(7):e0177738. doi: 10.1371/journal.pone.0177738. eCollection 2017.

DOI:10.1371/journal.pone.0177738
PMID:28692646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5503163/
Abstract

AIM

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.

METHODS

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.

RESULTS

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]).

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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])。

结论

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。