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. 2020 Nov 23;20:174. doi: 10.1186/s12902-020-00653-x

Table 2.

Characteristics of the publications included in the meta-analysis of biomarkers in pre-diabetes

Author-year-Journal Study design Population Cases N Control N Biological sample Detection method Analytical method Covariates Metabolites
Wang-sattler et al., 2017, Mol Syst Biol [22] Cross-sectional study Augsburg and the surrounding towns and villages 340 866 serum LC-FIA-MS Multivariate logistic regression and linear regression Age, sex, BMI, PA, alcohol intake, smoking, SBP and HDL (↓) Glycine
Menni et al., 2013, Diabetes [24] Case-control study British 192 1897 plasma NA Random intercept logistic regressions analysis Age, BMI, batch effect and family relatedness

(↑) Valine, leucine, isoleucine

(↓) Citrulline

(−) proline, myristate (14:0)

Kujala et al., 2016, Front Med [25] Case-control study Older Finnish men 252 214 serum NMR platform Mann-Whitney U-test or Kruskal-Wallis test Age

(↑) Valine

(−) Leucine, isoleucine

Andersson-Hall et al., 2018, J Diabetes Res [29] 6-years follow-up study Women in Gothenburg 46 139 serum NMR Spectroscopy ANOVA and ANCOVA BMI and age

(↑) Valine, leucine, phenylalanine

(↓) Glycine

(−) Isoleucine, tyrosine

Cobb et al., 2016, Diabetes Care [44] 3-year follow-up study RISC: 19 centers in 13 countries in Europe; DMVhi: Irish RISC: 332; DMVhi: 183 RISC: 623; DMVhi; 485 plasma LC-MS/MS ROC and multiple logistic regression analyses Age, sex, and BMI

(↑) Isoleucine, leucine, valine, phenylalanine, tyrosine, 2-aminoadipic acid

(↓) Glycine

(−) Serine

Tulipani et al., 2016, Clin Chim Acta [45] Case-control study Spanish (Málaga) 12 19 serum LC-MS/MS, FIA-ESI-MS/MS the R environment, Cytoscape Age, sex, and BMI

(↑) Glutamate

(↓) Glycine

Zeng et al., 2010, Metabolomics [46] Case-control study Chinese (Changsha) 34 24 plasma GC/MS PCA and PLS-DA Age

(↑) Alanine

(−) Leucine, proline, isoleucine, phenylalanine, tyrosine, serine

Butte et al., 2015, Am J Clin Nutr [47] Case-control study Hispanic America children 450 353 plasma UPLC-MS and GC-MS PCA and mixed-effects linear regression Sex, age and Tanner stage

(↑) Alanine, glutamate, valine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, ornithine, carnitine (C0), propionylcarnitine (C3)

(↓) Asparagine, glycine, serine, citrulline

Gao et al., 2016, Nutr Metab [48] Case-control study Canadian 30 20 serum XEVO TQ MS system coupled with the Biocrates AbsoluteIDQ p180 kit PLS-DA and ANOVA BMI, age, total dietary calorie intake, and physical activity level (↑) Leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine (C3)
Kim et al., 2010, J Proteome Res [49] Case-control study South Korean 30 30 serum UPLC-QTOF-MS PCA and PLS-DA Age

(↑) L-Valine, L-tyrosine, L-leucine, L-tryptophan, propionylcarnitine (C3), hexanoyl carnitine (C6)

(↓) L-Carnitine

(−) Myristate (14:0), palmitic (C16:0)

Lee et al., 2015, Obes Res Clin Pract [50] Cohort study South Korean 64 45 plasma LC-MS/MS and FIA-MS/MS ANOVA, logistic regression and ROC curve analyses Age, BMI and waist circumference

(↑) Alanine, isoleucine, leucine, valine, phenylalanine, tyrosine, glutamate, proline, 2-amino adipic acid, carnitine (C0), propionylcarnitine (C3)

(↓) Glycine, serine, asparagine, citrulline

Mastrangelo et al., 2016, Int J Obes [51] Case-control study Spanish 50 50 serum LC-MS, GC-MS and capillary electrophoresis-mass spectrometry OPLS-DA, PCA, univariate and multivariate analyses BMI, age, fasting glucose and multiple testing (↑) Valine, isoleucine, leucine, phenylalanine, tryptophan, tyrosine, alanine, proline, C03-carnitine
Newgard et al., 2009, Cell Metab [52] Case-control study African Americans 74 67 serum MS and MS/MS PCA Age, race and sex

(↑) Valine, Aspartate/Asparagine, leucine/isoleucine, alanine, glutamate/glutamine, tyrosine, phenylalanine, proline, palmitic (C16:0), propionylcarnitine (C3), myristate (14:0)

(↓) Glycine, citrulline

(−) Serine

Ni et al., 2015, EBioMedicine [53] Longitudinal study Chinese (Shanghai) 50 12 serum UPLC-QTOF-MS OPLS-DA, ROC and logistic regression analysis, hierarchical clustering Age, sex, BMI, HOMA-IR, and fasting glucose (−) Myristate (14:0), palmitic C16:0

(↑), positive association; (↓), negative association; (−), no significant changes

Abbreviations: RISC Relationship Between Insulin Sensitivity and Cardiovascular Disease, DMVhi Diabetes Mellitus and Vascular Health Initiative, LC-MS/MS liquid chromatography coupled to tandem mass spectrometry, FIA-ESI-MS/MS flow injection electrospray ionization tandem mass spectrometry, NMR nuclear magnetic resonance spectroscopy, GC/MS gas chromatography/mass spectrometry, LC-FIA-MS liquid chromatography and flow injection analysis-mass spectrometry, UPLC-QTOF-MS ultra-performance liquid chromatograph coupled to quadruple time-of-flight mass spectrometry, ROC receiver operating characteristic, ANOVA analysis of variance, ANCOVA analysis of covariance, PCA principal component analysis, PLS-DA partial least squares-discriminant analysis, OPLS-DA orthogonal partial least squares-discriminant analysis, BMI body mass index, HOMA-IR homeostasis model assessment-insulin resistance, LPC lysophosphatidylcholine, a acyl