Skip to main content

Table 2 Characteristics of the publications included in the meta-analysis of biomarkers in pre-diabetes

From: Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis

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

  1. (↑), positive association; (↓), negative association; (−), no significant changes
  2. 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