Journal of Diabetes Research

Review Article

The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review

Table 1

General population characteristics of included studies in this systematic review.
Study itemYearNumberTypeMean ageBMI (kg/m2)HOMA-IRDetection platform
Chen et al. [29]2016213Cohort studyFDM:
53.78 ± 1.75
Control:
38.51 ± 0.95		FDM:
25.53 ± 0.50
Control:
24.63 ± 0.27		FDM:
2.13 ± 0.61
Control:
1.67 ± 0.30		UPLC-TQ-MS
Chen et al. [29]2016216Observational study52.81 ± 0.71Obese:
27.26 ± 0.25
Lean:
20.48 ± 0.07		Obese:
2.08 ± 0.54
Lean:
1.11 ± 0.17		UPLC-TQ-MS
Lee et al. [20]2016685Cohort study54 (47–62)LT:
26.9 ± 5.0;
MT: 28.5 ± 5.6;
UT: 29.7 ± 5.4		LT:
2.19 ± 0.39
MT:
1.64 ± 0.6
UT:
1.27 ± 0.25		MS/MS
Takashina et al. [34]201683Observational study34.0 ± 5.7Obese:
26.7 ± 2.3
Nonobese:
21.9 ± 1.8		Obese:
2.1 ± 1.6
Nonobese:
1.1 ± 0.5		HPLC
Bogl et al. [25]2016286Observational study28.7 ± 0.225.4 ± 0.31.4 ± 0.1NMR
Boulet et al. [32] 201659Observational study47 ± 5.0Lean:
23.2 ± 1.3
Overweight:
27.0 ± 1.3
Obese:
34.0 ± 3.3		Lean:
1.9 ± 1.4
Overweight:
1.7 ± 0.9
Obese:
2.6 ± 1.0		ESI-LC-MS/MS,
ESI-MS/MS
Tillin et al. [36]20152286Cohort studyEuropean:
52.9 ± 7.3
South Asian 50.6 ± 7		European:
25.65 ± 0.73
South Asian
25.46 ± 0.67 		European:
1.71 ± 0.26
South Asian
2.43 ± 0.35		NMR
Yamada et al. [35]201594Observational study40.1 ± 9.622.7 ± 3.91.12 ± 0.72LC/MC
Liu et al. [31]201530Observational study20.5 ± 1.8Obese:
32.62 ± 2.70
Control:
20.77 ± 1.25		Obese:
1.55 ± 0.12
Control:
1.25 ± 0.11		GC/MS, UPLC-TQ-MS
Badoud et al. [33]201430Observational studyLH:
51 ± 3
MHO:
50 ± 4
MUO:
48 ± 2		LH:
22.1 ± 0.6
MHO:
30.6 ± 1.1
MUO:
33.0 ± 1.9		LH:
0.65 ± 0.28
MHO:
1.18 ± 0.16
MUO:
2.19 ± 0.42		GC-MS,
CE-MS
Xie et al. [30]2014211Cohort studyObese:
46.8 ± 6.9
Lean:
45.9 ± 7.2		Obese:
26.7 ± 1.25
Lean:
20.6 ± 0.52		Obese:
1.97 ± 0.83
Lean:
1.11 ± 0.52		UPLC-QTOFMS; GC-TOFMS
Xie et al. [30]2014105Cohort studyObese:
47.0 ± 8.0
Lean:
49.9 ± 8.3		Obese:
27.1 ± 1.2
Lean:
18.8 ± 0.7		Obese:
2.20 ± 0.73
Lean:
1.31 ± 0.5		UPLC-QTOFMS; GC-TOFMS
Serralde-Zúñiga et al. [39]2014115Observational studyNon-IR
41 ± 10
IR:
39 ± 11		Non-IR:
29.8 ± 10.9
IR:
44.2 ± 11.8		Non-IR:
1.6 ± 0.6
IR:
5.4 ± 3.2		N/A
Wiklund et al. [26]201478Observational studyMHO:
39.7 ± 7
MetS:
44 ± 6		MHO:
28.9 ± 3.2
MetS:
30.6 ± 3.4		MHO:
1.6 ± 1.0
MetS:
2.3 ± 0.9		NMR
Batch et al. [21]20131872Observational study59.49 ± 11.830.05 ± 6.442.24 ± 1.87MS/MS
Floegel et al. [15]20132282Cohort study49.5 ± 8.926.1 ± 0.091.6 ± 0.4FIA-MS/MS
Xu et al. [22]2013734Cohort study51.2 ± 932.65 ± 3.92.36 ± 0.36N/A
Naukkarinen et al. [27] 201432Observational study27.4 ± 1.0
Obese:
30.4 ± 1.3
Nonobese:
24.75 ± 1.3		Obese:
2.95 ± 0.5
Nonobese:
1.35 ± 0.3		GC-TOFMS
Cheng et al. [23]20121015Observational study56 ± 928.3 ± 5.02.5 ± 2.2LC/MS
Würtz et al. [28]20127098Observational study31 ± 3Men:
31.2 ± 2.6
Women:
31.2 ± 2.8		Men:
0.98 ± 0.09
Women:
0.92 ± 0.08		NMR
Shah et al. [24] 2012500Cohort study55.9 ± 8.733.9 ± 4.72.45 ± 0.5MS/MS
Wang et al. [14] 20112422Cohort studyCase:
56 ± 9
Con: 57 ± 8		Case:
30.5 ± 5
Control:
30.0 ± 5.5		Case:
3.5 ± 2.6
Control:
3.1 ± 2.3		LC-MS
Kim et al. [37]201060Observational study39.55 ± 1.24Obese:
28.9 ± 0.2
Nonobese:
20.9 ± 0.14		Case:
3.34 ± 0.3
Control:
1.72 ± 0.11		UPLC-Q-TOF
MS
Newgard et al. [12]2009141Observational study51 ± 9Obese:
36.6 ± 1.33
Lean:
23.2 ± 0.33		Obese:
5.73 ± 0.74
Lean:
2.61 ± 0.22		MS/MS,
GC/MS
Tai et al. [38] 2010263Observational study49.25 ± 10.6Chinese:
24.2 ± 2
India Asian:
24.7 ± 2.1		Chinese:
1.8 ± 0.8
India Asian:
2.63 ± 2		MS/MS,
GC/MS
Note: BMI: body mass index; HOMA-IR: homeostasis model of assessment for insulin resistance index; BCAA: branched-chain amino acids; LH: lean healthy; MHO: metabolically healthy obese; MUO: metabolically unhealthy obese; FDM: future diabetes development; LT: lowest third of BCAA; MT: middle third of BCAA; UT: upper third of BCAA; MetS: metabolic syndrome; IR: insulin resistance; non-IR: noninsulin resistance; N/A: not applicable; UPLC-TQ-MS: ultraperformance liquid chromatography triple quadruple mass spectrometry; MS/MS: tandem mass spectrometry; HPLC: ultraperformance liquid chromatography; NMR: nuclear magnetic resonance; ESI-LC-MS/MS: liquid chromatography-electrospray ionization mass spectrometry; ESI-MS/MS: electrospray ionization mass spectrometry; LC/MC: liquid chromatography/mass spectrometry; GC/MS: gas chromatography-mass spectrometry; CE-MS: capillary electrophoresis-mass spectrometry; GC-TOFMS: gas chromatography/time-of-flight mass spectrometry; FIA-MS/MS: flow injection analysis tandem mass spectrometry; study I; study II for validation; data for insulin sensitivity.