Supplementary Table 1. List of Metabolite Concentrations Determined Using The

Supplementary Table 1.List of metabolite concentrations determined using the BiocratesAbsoluteIDQ kit

Metabolite class / Number / Metabolite name or abbreviation / Biological relevance (selected examples)
Amino acids / 21 / Alanine, arginine, asparagine, aspartate, citrulline, glutamine, glutamate, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine / Amino acid metabolism, urea-cycle, activity of gluconeogenesis and glycolysis, insulin sensitivity, neurotransmitter metabolism,
oxidative stress
Carnitine / 1 / C0 / Energy metabolism, fatty acid transport and mitochondrial fatty acid oxidation, ketosis, oxidative stress, mitochondrial membrane damage
Acylcarnitine / 25 / C2, C3, C3:1, C4, C4:1, C5, C5:1, C6(or C4:1-DC), C6:1, C8, C9, C10, C10:1, C10:2, C12, C12:1, C14, C14:1, C14:2, C16, C16:1, C16:2, C18, C18:1, C18:2
Hydroxy- and dicarboxyacylcarnitines / 14 / C3-OH, C4-OH(or C3-DC), C5:1-DC, C5-DC(or C6-OH), C5-M-DC, C5-OH(or C3-DC-M), C7-DC, C12-DC, C14:1-OH, C14:2-OH, C16:1-OH, C16:2-OH, C16-OH, C18:1-OH
Biogenic amines / 19 / acetylornithine, asymmetric dimethylarginine, total dimethylarginine, alpha-Aminoadipic acid, carnosine, creatinine, histamine, kynurenine, methioninesulfoxide, nitrotyrosine,hydroxyproline, phenylethylamine, putrescine, sarcosine, serotonin, spermidine, spermine, taurine
Lyso-phosphatidylcholines / 14 / lysoPC a C14:0/C16:0/C16:1/C17:0/C18:0/C18:1/C18:2/ C20:3/C20:4/C26:0/C26:1/C28:0/C28:1 / Degradation of phospholipids, membrane damage, signalling cascades, fatty acid profi le
Diacyl-phosphatidylcholines / 38 / PC aa C24:0/C26:0/C28:1/C30:0/C30:2/C32:0/C32:1/C32:2/ C32:3/C34:1/C34:2/C34:3/C34:4/C36:0/C36:1/C36:2/C36:3/C36:4/C36:5/C36:6/C38:0/C38:1/C38:3/C38:4/C38:5/C38:6/C40:1/C40:2/C40:3/C40:4/C40:5/C40:6/C42:0/C42:1/C42:2/C42:4/C42:5/C42:6 / Dyslipidaemia, membrane composition and damage, fatty acid profi le, activity of desaturases
Acyl-alkyl- phosphatidylcholines / 38 / PC aeC30:0/C30:2/C32:1/C32:2/C34:0/C34:1/C34:2/C34:3/ C36:0/C36:1/C36:2/C36:3/C36:4/C36:5/C38:0/C38:1/C38:2/C38:3/C38:4/C38:5/C38:6/C40:1/C40:2/C40:3/C40:4/C40:5/C40:6/C42:0/C42:1/C42:2/C42:3/C42:4/C42:5/C44:3/C44:4/C44:5/C44:6
Sphingomyelines / 10 / SM C16:0, SM C16:1, SM C18:0, SM C18:1, SM C20:2, SM C22:3, SM C24:0, SM 24:1, SM C26:0, SM C26:1 / Signalling cascades, membrane damage (eg,
neurodegeneration)
Hydroxysphingomyelines / 5 / SM (OH) C14:1, SM (OH) C16:1, SM (OH) C22:1, SM (OH) C22:2, SM (OH) C24:1
Hexose / 1 / H1 / Carbohydrate metabolism
Total / 186

aa, acyl-acyl; ae, acyl-alkyl; a, lyso; Cx:y, where x is the number of carbons in the fatty acid side chain; y is the number of double bonds in the fatty acid side chain; DC, decarboxyl; M, methyl; OH, hydroxyl; PC, phophatidylcholine; SM, sphingomyelin.

Supplementary Table 2.Differential metabolites for the separation of groups in synovial fluid (VIP>1, P<0.05).

D1 vs D2 / M1 vs M2
Metabolites / VIP / P-value / S-plot / Metabolites / VIP / P-value / S-plot
Hexose* / 2.7 / 3.4×10-6 / -0.25 / alanine△* / 2.8 / 0.003 / -0.22
isoleucine△* / 2.3 / 1.8×10-4 / -0.21 / leucine△* / 2.6 / 0.005 / -0.19
proline△ / 2.1 / 0.002 / -0.22 / isoleucine△* / 2.6 / 0.003 / -0.20
glutamate△ / 1.8 / 0.038 / -0.17 / sarcosine△* / 2.4 / 0.012 / -0.20
leucine△* / 1.7 / 0.002 / -0.15 / Lysine* / 2.3 / 0.012 / -0.18
alanine△* / 1.7 / 0.005 / -0.11 / SM(OH)C22:1 / 2.3 / 0.019 / -0.18
valine△ / 1.6 / 0.045 / -0.09 / acetylornithine / 2.1 / 0.033 / 0.16
citrulline / 1.4 / 5.6×10-4 / 0.18 / asparagine / 2.1 / 0.024 / -0.16
PC aeC34:3△* / 1.7 / 0.015 / 0.17 / Hexose* / 2.0 / 0.001 / -0.17
arginine / 1.4 / 0.023 / 0.16 / PC aa C38:4 / 1.9 / 0.037 / -0.14
sarcosine△ / 1.5 / 0.011 / -0.09 / PC aeC34:3△* / 1.9 / 0.046 / 0.15
PC aeC36:3△* / 1.4 / 0.022 / 0.12 / #PC aa C26:0△ / 1.8 / 0.030 / 0.12
lysoPC a C26:1△ / 1.3 / 0.033 / -0.11 / PC aeC34:2△* / 1.8 / 0.047 / 0.13
lysine△* / 1.1 / 0.029 / -0.05 / SM(OH)C22:2 / 1.6 / 0.047 / -0.12
PC aeC34:2△* / 1.1 / 0.04 / 0.08

△Metabolites that could be identified both in synovial fluid and plasma.

* Common metabolites shared by D and M groups

#These metabolite concentrations below the limit of detection.

Supplementary Table 3. Differential metabolites identified in plasma between OA+MetS and OA. (VIP>1 and p<0.05)

Metabolites / VIP / P-value / S-plot / Metabolites / VIP / P-value / S-plot
PC aa C42:2 / 1.74 / 0.0003 / 0.14 / alpha-AAA / 1.29 / 0.0087 / -0.10
PC aeC32:1 / 1.7 / 0.0005 / 0.15 / PC aeC36:4 / 1.29 / 0.0092 / 0.11
Sarcosine / 1.65 / 0.0030 / -0.11 / PC aeC38:2 / 1.29 / 0.0041 / 0.12
Ala / 1.64 / 0.0080 / -0.11 / PC aeC36:1 / 1.28 / 0.0152 / 0.12
PC aeC32:2 / 1.63 / 0.0007 / 0.14 / Val / 1.28 / 0.0071 / -0.11
PC aeC42:0 / 1.6 / 0.0017 / 0.12 / PC aa C36:6 / 1.27 / 0.0092 / 0.12
PC aeC34:2 / 1.58 / 0.0031 / 0.14 / PC aeC36:5 / 1.27 / 0.0152 / 0.10
PC aa C34:2 / 1.55 / 0.0013 / 0.12 / PC aeC38:3 / 1.27 / 0.0054 / 0.12
PC aa C38:6 / 1.53 / 0.0305 / 0.08 / PC aeC38:6 / 1.27 / 0.0092 / 0.10
PC aeC36:3 / 1.53 / 0.0041 / 0.13 / PC aa C40:2 / 1.26 / 0.0118 / 0.10
PC aeC36:0 / 1.5 / 0.0009 / 0.13 / PC aa C42:1 / 1.25 / 0.0118 / 0.11
PC aeC34:3 / 1.48 / 0.0023 / 0.12 / PC aeC42:1 / 1.25 / 0.0243 / 0.10
PC aeC34:0 / 1.42 / 0.0023 / 0.13 / PC aeC40:6 / 1.24 / 0.0193 / 0.10
PC aeC34:1 / 1.42 / 0.0092 / 0.13 / PC aeC30:2 / 1.23 / 0.0152 / 0.11
PC aeC40:3 / 1.42 / 0.0054 / 0.13 / PC aeC40:2 / 1.23 / 0.0152 / 0.11
PC aa C40:3 / 1.4 / 0.0062 / 0.12 / PC aeC42:2 / 1.23 / 0.0193 / 0.11
PC aeC40:5 / 1.4 / 0.0071 / 0.11 / Kynurenine / 1.22 / 0.0167 / -0.10
lysoPC a C20:4 / 1.37 / 0.0243 / -0.10 / PC aa C42:4 / 1.21 / 0.0305 / 0.08
lysoPC a C26:1 / 1.35 / 0.0070 / -0.11 / PC aa C36:3 / 1.2 / 0.0071 / 0.11
PC aeC30:1 / 1.35 / 0.0041 / 0.12 / PC aa C32:1 / 1.15 / 0.0243 / 0.11
PC aeC36:2 / 1.34 / 0.0118 / 0.12 / PC aa C28:1 / 1.14 / 0.0243 / 0.10
PC aa C34:3 / 1.33 / 0.0092 / 0.12 / Leu / 1.12 / 0.0422 / -0.10
#PC aa C40:1 / 1.33 / 0.0071 / 0.11 / PC aa C30:0 / 1.12 / 0.0243 / 0.10
Pro / 1.33 / 0.0092 / -0.11 / lysoPC a C28:1 / 1.1 / 0.0469 / 0.11
PC aa C42:6 / 1.31 / 0.0092 / 0.11 / #PC aa C26:0 / 1.1 / 0.0193 / 0.09
PC aeC38:0 / 1.31 / 0.0017 / 0.12 / PC aa C34:4 / 1.1 / 0.0469 / 0.09
PC aeC42:3 / 1.31 / 0.0041 / 0.12 / PC aeC44:3 / 1.1 / 0.0469 / 0.13
Ile / 1.3 / 0.0152 / -0.12 / #PC aa C42:0 / 1.09 / 0.0243 / 0.09
PC aa C42:5 / 1.3 / 0.0118 / 0.10 / SM C20:2 / 1.06 / 0.0305 / 0.10
PC aeC30:0 / 1.3 / 0.0054 / 0.12 / PC aeC40:1 / 1.05 / 0.0422 / 0.09

#These metabolite concentrations below the limit of detection.

Supplementary Table 4. Differential metabolites identified in plasma between OA+diabetes and OA. (VIP>1 and p<0.05)

Metabolites / VIP / P-value / S-plot / Metabolites / VIP / P-value / S-plot
Proline / 2.3 / 1.44E-04 / -0.18 / PC aa C34:3 / 1.4 / 0.0170 / 0.08
Sarcosine / 2.2 / 2.15E-04 / -0.16 / Valine / 1.4 / 0.0102 / -0.12
Alanine / 2.2 / 3.87E-04 / -0.16 / C18:1 / 1.4 / 4.02E-04 / -0.07
Isoleucine / 2.0 / 7.89E-04 / -0.17 / lysoPC a C16:0 / 1.3 / 0.0190 / -0.08
C12 / 1.9 / 0.0115 / -0.14 / PC aeC36:3 / 1.3 / 0.0136 / 0.12
C10 / 1.7 / 0.0108 / -0.13 / C10:2 / 1.3 / 0.0083 / -0.11
C16 / 1.7 / 6.32E-04 / -0.10 / C14:2 / 1.3 / 0.0337 / -0.08
C18 / 1.6 / 4.68E-04 / -0.11 / PC aeC34:2 / 1.3 / 0.0180 / 0.12
C3-DC (C4-OH) / 1.6 / 0.0034 / -0.13 / Arginine / 1.3 / 0.0211 / 0.08
#C14 / 1.6 / 0.0015 / -0.11 / Ac-Orn / 1.3 / 0.0094 / 0.08
C16:1-OH / 1.6 / 0.0111 / -0.10 / C6 (C4:1-DC) / 1.3 / 0.0321 / -0.11
C4 / 1.6 / 0.0411 / -0.13 / total DMA / 1.2 / 0.0309 / -0.07
C16:1 / 1.5 / 0.0058 / -0.09 / C3 / 1.2 / 0.0223 / -0.12
lysoPC a C17:0 / 1.5 / 0.0053 / -0.08 / SM C20:2 / 1.2 / 0.0392 / 0.07
#C6:1 / 1.5 / 0.0261 / -0.13 / PC aa C36:3 / 1.2 / 0.0261 / 0.06
lysoPC a C18:0 / 1.5 / 0.0102 / -0.09 / PC aeC34:3 / 1.2 / 0.0223 / 0.12
Leucine / 1.5 / 0.0290 / -0.14 / #PC aa C26:0 / 1.1 / 0.0464 / 0.05
C8 / 1.5 / 0.0161 / -0.11 / alpha-AAA / 1.1 / 0.0287 / -0.07
Citrulline / 1.5 / 0.0144 / 0.09 / Lysine / 1.1 / 0.0475 / -0.09
PC aa C34:2 / 1.5 / 0.0136 / 0.06 / lysoPC a C18:1 / 1.1 / 0.0212 / -0.04

#These metabolite concentrations below the limit of detection.

Supplementary Figure 1.Schematic overview on the numbers of the different groups. (M, MetS; D, type 2 diabetes mellitus; O, obesity; H, hypertension; L, dyslipidemia; 1: positive, 2: negative)