Background
Methods
Design and participants
Skeletal muscle inflammatory marker measurements
Gene expression analyses
Skeletal muscle metabolic intermediate measurements
Statistical analyses
Results
Clinical measures and skeletal muscle inflammatory markers
Variable | All participants (n = 102) | Rheumatoid arthritis (n = 51) | Matched controls (n = 51) |
---|---|---|---|
Age (years) | 54.2 (12.5) | 54.8 (13.2) | 53.8 (11.9) |
BMI (kg/m2) | 30.0 (6.4) | 30.3 (7.5) | 29.6 (5.1) |
Waist circumference (cm) | 94.1 (15.2) | 94.9 (16.8) | 92.9 (13.3) |
Race | |||
Caucasian | 74 (72.6%) | 36 (70.6%) | 38 (74.5%) |
African American | 27 (26.5%) | 14 (27.5%) | 13 (25.5%) |
Pacific Islander | 1 (1.0%) | 1 (2.0%) | 0 |
Gender | |||
Female | 72 (70.6%) | 36 (70.6%) | 36 (70.6%) |
Male | 30 (29.4%) | 15 (29.4%) | 15 (29.4%) |
Physical activity (kCal/day) | 557.1 (280.8) | 517.7 (279.4) | 609.1 (278.7) |
Physical activity (MET-hr/day) | 5.4 (2.6) | 4.9 (2.5) | 6.0 (2.5) |
Disease duration (months) | NA | 138.9 (136.3) | NA |
HAQ-disability index | 0.46 (0.6) | 0.68 (0.7)*
| 0.00 (0.0) |
Comorbidity index | 1.2 (1.2) | 1.6 (1.1)*
| 0.6 (0.9) |
DAS-28 mean (SD) | NA | 3.0 (1.4) | NA |
Remission (DAS-28 < 2.6) | 19 (40%) | ||
Low activity (DAS-28 2.6‒3.2) | 8 (17%) | ||
Moderate activity (DAS-28 3.2‒5.1) | 16 (33%) | ||
High activity (DAS-28 > 5.1) | 5 (10%) | ||
Rheumatoid factor positive | NA | 42/47 (89.4%) | NA |
Anti-cyclic citrullinated antibody positive | NA | 21/22 (95.6%) | NA |
Erosions present on radiographs | NA | 21/38 (55.2%) | NA |
Medication use | NA | ||
Etanercept | 10 (19.6%) | NA | |
Infliximab | 2 (3.9%) | NA | |
Adalimumab | 5 (9.8%) | NA | |
Abatacept | 5 (9.8%) | NA | |
Methotrexate | 39 (76.5%) | NA | |
Leflunomide | 1 (2.0%) | NA | |
Sulfasalazine | 0 | NA | |
Hydroxychloroquine | 10 (19.6%) | NA | |
Nonsteroidal anti-inflammatory agents | 18 (35.3%)*
| 1 (4.0%) | |
Prednisone (<5.0 mg/day) | 13 (25.5%) | NA | |
Systemic inflammation | |||
hsCRP (mg/L) | 3.0 (3.9) | 3.7 (4.9)*
| 2.4 (2.9) |
IL-1beta (pg/mL) | 0.23 (5.3) | 0.22 (4.1) | 0.17 (6.4) |
IL-6 (pg/mL) | 4.9 (2.8) | 8.9 (2.9)*
| 2.7 (1.6) |
IL-8 (pg/mL) | 8.2 (2.1) | 8.9 (1.8) | 7.5 (2.3) |
TNF-alpha (pg/mL) | 13.7 (2.3) | 19.9 (2.4)*
| 9.5 (1.7) |
IL-18 (pg/mL) | 408.3 (1.4) | 440.6 (1.3) | 379.3 (1.4) |
Adiposity and muscle tissue | |||
Abdominal total adipose area (cm2) | 427.9 (181.0) | 408.4 (199.5) | 447.3 (160.2) |
Abdominal subcutaneous adiposity (cm2) | 303.3 (143.7) | 304.5 (154.2) | 302.1 (133.9) |
Abdominal visceral adiposity (cm2) | 124.6 (93.2) | 104.0 (77.1)*
| 145.2 (103.6) |
Abdominal liver density (Hu) | 59.0 (11.6) | 59.7 (10.6) | 58.2 (12.9) |
Thigh total area (cm2) | 249.6 (65.4) | 248.8 (73.6) | 251.7 (57.1) |
Thigh total adipose area (cm2) | 250.2 (66.0) | 134.3 (65.8) | 110.9 (68.0) |
Thigh subcutaneous adiposity (cm2) | 122.6 (67.6) | 122.6 (62.7) | 113.8 (54.0) |
Thigh inter-muscular adiposity (cm2) | 11.3 (7.4) | 11.7 (6.7) | 11.0 (8.1) |
Thigh muscle area (cm2) | 119.6 (35.1) | 114.5 (37.1) | 125.4 (32.1) |
Thigh muscle density (Hu) | 54.0 (8.1) | 50.7 (6.2) | 55.4 (6.8) |
Skeletal muscle inflammatory markers | |||
IL-1β (pg/mL/mg) | 0.035 (0.084) | 0.037 (0.093) | 0.033 (0.069) |
IL-6 (pg/mL/mg) | 0.012 (0.010) | 0.014 (0.010)*
| 0.008 (0.007) |
IL-8 (pg/mL/mg) | 0.139 (0.178) | 0.169 (0.211) | 0.097 (0.106) |
TNF-α (pg/mL/mg) | 0.012 (0.015) | 0.014 (0.016) | 0.010 (0.014) |
TLR4 (pg/mL/mg) | 0.891 (0.666) | 0.859 (0.692) | 0.937 (0.625) |
Variable | Muscle IL-6 | Muscle IL-8 | Muscle TNF-α | Muscle IL-1β | Muscle TLR-4 |
---|---|---|---|---|---|
Age (years) | −0.07 | 0.05 | 0.09 | −0.09 |
−0.29
*
|
BMI (kg/m2) | 0.24 | −0.05 | −0.23 | −0.10 | −0.25 |
Disease activity (DAS28) | 0.23 |
0.30
*
| 0.14 |
0.35
*
| −0.01 |
Disability (HAQ-DI) |
0.33
*
| 0.19 | 0.09 |
0.33
*
| 0.12 |
Pain (VAS) | 0.15 | 0.17 |
0.29
*
|
0.39
*
|
0.47
*
|
Prednisone use (yes = 1) | 0.14 | −0.05 | 0.00 | 0.01 | −0.01 |
DMARD use (yes = 1) | −0.04 | −0.07 |
−0.30
| 0.21 | 0.08 |
Biologic use (yes = 1) | −0.25 |
−0.37
*
| 0.21 |
−0.33
*
| 0.01 |
Comorbidity index | 0.17 | 0.12 | 0.17 | 0.26 | −0.08 |
Plasma hsCRP (mg/L) | 0.20 | 0.07 | 0.11 | −0.03 | −0.17 |
Plasma IL-1β (pg/mL) | 0.01 | −0.07 | −0.07 | −0.14 | −0.12 |
Plasma IL-6 (pg/mL) | −0.03 | 0.11 | 0.12 | −0.01 | −0.10 |
Plasma IL-8 (pg/mL) | −0.11 | 0.06 | 0.11 | 0.14 | 0.02 |
Plasma TNF-α (pg/mL) |
−0.37
*
| −0.15 | 0.02 | −0.23 | −0.08 |
Plasma IL-18 (pg/mL) | −0.08 | −0.12 | −0.02 | −0.24 | 0.06 |
GlycA (μmol/L) |
0.41
*
|
0.38
*
| −0.06 | 0.07 | −0.21 |
HOMA | 0.11 | 0.04 | −0.06 | −0.10 | −0.07 |
Insulin sensitivity (10-5.min-1/(pmol/L)) | −0.20 | −0.19 | −0.06 | −0.09 | −0.18 |
Fasting insulin (mU/L) | 0.13 | 0.09 | −0.13 | −0.06 | −0.06 |
Visceral adiposity (cm2) | 0.11 | 0.01 | −0.28 | 0.03 | −0.23 |
Abdominal subcutaneous adiposity (cm2) | 0.21 | 0.06 | −0.19 | −0.06 | −0.19 |
Total abdominal adiposity (cm2) | 0.19 | 0.07 | −0.24 | −0.06 | −0.28 |
Thigh muscle density (Hu) | −0.04 | −0.10 | 0.06 | 0.16 |
0.28
*
|
Thigh inter-muscular adiposity (cm2) | 0.12 | 0.01 | −0.08 | −0.11 | −0.12 |
Thigh subcutaneous adiposity (cm2) |
0.31
*
| −0.07 | −0.11 | −0.09 | −0.11 |
Exercise (min/day) |
−0.40
*
|
−0.38
*
| −0.05 |
−0.38
*
| −0.11 |
Physical activity (MET h/day) |
−0.33
*
| −0.26 | 0.10 |
−0.35
*
| −0.15 |
Skeletal muscle gene expression
Pathway | Dataset genesa in pathway (n) | Total genes in pathway (n) |
Z-score |
p value |
---|---|---|---|---|
Wnt/Ca + pathway | 5 | 55 | 0 | 0.006 |
Netrin signaling | 4 | 39 | NaN | 0.008 |
Glycolysis | 3 | 24 | NaN | 0.013 |
Atherosclerosis signaling | 7 | 121 | NaN | 0.013 |
Altered T and B cell signaling in rheumatoid arthritis | 5 | 81 | NaN | 0.023 |
Methionine degradation to homocysteine | 2 | 16 | NaN | 0.043 |
PI3K signaling in B lymphocytes | 6 | 123 | −0.816 | 0.043 |
April mediated signaling | 3 | 38 | NaN | 0.044 |
B cell activating factor signaling | 3 | 40 | NaN | 0.049 |
Gene ID | Gene name | RA vs. CONTROL | |
---|---|---|---|
Fold change |
p value | ||
BTF3 | Basic transcription factor 3 | 1.11 | 0.003 |
CTDP1 | CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) phosphatase, subunit 1 | −1.04 | 0.006 |
DDRGK1 | DDRGK domain containing 1 | −1.07 | 0.02 |
DIO1 | Deiodinase, iodothyronine, type I | 1.03 | 0.005 |
EDARADD | EDAR-associated death domain | −1.06 | 0.007 |
EIF2AK1 | Eukaryotic translation initiation factor 2-alpha kinase 1 | 1.05 | 0.007 |
FKBPL | FK506 binding protein like | −1.06 | 0.003 |
GUCY2D | Guanylate cyclase 2D, membrane (retina-specific) | −1.04 | 0.004 |
IFT57 | Intraflagellar transport 57 | 1.04 | 0.01 |
IRAK1BP1 | Interleukin-1 receptor-associated kinase 1 binding protein 1 | 1.02 | 0.02 |
KMT2C | Lysine (K)-specific methyltransferase 2C | 1.03 | 0.01 |
LAMB1 | Laminin, beta 1 | 1.11 | 0.02 |
MAZ | MYC-associated zinc finger protein (purine-binding transcription factor) | −1.03 | 0.008 |
MYL4 | Myosin, light chain 4, alkali; atrial, embryonic | 1.02 | 0.01 |
NFkB2 | Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p52/p100) | −1.06 | 0.003 |
NOP14 | NOP14 nucleolar protein | −1.08 | 0.008 |
OGG1 | 8-Oxoguanine DNA glycosylase | 1.03 | 0.002 |
PKD2 | Polycystic kidney disease 2 (autosomal dominant) | 1.05 | 0.02 |
POLR2J2/POLR2J3 | Polymerase (RNA) II (DNA directed) polypeptide J3 | 1.08 | 0.004 |
PPP4R4 | Protein phosphatase 4, regulatory subunit 4 | 1.03 | 0.006 |
RHOH | Ras homolog family member H | −1.06 | 0.002 |
S100B | S100 calcium binding protein B | 1.02 | 0.02 |
SCIN | Scinderin | 1.04 | 0.001 |
STC2 | Stanniocalcin 2 | 1.04 | 0.008 |
TAF1 | TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 250 kDa | 1.04 | 0.02 |
TNFRSF12A | Tumor necrosis factor receptor superfamily, member 12A; TNF-like weak inducer of apoptosis (TWEAK) receptor | 1.24 | 0.01 |
TNFRSF18 | Tumor necrosis factor receptor superfamily, member 18 | −1.02 | 0.005 |
Gene ID | Gene name and description | Fold change |
p value |
---|---|---|---|
Upregulated in RA
| |||
OTUD1 | OUT deubiquitinase 1: removes ubiquitin molecules with probable signaling regulatory role | 1.50 | 0.035 |
FEZ2a
| 1.40 | 0.005 | |
PITX1a
| Paired-like homeodomain 1: promotes muscle atrophy [34] | 1.37 | 0.046 |
RNU4ATAC | 1.36 | 0.045 | |
ABRAa
| Actin binding Rho activating protein: promotes myoblast differentiation and myotube maturation [24] | 1.33 | 0.031 |
RCAN1a
| Regulator of calcineurin 1: regulates fiber type patterning during differentiation | 1.32 | 0.019 |
CITED2a
| 1.32 | 0.027 | |
VGLL2a
| Vestigial-like family member 2: expressed in myotubes [27] | 1.30 | 0.035 |
MYF6a
| Myogenic factor 6 (herculin): promotes myoblast terminal differentiation [29] | 1.27 | 0.033 |
RPL36AL | Ribosomal protein L36a-like: ribosomal protein with ability to terminate translation in certain situations [38] | 1.27 | 0.011 |
Downregulated in RA
| |||
FBP2b
| −1.42 | 0.013 | |
MYLK4a
| Myosin light chain kinase family, member 4: reduced expression associated with cardiomyopathies [42] | −1.37 | 0.024 |
ZFP36ac
| ZFP36 ring finger protein; encodes tristetraprolin (TTP): reduces inflammation and prevents satellite cell activation [20] | −1.36 | 0.023 |
DDIT4a
| DNA damage-inducible transcript 4; also known as protein regulated in development and damage response 1 (REDD-1): promotes autophagy, with reduced expression associated with exercise intolerance [43] | −1.34 | 0.023 |
MIDNb
| −1.32 | 0.017 | |
SLC2A5b
| Solute carrier family 2 (facilitated glucose/fructose transporter), member 5: performs facilitative fructose uptake into muscle [46] | −1.31 | 0.041 |
SLC25A25b
| −1.30 | 0.013 | |
RRADa
| Ras-related associated with diabetes: increases myoblast proliferation and promotes myotube formation [30] | −1.30 | 0.044 |
ZBTB16bc
| −1.27 | 0.050 | |
SMTNL2 | Smoothelin-like 2: associated with myotube formation [50] | −1.22 | 0.008 |
Gene ID | Gene name | Rheumatoid arthritis vs. control | |
---|---|---|---|
Fold change |
p value | ||
Ubiquitin-proteasome pathway
| |||
MuRF1 | Muscle RING-finger protein-1 | −1.02 | 0.25 |
MuRF2 | Muscle-specific RING finger-2 | −1.01 | 0.47 |
FbxO32 | F-box protein 32 | 1.02 | 0.88 |
FbxO40 | F-box protein 40 | −1.03 | 0.37 |
Autophagy-lysozyme pathway
| |||
Atg5 | Autophagy related 5 | −1.01 | 0.77 |
Atg7 | Autophagy related 7 | −1.09 | 0.13 |
NAF1 | Nuclear assembly factor 1 ribonucleoprotein | −1.03 | 0.12 |
Lamp2 | Lysosomal-associated membrane protein 2 | −1.03 | 0.65 |
IGF1/Akt signaling pathway
| |||
IGF1 | Insulin-like growth factor 1 | 1.00 | 0.85 |
Akt1 | V-Akt murine thymoma viral oncogene homolog 1 | 1.00 | 0.92 |
Akt2 | V-Akt murine thymoma viral oncogene homolog 2 | −1.04 | 0.41 |
Rptor | Regulatory associated protein of MTOR, complex 1 | 1.02 | 0.45 |
Rictor | RPTOR independent companion of MTOR, complex 2 | 1.01 | 0.54 |
FoxO1 | Forkhead box O1 | −1.07 | 0.34 |
FoxO3 | Forkhead box O3 | −1.09 | 0.39 |
TGFbeta/Myostatin signaling pathway
| |||
ActRIIIB | ARP3 actin-related protein 3 homolog B | 1.02 | 0.69 |
FST | Follistatin | −1.02 | 0.30 |
NFkB signaling pathways
| |||
IKBKB | Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase beta | −1.08 | 0.17 |
IKBKAP | Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein | 1.001 | 0.43 |
TRAF6 | TNF receptor-associated factor 6, E3 ubiquitin protein ligase | 1.02 | 0.37 |
TRADD | TNFRSF1A-associated via death domain | −1.02 | 0.46 |
Bcl3 | B-Cell CLL/lymphoma 3 | −1.02 | 0.32 |
TRAF2 | TNF receptor-associated factor 2 | −1.00 | 0.95 |
TRAF5 | TNF receptor-associated factor 5 | 1.01 | 0.37 |
MAPK8 | Mitogen-activated protein kinase 8 | −1.01 | 0.32 |
NFkB1 | Homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (p105/p50) | −1.00 | 0.97 |
NFkB2 | Homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B cells 2 (p52/p100) | −1.06 | 0.003 |
Skeletal muscle metabolic intermediates
Rheumatoid arthririts (n = 51) | Controls (n = 50) | |||
---|---|---|---|---|
Mean | SD | Mean | SD | |
Amino acids
| ||||
Glycine | 1012.669 | 304.568 | 1042.875 | 360.089 |
Alanine | 2781.241 | 876.247 | 2735.464 | 820.802 |
Serine | 773.987 | 190.246 | 777.726 | 286.455 |
Proline | 502.861 | 179.5 | 528.023 | 222.984 |
Valine | 291.82 | 75.004 | 300.739 | 99.003 |
Leucine/isoleucine | 659.544 | 197.996 | 663.116 | 233.404 |
Methionine | 54.167 | 14.36 | 55.372 | 17.48 |
Histidine | 488.821 | 164.605 | 548.187 | 276.048 |
Phenylalanine | 77.739 | 22.414 | 80.155 | 27.759 |
Tyrosine | 80.962 | 23.249 | 88.815 | 32.052 |
Aspartate/asparagine | 100.518 | 62.088 | 144.672 | 198.704 |
Glutamate/glutamine | 2096.524 | 658.272 | 2359.04 | 878.482 |
Ornithine | 212.338 | 85.775 | 184.849 | 69.873 |
Citrulline | 69.446 | 39.718 | 75.05 | 50.441 |
Arginine | 431.024 | 182.215 | 394.565 | 149.594 |
Organic acids
| ||||
Lactate | 22862.683 | 9246.29 | 20956.576 | 8926.553 |
Pyruvate | 1168.544* | 604.675 | 803.474 | 539.098 |
Succinate | 48.143 | 35.538 | 41.793 | 29.968 |
Fumarate | 70.313 | 26.403 | 62.708 | 25.253 |
Malate | 521.019 | 205.905 | 476.648 | 198.079 |
alphaKetoglutarate | 144.24 | 143.952 | 113.438 | 118.669 |
Citrate | 41.677 | 33.591 | 36.853 | 24.096 |
Acylcarnitines
| ||||
Free carnitine: C0 | 3369.034 | 1006.646 | 3631.978 | 1243.598 |
C2 | 455.175 | 288.39 | 485.702 | 312.966 |
C3 | 5.206 | 2.024 | 5.019 | 2.018 |
C4/Ci4 | 3.541 | 4.994 | 3.008 | 2.594 |
C5:1 | 1.033 | 0.397 | 1.03 | 0.41 |
C5 | 1.667 | 1.15 | 2.246 | 5.666 |
C4OH | 2.789 | 2.231 | 2.378 | 1.778 |
C6 | 3.58 | 3.882 | 2.956 | 2.855 |
C5OH | 0.676 | 0.363 | 0.65 | 0.343 |
C3DC | 0.793 | 0.356 | 0.809 | 0.292 |
C4DC/Ci4DC | 2.439 | 1.424 | 2.547 | 1.192 |
C8:1 | 0.531 | 0.328 | 0.532 | 0.252 |
C8 | 0.942 | 0.904 | 0.826 | 0.694 |
C5DC | 1.528 | 1.043 | 1.43 | 0.727 |
C8:1OH/C6:1 DC | 0.216 | 0.129 | 0.204 | 0.123 |
C6DC/C8OH | 0.353 | 0.239 | 0.388 | 0.226 |
C10:3 | 0.067 | 0.047 | 0.067 | 0.034 |
C10:2 | 0.05 | 0.03 | 0.063 | 0.041 |
C10:1 | 0.261 | 0.253 | 0.239 | 0.164 |
C10 | 0.655 | 0.6 | 0.58 | 0.48 |
C7DC | 0.108 | 0.079 | 0.088 | 0.049 |
C8:1 DC | 0.087 | 0.073 | 0.093 | 0.051 |
C10OH:C8DC | 0.305 | 0.253 | 0.31 | 0.21 |
C12:2 | 0.052 | 0.034 | 0.052 | 0.035 |
C12:1 | 0.364 | 0.281 | 0.366 | 0.287 |
C12 | 1.359 | 1.073 | 1.31 | 1.125 |
C12:2OH/C10:2 DC | 0.075 | 0.045 | 0.064 | 0.04 |
C12:1OH/C10:1 DC | 0.224 | 0.178 | 0.202 | 0.114 |
C12OH/C10DC | 0.441 | 0.472 | 0.417 | 0.382 |
C14:3 | 0.078 | 0.052 | 0.073 | 0.054 |
C14:2 | 1.126 | 1.025 | 0.902 | 0.83 |
C14:1 | 2.726 | 2.354 | 2.449 | 2.232 |
C14 | 4.156 | 3.277 | 3.781 | 3.373 |
C14:3OH/C12:3 DC | 0.032 | 0.025 | 0.028 | 0.022 |
C14:2OH/C12:2 DC | 0.174 | 0.121 | 0.143 | 0.081 |
C14:1OH/C12:1 DC | 0.704 | 0.538 | 0.701 | 0.431 |
C14OH/C12DC | 0.502 | 0.525 | 0.487 | 0.381 |
C16:3 | 0.198 | 0.164 | 0.157 | 0.103 |
C16:2 | 1.533 | 1.201 | 1.199 | 0.948 |
C16:1 | 6.736 | 5.227 | 5.751 | 3.973 |
C16 | 20.041 | 15.253 | 17.878 | 12.497 |
C16:3OH/C14:3-DC | 0.053 | 0.038 | 0.045 | 0.024 |
C16:2OH/C14:2 DC | 0.477 | 0.336 | 0.412 | 0.248 |
C16:1OH/C14:1 DC | 1.306 | 1.077 | 1.256 | 0.834 |
C16OH/C14DC | 1.18 | 1.265 | 1.229 | 1.059 |
C18:3 | 1.463 | 0.982 | 1.354 | 0.925 |
C18:2 | 20.561 | 15.909 | 17.722 | 13.495 |
C18:1 | 46.521 | 37.117 | 40.451 | 28.311 |
C18 | 11.278 | 8.401 | 10.817 | 8.203 |
C18:3OH/C16:3 DC | 0.186 | 0.158 | 0.168 | 0.101 |
C18:2OH/C16:2 DC | 1.357 | 1.235 | 1.323 | 1.177 |
C18:1OH/C16:1 DC | 2.683 | 2.889 | 2.844 | 2.749 |
C18OH/C16DC | 0.695 | 0.68 | 0.732 | 0.523 |
C20:4 | 2.023 | 1.801 | 1.778 | 1.872 |
C20:3 | 0.63 | 0.597 | 0.57 | 0.431 |
C20:2 | 0.308 | 0.271 | 0.261 | 0.164 |
C20:1 | 0.554 | 0.484 | 0.485 | 0.409 |
C20 | 0.369 | 0.4 | 0.329 | 0.308 |
C20:3OH/C18:3 DC | 0.075 | 0.059 | 0.074 | 0.056 |
C20:2OH/C18:2 DC | 0.053 | 0.034 | 0.05 | 0.03 |
C20:1OH/C18:1 DC | 0.071 | 0.062 | 0.062 | 0.046 |
C20OHC18DC/C22:6 | 0.212 | 0.248 | 0.198 | 0.206 |
C22:5 | 0.264 | 0.299 | 0.247 | 0.277 |
C22:4 | 0.241 | 0.279 | 0.193 | 0.158 |
C22:3 | 0.064 | 0.057 | 0.056 | 0.044 |
C22:2 | 0.051 | 0.035 | 0.044 | 0.025 |
C22:1 | 0.069 | 0.05 | 0.065 | 0.038 |
C22 | 0.059 | 0.049 | 0.062 | 0.046 |
Disease activity | Disability | Pain | Exercise (min/d) | Physical activity (MET h/d) | |
---|---|---|---|---|---|
Amino acids
| |||||
Glycine | 0.33b
| 0.50a
| 0.23 | 0.11 | 0.02 |
Alanine | -0.31b
| 0.03 | -0.01 | 0.11 | 0.08 |
Serine | 0.31b
| 0.20 | 0.17 | -0.03 | -0.01 |
Proline | 0.20 | 0.36a
| 0.09 | 0.05 | 0.08 |
Valine | 0.12 | 0.11 | -0.04 | 0.05 | -0.01 |
Leucine/isoleucine | 0.09 | 0.18 | -0.01 | -0.08 | -0.16 |
Methionine | 0.07 | 0.16 | -0.17 | -0.01 | -0.04 |
Histidine | -0.08 | -0.02 | -0.12 | 0.23 | 0.19 |
Phenylalanine | -0.06 | -0.04 | -0.21 | 0.06 | 0.04 |
Tyrosine | -0.06 | 0.08 | -0.13 | 0.13 | 0.14 |
Aspartate/asparagine | 0.34b
| 0.36a
| 0.20 | -0.13 | -0.12 |
Glutamate/glutamine | 0.20 | 0.24 | 0.06 | -0.12 | -0.04 |
Ornithine | 0.32b
| 0.39a
| 0.14 | -0.21 | -0.20 |
Citrulline | 0.08 | 0.21 | 0.13 | -0.02 | 0.13 |
Arginine | 0.27 | 0.45a
| 0.24 | -0.26 | -0.27 |
Organic acids
| |||||
Lactate | -0.09 | -0.18 | -0.06 | -0.09 | -0.12 |
Pyruvate | -0.22 | -0.22 | -0.21 | 0.16 | 0.05 |
Succinate | 0.03 | -0.01 | 0.15 | -0.06 | -0.12 |
Fumarate | -0.34b
| -0.24 | -0.15 | 0.05 | -0.01 |
Malate | -0.28 | -0.14 | 0.04 | -0.01 | -0.07 |
alphaKetoglutarate | -0.22 | -0.03 | -0.03 | 0.27 | 0.18 |
Citrate | 0.17 | 0.23 | 0.29 | 0.05 | 0.14 |
Acylcarnitines
| |||||
Free carnitine: C0 | -0.10 | 0.19 | 0.10 | 0.04 | 0.08 |
C2 | -0.07 | 0.08 | 0.07 | -0.22 | -0.02 |
C3 | -0.05 | 0.10 | -0.01 | 0.10 | 0.00 |
C4/Ci4 | -0.02 | -0.13 | -0.20 | 0.09 | 0.16 |
C5:1 | 0.15 | 0.09 | 0.06 | -0.10 | 0.05 |
C5 | 0.01 | 0.05 | -0.24 | 0.14 | 0.10 |
C4OH | 0.11 | 0.09 | 0.11 | -0.11 | -0.04 |
C6 | 0.05 | -0.10 | -0.24 | 0.30 | 0.29 |
C5OH | -0.24 | 0.04 | 0.14 | 0.14 | 0.25 |
C3DC | -0.17 | 0.13 | 0.03 | -0.02 | 0.10 |
C4DC/Ci4DC | 0.02 | 0.28b
| 0.05 | -0.32b
| -0.23 |
C8:1 | -0.10 | -0.05 | -0.15 | -0.07 | 0.00 |
C8 | 0.01 | -0.11 | -0.13 | 0.16 | 0.13 |
C5DC | 0.19 | 0.20 | 0.03 | -0.12 | -0.11 |
C8:1OH/C6:1 DC | 0.11 | 0.21 | 0.12 | -0.05 | -0.11 |
C6DC/C8OH | -0.02 | 0.03 | -0.10 | 0.08 | 0.11 |
C10:3 | 0.02 | 0.15 | 0.15 | -0.10 | -0.09 |
C10:2 | 0.00 | 0.06 | -0.05 | -0.14 | -0.20 |
C10:1 | -0.09 | -0.09 | -0.08 | 0.19 | 0.11 |
C10 | -0.05 | -0.12 | -0.13 | 0.15 | 0.14 |
C7DC | 0.04 | 0.13 | 0.06 | -0.20 | -0.20 |
C8:1 DC | -0.17 | -0.03 | -0.13 | -0.06 | -0.09 |
C10OH:C8DC | -0.08 | 0.00 | -0.15 | 0.06 | 0.07 |
C12:2 | 0.04 | -0.01 | -0.08 | -0.24 | -0.26 |
C12:1 | -0.14 | -0.12 | -0.13 | 0.14 | 0.12 |
C12 | -0.20 | -0.22 | -0.19 | 0.20 | 0.19 |
C12:2OH/C10:2 DC | -0.19 | -0.03 | -0.14 | 0.06 | 0.00 |
C12:1OH/C10:1 DC | -0.19 | -0.07 | -0.16 | 0.15 | 0.18 |
C12OH/C10DC | -0.16 | 0.03 | -0.13 | 0.13 | 0.14 |
C14:3 | -0.14 | -0.09 | -0.15 | 0.19 | 0.20 |
C14:2 | -0.22 | -0.17 | -0.22 | 0.27 | 0.26 |
C14:1 | -0.18 | -0.16 | -0.17 | 0.21 | 0.21 |
C14 | -0.25 | -0.21 | -0.26 | 0.24 | 0.22 |
C14:3OH/C12:3 DC | -0.05 | 0.08 | -0.01 | -0.03 | 0.12 |
C14:2OH/C12:2 DC | -0.12 | -0.03 | -0.20 | 0.04 | 0.03 |
C14:1OH/C12:1 DC | -0.24 | -0.11 | -0.19 | 0.14 | 0.17 |
C14OH/C12DC | -0.13 | 0.03 | -0.14 | 0.16 | 0.17 |
C16:3 | -0.28 | -0.19 | -0.22 | 0.26 | 0.27 |
C16:2 | -0.34b
| -0.26 | -0.26 | 0.35a
| 0.33b
|
C16:1 | -0.28 | -0.22 | -0.17 | 0.22 | 0.18 |
C16 | -0.27 | -0.20 | -0.19 | 0.17 | 0.18 |
C16:3OH/C14:3-DC | -0.16 | -0.10 | -0.03 | 0.11 | 0.19 |
C16:2OH/C14:2 DC | -0.26 | -0.16 | -0.19 | 0.12 | 0.10 |
C16:1OH/C14:1 DC | -0.25 | -0.09 | -0.21 | 0.10 | 0.12 |
C16OH/C14DC | -0.17 | 0.04 | -0.08 | 0.10 | 0.12 |
C18:3 | -0.43a
| -0.36a
| -0.19 | 0.20 | 0.19 |
C18:2 | -0.40a
| -0.39a
| -0.19 | 0.23 | 0.18 |
C18:1 | -0.33b
| -0.32b
| -0.15 | 0.15 | 0.13 |
C18 | -0.21 | -0.13 | -0.12 | 0.06 | 0.09 |
C18:3OH/C16:3 DC | -0.29 | -0.06 | -0.02 | 0.18 | 0.18 |
C18:2OH/C16:2 DC | -0.31b
| -0.06 | -0.08 | 0.12 | 0.14 |
C18:1OH/C16:1 DC | -0.22 | 0.02 | -0.04 | 0.06 | 0.07 |
C18OH/C16DC | -0.18 | 0.03 | -0.08 | -0.03 | 0.00 |
C20:4 | -0.28 | -0.30b
| -0.12 | 0.26 | 0.27 |
C20:3 | -0.29b
| -0.37a
| -0.11 | 0.18 | 0.17 |
C20:2 | -0.25 | -0.20 | -0.14 | 0.11 | 0.14 |
C20:1 | -0.25 | -0.16 | -0.11 | 0.07 | 0.08 |
C20 | -0.18 | -0.04 | -0.09 | -0.02 | -0.01 |
C20:3OH/C18:3 DC | 0.09 | 0.21 | -0.01 | -0.14 | -0.08 |
C20:2OH/C18:2 DC | -0.16 | -0.15 | 0.06 | -0.14 | -0.14 |
C20:1OH/C18:1 DC | -0.03 | 0.18 | -0.03 | 0.00 | 0.04 |
C20OHC18DC/C22:6 | -0.16 | 0.00 | -0.09 | -0.05 | -0.08 |
C22:5 | -0.28 | -0.20 | -0.14 | 0.15 | 0.09 |
C22:4 | -0.22 | -0.24 | -0.06 | 0.07 | 0.09 |
C22:3 | -0.03 | -0.11 | 0.01 | -0.06 | -0.03 |
C22:2 | 0.13 | -0.01 | -0.06 | 0.09 | 0.24 |
C22:1 | 0.06 | 0.01 | -0.12 | 0.28 | 0.36 |
C22 | -0.02 | -0.06 | 0.00 | 0.03 | 0.10 |