Introduction
Methods
Study population
Untargeted LC-MS metabolomics
Data preprocessing
Statistical analysis
Identification of metabolites
Results
Characteristic | Cases (n = 503) | Matched controls (n = 503) | p value for difference |
---|---|---|---|
Mena | 44.5 | 44.5 | |
Age, yearsa | 50.2 (7.9) | 50.1 (8.0) | |
Fasting glucose, mmol/l | 6.0 (0.9) | 5.5 (1.1) | <0.0001 |
2 h-PG, mmol/l | 8.3 (2.8) | 6.5 (1.6) | <0.0001 |
BMI, kg/m2 | 29.5 (4.9) | 25.5 (3.8) | <0.0001 |
HOMA-IRb | 1.7 (1.1) | 0.9 (0.7) | <0.0001 |
HOMA-%Bb | 101.5 (72.9) | 74.5 (27.7) | <0.0001 |
Triacylglycerols, mmol/l | 2.0 (1.3) | 1.4 (0.7) | <0.0001 |
Total cholesterol, mmol/l | 5.9 (1.2) | 5.7 (1.1) | <0.0001 |
Systolic BP, mmHg | 138 (18.1) | 128 (17.2) | <0.0001 |
Diastolic BP, mmHg | 85 (10.4) | 80 (9.7) | <0.0001 |
Total energy intake, kJ/day | 7186.0 (2551.2) | 7282.2 (2594.1) | 0.6 |
Dietary fibre, g/day | 18.9 (7.4) | 19.5 (8.2) | 0.3 |
Whole grains, g/day | 72.2 (36.5) | 74.4 (39.6) | 0.5 |
Fat, g/day | 68.2 (26.0) | 64.3 (27.7) | 0.6 |
Alcohol, g/day | 3.3 (6.7) | 3.6 (4.3) | 0.1 |
Smoking status | 0.03 | ||
Current smoker | 22.4 | 19.1 | |
Former smoker | 28.6 | 25.8 | |
Occasional smoker | 1.0 | 3.8 | |
Former occasional smoker | 9.2 | 7.2 | |
Non-smoker | 38.7 | 43.9 | |
Physical activityc | 0.1 | ||
Inactive | 18.7 | 17.9 | |
Moderately inactive | 35.4 | 35.9 | |
Moderately active | 28.2 | 27.3 | |
Active | 17.7 | 18.9 | |
Education | 0.04 | ||
Elementary school | 33.3 | 29.8 | |
Vocational (training) school | 28.1 | 26.2 | |
Secondary school | 22.3 | 20.6 | |
University education/college | 16.3 | 23.4 |
MetaMetabolite | Association with risk of developing type 2 diabetes at baseline | Changes in metabolites over time | Medication | ||||
---|---|---|---|---|---|---|---|
Directiona | Pathophysiologyb | Referencesc | ICC (95% CI)d | Cases vs controlse | Baseline vs follow-upf | ||
LysoPC(18:2) | – | HOMA-IR | 0.38 (0.26, 0.50) | Lower | |||
LysoPC(18:1) | – | HOMA-IR | 0.51 (0.40, 0.61) | Lower | |||
LysoPC(p-16:0) | – | HOMA-IR | 0.42 (0.31, 0.48) | Lower | Lower | ||
LysoPC(17:0) | – | HOMA-IR | 0.22 (0.11, 0.38) | Lower | Lower | ||
LysoPC(19:1) | – | HOMA-IR, HOMA-%B | 0.5 (0.40, 0.61) | Lower | Lower | ||
LysoPC(20:1) | – | HOMA-IR | [10] | 0.27 (0.17, 0.41) | Lower | ||
PC(16:0/16:1) | + | HOMA-IR | [48] | 0.25 (0.14, 0.40) | Higher | Affectedg | |
PC 583.3792@10.75 | – | HOMA-IR | 0.10 (0.03, 0.31) | Lower | |||
PC(16:1/14:0)h | + | 0.25 (0.14, 0.40) | Higher | ||||
PC(15:1/18:2)h | – | HOMA-IR, HOMA-%B | [10] | 0.45 (0.34, 0.56) | Lower | Lower | |
PC(17:0/18:2) | – | HOMA-IR | 0.21 (0.11, 0.38) | Lower | |||
DAG(16:1/16:1)h | + | HOMA-IR, HOMA-%B | 0.28 (0.16, 0.42) | Higher | Affectedg | ||
DAG(14:0/16:0)h | + | HOMA-IR, HOMA-%B | 0.31 (0.20, 0.45) | Higher | Affectedg | ||
DAG 531.4484@13.29h | + | HOMA-IR, HOMA-%B | 0.36 (0.25, 0.49) | Higher | Affectedg | ||
DAG 571.4437@13.30h | + | HOMA-IR, HOMA-%B | 0.40 (0.29, 0.53) | Higher | Affectedg | ||
DAG(14:0/18:1)h | + | HOMA-IR, HOMA-%B | 0.37 (0.25, 0.49) | Higher | Affectedg | ||
DAG(16:0/18:1)h | + | HOMA-IR, HOMA-%B | 0.43 (0.32, 0.55) | Higher | Affectedg | ||
Fatty acid 364.333@10.46 | + | HOMA-IRi | 0.35 (0.24, 0.48) | Higher | |||
Fatty acid 259.1608@7.63 | + | HOMA-IR, HOMA-%B | 0.49 (0.38, 0.59) | Higher | |||
2-Methylbutyroylcarnitine | + | HOMA-IRi | 0.54 (0.44, 0.64) | Higher | |||
3-Hydroxyisovalerylcarnitine | + | 0.41 (0.30, 0.53) | Higher | ||||
Phenylalanine | + | HOMA-IRi | 0.62 (0.53, 0.70) | Higher | Affectedg | ||
Leucine | + | HOMA-IR, HOMA-%B | 0.65 (0.57, 0.73) | Higher | Higher | ||
Isoleucine | + | HOMA-IR, HOMA-%B | 0.68 (0.59, 0.75) | Higher | Higher | ||
Valine | + | HOMA-IR, HOMA-%B | 0.50 (0.37, 0.58) | Higher | Higher | ||
Tryptophan | + | HOMA-IR, HOMA-B%i | [48] | 0.46 (0.35, 0.57) | Higher | Affectedg | |
l-Tyrosine | + | HOMA-IR | 0.50 (0.39, 0.60) | Higher | |||
Alanine | + | 0.32 (0.21, 0.45) | Higher | ||||
Citrulline | + | HOMA-IRi | [40] | 0.43 (0.32, 0.54) | – | ||
N-Acetylglycineh | – | HOMA-IR, HOMA-%Bi | [6] | 0.39 (0.28, 0.51) | Lower | Affectedg | |
2-Hydroxyethanesulfonate | – | HOMA-IR, HOMA-%Bi | 0.34 (0.23, 0.47) | Lower | Affectedg | ||
Glutamate | + | HOMA-IR, HOMA-%B | [49] | 0.39 (0.28, 0.52) | Higher | Higher | |
Glutamate derivate 316.0887@6.19 | + | HOMA-IR, HOMA-%B | 0.41 (0.30, 0.53) | Higher | Higher | ||
Bile acid386.2455 @8.21 | + | HOMA-IR, HOMA-%B | 0.65 (0.56, 0.72) | Higher | Higher | ||
3-Methyl-2-oxovaleric acid | + | HOMA-IRi | 0.61 (0.48, 0.67) | Higher | Higher | ||
161.0062@2.7 | – | HOMA-IR, HOMA-%B | 0.45 (0.35, 0.57) | Lower | Affectedg | ||
88.0162@1.71 | + | HOMA-IR | 0.23 (0.12, 0.38) | Higher | |||
198.0142 @1.71 | + | HOMA-IR | 0.24 (0.13, 0.40) | Higher | |||
491.1196@6.19 | – | HOMA-IR | 0.52 (0.42, 0.62) | Lower | |||
518.4333@12.07 | + | HOMA-IR, HOMA-%B | 0.40 (0.28, 0.52) | Higher | |||
590.4876@14.11 | + | HOMA-IR, HOMA-%B | 0.35 (0.24, 0.48) | Higher | |||
428.2242@7.98 | + | HOMA-IR, HOMA-%B | 0.76 (0.70, 0.82) | Higher | Affectedg | ||
566.3105@8.28 | + | HOMA-IR, HOMA-%B | 0.54 (0.44, 0.64) | Higher | |||
614.3679@8.60 | + | 0.63 (0.54, 0.71) | Higher | ||||
665.2645@9.87 | – | 0.50 (0.40, 0.61) | Lower | ||||
597.4023@10.93 | – | HOMA-IRi | 0.22 (0.12, 0.38) | Lower | Affectedg |