Table 2.
Associations between urinary metabolite levels and prevalent T2D in the discovery and replication samples in logistic regression adjusted for age, sex (for PIVUS only) and urinary creatinine per standard deviation unit increase in metabolite level.
| Discovery (PIVUS, n = 789) | Replication (ULSAM, n = 635) | ||||
|---|---|---|---|---|---|
| Metabolite (preliminary annotation with RamClust) | OR (95% CI) | P value | OR (95% CI) | P value | |
| 3-Methylxanthine | 0.70 (0.59–0.84) | 7.93 × 10−5 | 3-Methylxanthine | 0.84 (0.68–1.05) | 0.125 |
| 2-Hepteneoylglycine | 0.70 (0.58–0.84) | 1.31 × 10−4 | 2-Hepteneoylglycine | 1.06 (0.82–1.36) | 0.681 |
| Nonanoylcarnitine | 0.71 (0.57–0.88) | 1.44 × 10−3 | Nonanoylcarnitine | 0.71 (0.56–0.89) | 3.11 × 10−3 |
| L-Tyrosine | 1.36 (1.12–1.66) | 2.05 × 10−3 | L-Tyrosine | 1.04 (0.81–1.32) | 0.769 |
| NPC (irinotecan metabolite) | 0.76 (0.63–0.91) | 3.53 × 10−3 | NPC (irinocetan metabolite) | 0.85 (0.68–1.06) | 0.154 |
| 3-hydroxyundecanoyl-carnitine | 0.78 (0.65–0.93) | 4.71 × 10−3 | 3-hydroxyundecanoyl-carnitine (C-580) | 0.61 (0.47–0.79) | 1.56 × 10−4 |
| Vildagliptin | 0.79 (0.67–0.93) | 5.47 × 10−3 | Vildagliptin | 0.93 (0.73–1.19) | 0.572 |
| Methysergide | 0.77 (0.64–0.94) | 9.49 × 10−3 | – | – | – |
| Pilocarpine | 0.78 (0.65–0.95) | 0.012 | – | – | – |
| 2-Methoxyestradiol | 0.79 (0.66–0.95) | 0.012 | – | – | – |
| Phthalic anhydride | 1.26 (1.04–1.53) | 0.016 | – | – | – |
| (3a,5b,7a,12a)-24-[(carboxymethyl)amino]-1,12-dihydroxy-24-oxocholan-3-yl-b-D-Glucopyranosiduronic acid | 1.24 (1.01–1.52) | 0.044 | – | – | – |
| Methylcysteine | 0.85 (0.72–1.00) | 0.047 | – | – | – |
| L-Urobilin | 1.22 (1.00–1.50) | 0.053 | – | – | – |
| Dihyroxy-1H-Indole-glucuronide | 1.24 (0.99–1.55) | 0.06 | – | – | – |
| Sotalol | 0.79 (0.62–1.02) | 0.067 | – | – | – |
| N-Stearoyl-phenylalanine | 1.20 (0.98–1.46) | 0.073 | – | – | – |
| Glutarylcarnitine | 0.85 (0.70–1.02) | 0.078 | – | – | – |
| 3-hydroxydecanoyl-carnitine (C-580) | 0.85 (0.71–1.02) | 0.087 | – | – | – |
| 2-Octenoylcarnitine | 0.87 (0.73–1.02) | 0.089 | – | – | – |
| Dynorphin-A | 1.21 (0.97–1.50) | 0.089 | – | – | – |
| trans-Ferulic acid | 1.19 (0.97–1.45) | 0.091 | – | – | – |
| 3-hydroxy-2-methyl-2-sulfooxy-methyl-propanoic acid | 0.84 (0.68–1.03) | 0.091 | – | – | – |
| C4H8O2S4 | 0.85 (0.71–1.03) | 0.093 | – | – | – |
| Glutaconylcarnitine | 1.20 (0.96–1.50) | 0.102 | – | – | – |
| Proline-betaine | 0.85 (0.70–1.04) | 0.117 | – | – | – |
| Codeine-6-glucuronide | 0.80 (0.60–1.06) | 0.119 | – | – | – |
| C5H14S | 1.18 (0.96–1.47) | 0.123 | – | – | – |
| 4-Hepteneoylglycine | 0.85 (0.69–1.05) | 0.124 | – | – | – |
| Hydralazine-pyruvate-hydrazone | 0.88 (0.72–1.07) | 0.193 | – | – | – |
| Estrone | 0.89 (0.75–1.06) | 0.194 | – | – | – |
| L-Proline | 1.14 (0.93–1.40) | 0.2 | – | – | – |
| Cortexolone | 0.89 (0.74–1.07) | 0.207 | – | – | – |
| Prednicarbate | 1.14 (0.92–1.41) | 0.238 | – | – | – |
| Pantothenic acid | 1.13 (0.92–1.38) | 0.245 | – | – | – |
| 5-3-4-Dihydroxyphenyl-gamma-valerolactone-3-O-methyl-4-O-glucuronide | 0.91 (0.74–1.11) | 0.352 | – | – | – |
| Androstenedione | 0.92 (0.76–1.12) | 0.399 | – | – | – |
| gamma-Glutamylphenylalanine | 1.09 (0.89–1.34) | 0.407 | – | – | – |
| Chenodeoxycholic acid-glycine conjugate | 1.09 (0.88–1.34) | 0.43 | – | – | – |
| N-acetyltryptophan | 1.08 (0.88–1.34) | 0.45 | – | – | – |
| C4NO3P | 0.92 (0.74–1.14) | 0.454 | – | – | – |
| 2-Hexenoylcarnitine | 0.93 (0.76–1.14) | 0.495 | – | – | – |
| Glucosamine | 1.07 (0.87–1.33) | 0.51 | – | – | – |
| gamma-Glutamylvaline | 1.06 (0.86–1.31) | 0.563 | – | – | – |
| Pyroglutamic acid | 0.95 (0.79–1.14) | 0.581 | – | – | – |
| Dihydroferulic acid-4-O-glucuronide | 1.06 (0.87–1.29) | 0.584 | – | – | – |
| Nabilone | 1.05 (0.86–1.29) | 0.619 | – | – | – |
| Acetaminophen glucuronide | 0.96 (0.79–1.17) | 0.662 | – | – | – |
| Ajmaline | 1.04 (0.85–1.28) | 0.671 | – | – | – |
| 7-hydroxygranisetron | 1.04 (0.84–1.29) | 0.699 | – | – | – |
| Indoleacrylic acid | 1.0 4 (0.85–1.28) | 0.714 | – | – | – |
| Paramethadione | 0.97 (0.79–1.18) | 0.747 | – | – | – |
| 5-Hydroxy-6-methoxyindole-glucuronide | 1.03 (0.84–1.26) | 0.757 | – | – | – |
| Tyrosinamide | 0.97 (0.79–1.19) | 0.772 | – | – | – |
| Zolmitriptan | 0.98 (0.80–1.20) | 0.855 | – | – | – |
| 6b-hydroxybudesonide | 1.01 (0.82–1.25) | 0.893 | – | – | – |
| Atenolol acid | 0.99 (0.81–1.22) | 0.919 | – | – | – |
| Tranexamic acid | 0.99 (0.81–1.21) | 0.936 | – | – | – |
| L-Glutamine | 0.99 (0.81–1.22) | 0.945 | – | – | – |
| Hesperetin | 1.00 (0.82–1.23) | 0.985 | – | – | – |
| L-Octanoylcarnitine | 1.00 (0.81–1.24) | 0.999 | – | – | – |
| 11-Hydroxyprogesterone-11-glucuronide | 1.00 (0.81–1.24) | 0.999 | – | – | – |
Metabolites associated at a false discovery rate of 5% in the discovery sample PIVUS were tested in ULSAM. The names reflect the initial, automated data-driven annotation as explained in the Methods section. The shown P values are unadjusted.