Table 3.
Metabolites that were significantly associated with type 2 diabetes-risk in three distinct metabolomics profiles from two case-control samples, nested within the Nurses' Health Study.
| Case-control sample with repeated metabolomics profiles* |
Validation sample§ |
|||||
|---|---|---|---|---|---|---|
| First profile (1989-90) 10-year lag to T2D | Second profile (2000-01) No lag | Single profile (1989-90) No lag | ||||
| Metabolite | OR (95%CI) | FDR | OR (95%CI) | FDR | OR (95%CI) | FDR |
| leucine | 1.88 (1.50, 2.36) | 3E-06 | 2.80 (2.13, 3.68) | 1E-11 | 1.99 (1.60, 2.47) | 2E-08 |
| isoleucine | 2.05 (1.61, 2.61) | 8E-07 | 2.80 (2.13, 3.66) | 1E-11 | 2.12 (1.69, 2.66) | 3E-09 |
| valine | 1.60 (1.31, 1.94) | 9E-05 | 2.12 (1.70, 2.62) | 5E-10 | 2.18 (1.72, 2.74) | 3E-09 |
| alanine | 1.36 (1.13, 1.65) | 0.009 | 1.82 (1.51, 2.19) | 1E-08 | 1.79 (1.48, 2.18) | 9E-08 |
| glycine | 0.69 (0.57, 0.84) | 0.002 | 0.58 (0.48, 0.71) | 9E-07 | 0.63 (0.53, 0.73) | 2E-07 |
| C36:2 from DG/TG | 1.57 (1.26, 1.97) | 0.001 | 1.93 (1.52, 2.45) | 2E-06 | 1.60 (1.37, 1.88) | 1E-07 |
| C34:1 from DG/TG | 1.67 (1.35, 2.05) | 7E-05 | 2.08 (1.59, 2.7) | 2E-06 | 2.08 (1.71, 2.52) | 4E-11 |
| C34:2 from DG/TG | 1.70 (1.36, 2.12) | 1E-04 | 1.90 (1.48, 2.42) | 6E-06 | 1.82 (1.52, 2.18) | 3E-09 |
| C34:3 PC plasmalogen | 0.66 (0.55, 0.79) | 1E-04 | 0.59 (0.48, 0.72) | 9E-06 | 0.65 (0.55, 0.77) | 9E-06 |
| C38:5 from DG/TG | 1.52 (1.24, 1.87) | 9E-04 | 1.67 (1.35, 2.03) | 1E-05 | 1.63 (1.39, 1.93) | 1E-07 |
| C5 carnitine | 1.32 (1.11, 1.58) | 0.011 | 1.60 (1.32, 1.93) | 1E-05 | 1.40 (1.19, 1.67) | 4E-04 |
| C34:3 from DG/TG | 1.57 (1.25, 1.95) | 0.001 | 1.68 (1.37, 2.08) | 1E-05 | 1.60 (1.34, 1.89) | 1E-06 |
| C40:6 PE | 1.36 (1.13, 1.65) | 0.009 | 1.65 (1.35, 2.01) | 1E-05 | 1.54 (1.30, 1.80) | 3E-06 |
| homoarginine | 1.36 (1.13, 1.63) | 0.009 | 1.62 (1.32, 1.99) | 3E-05 | 1.40 (1.17, 1.70) | 0.002 |
| C34:1 from DG/TG | 1.55 (1.23, 1.95) | 0.002 | 1.62 (1.32, 1.98) | 3E-05 | 1.55 (1.33, 1.82) | 7E-07 |
| C36:3 from DG/TG | 1.65 (1.28, 2.11) | 0.001 | 1.63 (1.33, 2.02) | 4E-05 | 1.43 (1.24, 1.65) | 1E-05 |
| phenylalanine | 1.52 (1.25, 1.85) | 5E-04 | 1.43 (1.21, 1.70) | 2E-04 | 1.35 (1.14, 1.60) | 0.003 |
| C36:4 from DG/TG | 1.62 (1.29, 2.02) | 6E-04 | 1.51 (1.23, 1.83) | 3E-04 | 1.39 (1.20, 1.61) | 1E-04 |
| urate | 1.82 (1.49, 2.24) | 8E-07 | 1.38 (1.15, 1.65) | 0.002 | 1.48 (1.25, 1.73) | 2E-05 |
| C4 carnitine | 1.27 (1.08, 1.49) | 0.025 | 1.35 (1.14, 1.59) | 0.002 | 1.23 (1.05, 1.45) | 0.034 |
| C3 carnitine | 1.35 (1.14, 1.61) | 0.005 | 1.38 (1.15, 1.66) | 0.003 | 1.22 (1.05, 1.43) | 0.029 |
| tyrosine | 1.31 (1.08, 1.59) | 0.040 | 1.34 (1.12, 1.61) | 0.005 | 1.65 (1.35, 2.01) | 9E-06 |
| N4-acetylcytidine | 1.38 (1.14, 1.68) | 0.009 | 1.28 (1.07, 1.53) | 0.018 | 1.28 (1.11, 1.49) | 0.003 |
| DMGV | 1.36 (1.13, 1.63) | 0.009 | 1.23 (1.04, 1.46) | 0.035 | 1.45 (1.23, 1.70) | 9E-05 |
| beta-alanine | 1.34 (1.10, 1.60) | 0.018 | 1.26 (1.04, 1.53) | 0.047 | 1.39 (1.20, 1.62) | 1E-04 |
Type 2 diabetes case-control study with repeated metabolomics profiles: first metabolomics profile 1989/90 (n= 248 case-control pairs); second metabolomics profile in 2000/01 (n= 244 case-control pairs); type 2 diabetes incidence between 2002 and 2008.
Type 2 diabetes case-control study with one metabolomics profile in 1989/90 (n= 480 case-control pairs); type 2 diabetes incidence between 1992 and 2008.
OR (95%CI): odds ratio (95% confidence interval) per one standard deviation higher levels from a conditional logistic regression model, matched for age, race/ethnicity, time of blood draw, and adjusted for BMI [kg/m2], diet quality [AHEI-points], physical activity [METS-h/week], and smoking status [3 categories; never, current, past], assessed at the time of metabolomics profiling.
FDR: false discovery rate-controlled p-value (Wald test), adjusted for testing 170 metabolites.
Abbreviations - DG: diacylglycerol; DMGV: dimethylguanidino valerate; LPE: lysophosphatidylethanolamine; PC: phosphatidylcholine; PE: phosphatidylethanolamine, SM: sphingomyelin; T2D: type 2 diabetes; TG: triacylglycerol.