Table 2.
Associations of 10-year-plasma metabolite changes (2000/01 vs. 1989/90) with subsequent risk of developing type 2 diabetes (2002-2008).
| Categorical analysis |
Continuous analysis |
|||||||
|---|---|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | P- | |||
| Metabolite | OR (95%CI) | OR (95%CI) | OR (95%CI) | OR (95%CI) | Trend | OR (95%CI) | FDR | |
| Δisoleucine | ref. | 1.68 (1.12, 2.56) | 1.95 (1.26, 3.01) | 2.23 (1.44, 3.48) | 3.53 (2.23, 5.54) | 2E-07 | 2.72 (1.97, 3.79) | 3E-07 |
| Δleucine | ref. | 1.27 (0.84, 1.93) | 1.40 (0.92, 2.14) | 1.82 (1.15, 2.89) | 2.56 (1.70, 3.89) | 4E-06 | 2.53 (1.86, 3.47) | 4E-07 |
| Δvaline | ref. | 1.35 (0.84, 2.16) | 1.72 (1.10, 2.70) | 1.70 (1.05, 2.76) | 2.61 (1.64, 4.17) | 5E-05 | 1.93 (1.52, 2.44) | 3E-06 |
| Δretinol | ref. | 1.36 (0.88, 2.11) | 1.31 (0.83, 2.05) | 1.75 (1.12, 2.74) | 2.23 (1.40, 3.54) | 8E-04 | 1.82 (1.44, 2.30) | 3E-05 |
| ΔN-acetylaspartic acid | ref. | 0.92 (0.64, 1.34) | 0.70 (0.45, 1.11) | 0.56 (0.36, 0.88) | 0.55 (0.35, 0.88) | 0.002 | 0.54 (0.42, 0.70) | 1E-04 |
| ΔC4-OH carnitine | ref. | 1.38 (0.86, 2.23) | 1.75 (1.08, 2.87) | 2.27 (1.41, 3.64) | 2.53 (1.57, 4.10) | 2E-05 | 1.84 (1.41, 2.40) | 2E-04 |
| Δalanine | ref. | 1.67 (1.13, 2.44) | 1.39 (0.93, 2.07) | 1.62 (1.03, 2.53) | 2.18 (1.37, 3.48) | 0.011 | 1.68 (1.31, 2.16) | 9E-04 |
| ΔC20:0 LPE | ref. | 1.00 (0.70, 1.44) | 0.85 (0.57, 1.28) | 0.54 (0.35, 0.84) | 0.63 (0.41, 0.96) | 0.003 | 0.68 (0.56, 0.82) | 0.001 |
| Δglycocholate | ref. | 1.43 (0.93, 2.19) | 1.48 (0.97, 2.25) | 1.67 (1.10, 2.55) | 1.67 (1.01, 2.73) | 0.016 | 1.58 (1.26, 2.00) | 0.001 |
| ΔC16:1 SM | ref. | 0.72 (0.49, 1.06) | 0.67 (0.45, 1.00) | 0.97 (0.66, 1.44) | 0.39 (0.24, 0.64) | 0.004 | 0.68 (0.56, 0.83) | 0.002 |
| ΔC5 carnitine | ref. | 1.21 (0.78, 1.87) | 1.13 (0.70, 1.82) | 1.95 (1.25, 3.05) | 2.14 (1.37, 3.33) | 1E-04 | 1.57 (1.24, 1.99) | 0.002 |
| Δmethionine | ref. | 1.11 (0.72, 1.71) | 1.13 (0.75, 1.70) | 1.14 (0.71, 1.80) | 1.92 (1.24, 2.96) | 0.015 | 1.55 (1.24, 1.95) | 0.002 |
| ΔC36:2 from DG/TG | ref. | 1.48 (0.97, 2.23) | 1.20 (0.78, 1.83) | 1.28 (0.84, 1.97) | 1.82 (1.16, 2.87) | 0.049 | 1.62 (1.25, 2.07) | 0.003 |
| ΔC16:0 SM | ref. | 0.85 (0.59, 1.25) | 0.73 (0.50, 1.06) | 0.70 (0.47, 1.06) | 0.64 (0.42, 1.00) | 0.025 | 0.66 (0.52, 0.82) | 0.003 |
| ΔC34:1 from DG/TG | ref. | 1.34 (0.86, 2.09) | 1.86 (1.22, 2.85) | 1.65 (1.06, 2.57) | 1.99 (1.23, 3.21) | 0.002 | 1.68 (1.26, 2.24) | 0.005 |
| Δpantothenate | ref. | 1.38 (0.87, 2.16) | 1.58 (1.02, 2.48) | 1.34 (0.80, 2.21) | 1.80 (1.09, 2.99) | 0.008 | 1.55 (1.21, 1.97) | 0.005 |
| ΔC38:6 PE | ref. | 1.11 (0.70, 1.75) | 1.12 (0.72, 1.73) | 1.68 (1.10, 2.60) | 1.42 (0.90, 2.26) | 0.019 | 1.43 (1.17, 1.76) | 0.005 |
| ΔC36:4 PE | ref. | 1.31 (0.84, 2.03) | 1.36 (0.88, 2.11) | 1.52 (0.97, 2.36) | 1.72 (1.09, 2.70) | 0.015 | 1.45 (1.17, 1.78) | 0.005 |
| ΔC40:6 PE | ref. | 1.14 (0.73, 1.77) | 1.26 (0.84, 1.87) | 1.35 (0.89, 2.05) | 1.82 (1.19, 2.78) | 0.007 | 1.48 (1.19, 1.86) | 0.005 |
| ΔC36:3 PE plasmalogen | ref. | 0.76 (0.52, 1.11) | 0.72 (0.48, 1.07) | 0.58 (0.38, 0.89) | 0.68 (0.46, 1.01) | 0.017 | 0.74 (0.62, 0.88) | 0.006 |
| ΔC16:1 LPC plasmalogen | ref. | 0.83 (0.55, 1.24) | 0.78 (0.52, 1.18) | 0.64 (0.40, 1.0) | 0.64 (0.42, 0.99) | 0.028 | 0.68 (0.54, 0.85) | 0.007 |
| ΔC36:2 PE | ref. | 1.43 (0.95, 2.16) | 1.22 (0.79, 1.86) | 1.35 (0.87, 2.10) | 2.32 (1.45, 3.72) | 0.011 | 1.42 (1.15, 1.76) | 0.008 |
| ΔC34:3 PC plasmalogen | ref. | 0.70 (0.47, 1.03) | 0.59 (0.39, 0.88) | 0.58 (0.38, 0.88) | 0.63 (0.42, 0.93) | 0.019 | 0.70 (0.55, 0.89) | 0.020 |
| ΔC34:2 PE | ref. | 1.67 (1.06, 2.58) | 1.31 (0.83, 2.06) | 1.57 (1.01, 2.43) | 2.05 (1.28, 3.32) | 0.012 | 1.38 (1.11, 1.70) | 0.020 |
| ΔC34:2 from DG/TG | ref. | 1.20 (0.76, 1.86) | 1.48 (0.96, 2.24) | 1.43 (0.93, 2.21) | 1.73 (1.10, 2.77) | 0.011 | 1.46 (1.13, 1.89) | 0.022 |
| Δglutamine | ref. | 0.80 (0.55, 1.17) | 0.67 (0.44, 1.01) | 0.50 (0.32, 0.77) | 0.69 (0.45, 1.07) | 0.015 | 0.74 (0.61, 0.91) | 0.027 |
| ΔC38:4 PE | ref. | 1.12 (0.71, 1.73) | 1.43 (0.94, 2.19) | 1.17 (0.76, 1.82) | 1.80 (1.15, 2.84) | 0.021 | 1.31 (1.09, 1.59) | 0.027 |
| ΔC18:2 SM | ref. | 0.81 (0.56, 1.18) | 0.70 (0.48, 1.05) | 0.64 (0.43, 0.94) | 0.64 (0.41, 0.99) | 0.006 | 0.78 (0.65, 0.93) | 0.028 |
| Δglycine | ref. | 0.84 (0.58, 1.21) | 0.55 (0.37, 0.83) | 0.64 (0.43, 0.95) | 0.52 (0.34, 0.79) | 6E-04 | 0.73 (0.58, 0.91) | 0.030 |
| ΔC14:0 SM | ref. | 0.90 (0.61, 1.32) | 0.83 (0.56, 1.24) | 0.93 (0.62, 1.41) | 0.58 (0.36, 0.92) | 0.045 | 0.77 (0.64, 0.93) | 0.030 |
| ΔGDX / GCDC | ref. | 1.72 (1.10, 2.65) | 1.72 (1.10, 2.67) | 1.42 (0.88, 2.28) | 1.97 (1.19, 3.28) | 0.044 | 1.35 (1.08, 1.67) | 0.033 |
Shown are 10-year metabolite changes with nominally significant trend test in the categorical analysis (P < 0.05) and a significant multiple testing-corrected T2D risk association in the continuous analysis (FDR < 0.05, Wald test). Case-control sample with repeated metabolomics profiles (1989/90 and 2000/01) and subsequent type 2 diabetes incidence (between 2002 and 2008), n= 244 cases and n = 244 controls, 1:1 matched for age, race/ethnicity, and time of blood draw.
OR (95%CI): odds ratio (95% confidence interval) per one standard deviation higher levels from a conditional logistic regression model, adjusted for baseline metabolite level, BMI [kg/m2], diet quality [AHEI-points], physical activity [METS-h/week], ΔBMI (2000 vs. 1990), ΔAHEI (1998 vs. 1990), ΔMETS (2000 vs. 1988), and smoking status [3 categories; never, current, past] at both blood sampling time points.
Q1-Q5: The case-control sample was categorised according to the quintiles of the metabolite distribution; for the categorical analysis, models were not conditioned on matched case-control pair but adjusted for age, all other adjustments remaining the same.
FDR: false discovery rate-controlled p-value (Wald test), adjusted for testing 170 known metabolites.
Δ: 10-year changes (1989/90 vs. 2000/01).
Abbreviations - DG: diacylglycerol, TG: triacylglycerol, PE: phosphatidylethanolamine, LPE: lysophosphatidylethanolamine, PC: phosphatidylcholine, LPC: lysophosphatidylcholine, SM: sphingomyelin, GDX: glycodeoxycholate, GCDC: glycochenodeoxycholate.