TABLE 2.
Incident type 2 diabetes by baseline glycolysis/gluconeogenesis and TCA cycle fasting plasma metabolites in the PREDIMED trial, 2003–20101
| Type 2 diabetes cases | Adjusted HR per 1-SD increment2 (95% CI) | Adjusted HR (95% CI) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| n | Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | P-trend | P-trend3 | |||
| Hexose monophosphate4 | 889 | 251 | 1.23 (1.07, 1.41) | 1.00 (ref) | 2.45 (1.62, 3.69) | 1.12 (0.73, 1.71) | 2.37 (1.58, 3.54) | 0.214 | 0.333 |
| Hexose diphosphate4 | 570 | 166 | 1.12 (0.93, 1.33) | 1.00 (ref) | 0.65 (0.41, 1.03) | 1.74 (1.20, 2.54) | 0.89 (0.57, 1.41) | 0.530 | 0.619 |
| 3-Phosphoglycerate | 887 | 251 | 1.13 (0.97, 1.32) | 1.00 (ref) | 1.24 (0.85, 1.82) | 1.28 (0.84, 1.94) | 1.27 (0.84, 1.92) | 0.475 | 0.619 |
| Phosphoenolpyruvate | 885 | 250 | 1.13 (0.96, 1.32) | 1.00 (ref) | 0.87 (0.58, 1.30) | 0.77 (0.51, 1.16) | 1.40 (0.94, 2.10) | 0.045 | 0.104 |
| Pyruvate | 780 | 238 | 1.31 (1.11, 1.54) | 1.00 (ref) | 1.84 (1.21, 2.82) | 1.36 (0.88, 2.09) | 2.12 (1.37, 3.28) | 0.034 | 0.096 |
| Lactate | 889 | 251 | 1.26 (1.07, 1.48) | 1.00 (ref) | 0.92 (0.58, 1.44) | 1.70 (1.11, 2.61) | 1.66 (1.06, 2.59) | <0.001 | <0.001 |
| Alanine | 889 | 251 | 1.25 (1.08, 1.45) | 1.00 (ref) | 0.58 (0.37, 0.92) | 1.16 (0.78, 1.72) | 1.23 (0.83, 1.83) | <0.001 | 0.001 |
| Glycerol 3-phosphate | 889 | 251 | 1.44 (1.24, 1.67) | 1.00 (ref) | 1.18 (0.80, 1.74) | 1.29 (0.84, 1.96) | 2.74 (1.83, 4.09) | 0.002 | 0.007 |
| Citrate | 889 | 251 | 1.00 (0.86, 1.17) | 1.00 (ref) | 0.89 (0.62, 1.27) | 0.81 (0.54, 1.22) | 0.93 (0.62, 1.40) | 0.866 | 0.866 |
| Aconitate | 889 | 251 | 1.14 (0.98, 1.33) | 1.00 (ref) | 1.08 (0.70, 1.68) | 1.11 (0.75, 1.65) | 1.48 (0.98, 2.23) | 0.069 | 0.138 |
| Isocitrate | 889 | 251 | 1.17 (1.01, 1.36) | 1.00 (ref) | 1.36 (0.89, 2.08) | 0.95 (0.60, 1.50) | 1.58 (1.04, 2.40) | 0.023 | 0.080 |
| Fumarate/maleate4 | 889 | 251 | 1.02 (0.88, 1.18) | 1.00 (ref) | 0.67 (0.43, 1.03) | 0.75 (0.51, 1.10) | 0.96 (0.64, 1.45) | 0.204 | 0.333 |
| Malate | 889 | 251 | 1.04 (0.91, 1.19) | 1.00 (ref) | 0.94 (0.64, 1.39) | 1.23 (0.82, 1.85) | 1.14 (0.79, 1.65) | 0.778 | 0.837 |
| Succinate | 889 | 251 | 1.07 (0.93, 1.25) | 1.00 (ref) | 1.48 (1.03, 2.13) | 1.38 (0.96, 2.00) | 0.94 (0.60, 1.49) | 0.516 | 0.619 |
| Metabolite score5 | 889 | 251 | 1.30 (1.12, 1.51) | 1.00 (ref) | 1.11 (0.70, 1.75) | 1.32 (0.86, 2.01) | 1.88 (1.25, 2.83) | 0.001 | |
Models adjusted for age (years), sex (male, female), intervention group (MedDiet + extra-virgin olive oil, MedDiet + nuts), BMI (kg/m2), smoking (never, current, former), leisure-time physical activity (metabolic equivalent tasks in minutes per day), dyslipidemia, hypertension, and baseline fasting glucose (mean + quadratic term of centered mean) and stratified by recruitment center. TCA, tricarboxylic acid cycle.
An inverse normal transformation was applied to raw values.
False discovery rate–corrected P value.
These metabolites were not chromatographically resolved and do not have unique multiple reaction monitoring transitions in MS.
Weighted sum of all metabolites (using regression coefficients as weights after applying the leave-one-out cross-validation approach). Weighted proportional hazards Cox regression models were used.