Table 3. Association of Serial Measurements of Plasma TMAO and Related Metabolites With Incident Type 2 Diabetes Among 4442 Participants in the Cardiovascular Health Study.
| Metabolite | Quintile, HR (95% CI)a | P value for trend | ||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | ||
| TMAO | ||||||
| Model 1 | 1 [Reference] | 1.11 (0.86-1.42) | 1.21 (0.95-1.54) | 0.95 (0.74-1.23) | 1.20 (0.94-1.55) | .46 |
| Model 2 | 1 [Reference] | 1.10 (0.86-1.42) | 1.21 (0.95-1.53) | 0.95 (0.73-1.23) | 1.19 (0.92-1.55) | .52 |
| Choline | ||||||
| Model 1 | 1 [Reference] | 1.08 (0.83-1.40) | 1.00 (0.77-1.30) | 0.95 (0.73-1.22) | 0.96 (0.74-1.24) | .45 |
| Model 2 | 1 [Reference] | 1.07 (0.83-1.39) | 0.99 (0.77-1.29) | 0.93 (0.72-1.21) | 0.94 (0.72-1.22) | .36 |
| Betaine | ||||||
| Model 1 | 1 [Reference] | 1.17 (0.93-1.48) | 1.03 (0.81-1.32) | 0.88 (0.68-1.14) | 0.88 (0.67-1.15) | .07 |
| Model 2 | 1 [Reference] | 1.17 (0.93-1.49) | 1.03 (0.80-1.31) | 0.88 (0.68-1.14) | 0.88 (0.67-1.15) | .07 |
| Carnitine | ||||||
| Model 1 | 1 [Reference] | 1.17 (0.92-1.50) | 1.08 (0.85-1.38) | 1.16 (0.91-1.48) | 1.07 (0.83-1.37) | .64 |
| Model 2 | 1 [Reference] | 1.17 (0.91-1.50) | 1.08 (0.85-1.38) | 1.16 (0.91-1.48) | 1.06 (0.82-1.37) | .68 |
| γ-Butyrobetaine | ||||||
| Model 1 | 1 [Reference] | 0.80 (0.63-1.01) | 0.72 (0.57-0.92) | 0.82 (0.64-1.05) | 0.79 (0.60-1.04) | .13 |
| Model 2 | 1 [Reference] | 0.79 (0.62-1.00) | 0.70 (0.55-0.90) | 0.79 (0.61-1.02) | 0.74 (0.55-1.00) | .07 |
| Crotonobetaine | ||||||
| Model 1 | 1 [Reference] | 1.04 (0.79-1.37) | 1.05 (0.85-1.30) | 1.12 (0.89-1.41) | 1.06 (0.83-1.35) | .45 |
| Model 2 | 1 [Reference] | 1.04 (0.79-1.37) | 1.05 (0.85-1.30) | 1.11 (0.88-1.40) | 1.05 (0.82-1.35) | .50 |
Abbreviations: HR, hazard ratio; TMAO, trimethylamine N-oxide.
a
Hazard ratios for incident type 2 diabetes comparing each of the 4 higher metabolite quintiles with the lowest (reference) quintile, obtained from Cox proportional hazards regression models with serial measures of metabolite and time-updated covariates. Model 1 adjusted for age, sex, race, site, educational attainment, income, body mass index, waist circumference, smoking, physical activity, systolic blood pressure, hypertension, low-density lipoprotein cholesterol, coronary heart disease, animal-sourced food consumption, and total energy intake. Model 2 additionally adjusted for estimated glomerular filtration rate.