Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.
Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.
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BACKGROUND:Betaine is a major osmolyte, also important in methyl group metabolism.Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers.Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk? METHODS:Plasma samples were collected from 475 subjects four months after discharge following an acute coronary admission.
Death (n = 81), secondary acute MI (n = 87), admission for heart failure (n = 85), unstable angina (n = 72) and all cardiovascular events (n = 283) were recorded (median follow-up: 1804 days).RESULTS:High and low metabolite concentrations were defined as top or bottom quintile of the total cohort.In subjects with diabetes (n = 79), high plasma betaine was associated with increased frequencies of events; significantly for heart failure, hazard Antenna Adaptor ratio 3.
1 (1.2-8.2) and all cardiovascular events, HR 2.
8 (1.4-5.5).
In subjects without diabetes (n = 396), low plasma betaine was associated with events; significantly for secondary myocardial infarction, HR 2.1 (1.2-3.
6), unstable angina, HR 2.3 (1.3-4.
0), and all cardiovascular events, HR 1.4 (1.0-1.
9).In diabetes, high TMAO was a marker of all outcomes, HR 2.7 (1.
1-7.1) for death, 4.0 (1.
6-9.8) for myocardial infarction, 4.6 (2.
0-10.7) for heart failure, 9.1 (2.
8-29.7) for unstable angina and 2.0 (1.
1-3.6) for all cardiovascular events.In subjects without diabetes TMAO was only significant for death, HR 2.
7 (1.6-4.8) and heart failure, HR 1.
9 (1.1-3.4).
Adding the estimated glomerular filtration rate to Cox regression models tended to increase the apparent risks associated integrated Larder Fridge with low betaine.CONCLUSIONS:Elevated plasma betaine concentration is a marker of cardiovascular risk in diabetes; conversely low plasma betaine concentrations indicate increased risk in the absence of diabetes.We speculate that the difference reflects control of osmolyte retention in tissues.
Elevated plasma TMAO is a strong risk marker in diabetes.