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PLoS One. 2014 Dec 10;9(12):e114969. doi: 10.1371/journal.pone.0114969. eCollection 2014.

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.

Author information

1
Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand; Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
2
Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
3
The Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
4
Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand.

Abstract

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 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 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.

PMID:
25493436
PMCID:
PMC4262445
DOI:
10.1371/journal.pone.0114969
[Indexed for MEDLINE]
Free PMC Article

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