Abstract
Purpose
Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes?
Methods
Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants.
Results
Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy.
Conclusions
Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.
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Acknowledgments
The DEWL trial was funded by the Health Research Council of New Zealand (06/337). Other work has been made possible with support from the Heart Foundation of New Zealand, the Maurice & Phyllis Paykel Trust, and equipment funded by Lotteries Health NZ. None of the sponsors had any role in the conduct of the research or its interpretation.
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Lever, M., McEntyre, C.J., George, P.M. et al. Extreme Urinary Betaine Losses in Type 2 Diabetes Combined with Bezafibrate Treatment are Associated with Losses of Dimethylglycine and Choline but not with Increased Losses of Other Osmolytes. Cardiovasc Drugs Ther 28, 459–468 (2014). https://doi.org/10.1007/s10557-014-6542-9
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DOI: https://doi.org/10.1007/s10557-014-6542-9