Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

Abstract

Background: Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, onecarbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Methods: Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Results: Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality ¼ 0.52) and urine (index of individuality ¼ 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and À35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to À80% in plasma). Conclusions: Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value.

Microbiome, trimethylamine N-oxide, and cardiometabolic disease

“…48, 49 Current data supports the conclusion that the major origin of inter-individual differences is due to the large diversity of gut microbiota and community structure among individuals. Recent observations indicate that overall gut microbial community structure is modulated by long-term dietary exposure.…”

TMAO: A small molecule of great expectations

“…On the other hand, it has been found that diabetic patients treated with metformin showed decreased glucose but increased plasma TMAO compared to untreated ones [72]. Other studies suggest a low diagnostic value of TMAO measurements in obese diabetic patients due to high variability of plasma TMAO concentrations [73]. To our knowledge, the level of plasma TMAO in diabetic laboratory animals has not yet been reported.…”

Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance

“…While the association between TMAO and atherosclerosis initially reported by Tang et al. (2013) is now accepted (Bennett et al., 2013, Koeth et al., 2013, Koeth et al., 2014, Ussher et al., 2013, Wang et al., 2011b), the roles played by TMAO in glucose homeostasis are less clear (Bai et al., 1998, Gao et al., 2014, Lever et al., 2014, McEntyre et al., 2015). …”