Trimethylamine-N-oxide (TMAO)–a gut-microbiota metabolite–is a biomarker of cardiometabolic risk. No studies have investigated TMAO as an early biomarker of longitudinal glucose increase or prevalent impaired glucose regulation. In a longitudinal cohort study, 300 diabetes-free men and women (77%) aged 20–55 years (mean = 34±10) were enrolled at baseline and re-examined at 2-years to investigate the association between TMAO and biomarkers of diabetes risk. Plasma TMAO was measured using Ultra Performance Liquid Chromatography-Mass Spectrometry. After an overnight fast, FPG was measured longitudinally, HbA1C and insulin were measured only at baseline. Insulin resistance was defined using HOMA-IR. Multivariable generalized linear models regressed; i) FPG change (year 2 minus baseline) on baseline TMAO tertiles; and ii) HOMA-IR and HbA1c on TMAO tertiles. Multivariable relative risk regressions modeled prevalent prediabetes across TMAO tertiles. Mean values of 2-year longitudinal FPG±SE across tertiles of TMAO were 86.6±0.9, 86.7 ±0.9, 86.4±0.9 (p = 0.98). Trends were null for FPG, HbA1c, HOMA-IR, cross-sectionally. The prevalence ratio of prediabetes among participants in 2nd and 3rd TMAO tertiles (vs. the 1st) were 1.94 [95%CI 1.09–3.48] and 1.41 [95%CI: 0.76–2.61]. TMAO levels are associated with increased prevalence of prediabetes in a nonlinear fashion but not with insulin resistance or longitudinal FPG change.
Bibliographical noteFunding Information:
This research was supported by NIH grants R00 DE018739, R21 DE022422 and R01 DK 102932 to Dr. Demmer. This publication was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the following individuals for their invaluable contributions to this research: the 1199 SEIU, HS-3/SSA Area leadership including Ms. Consuelo Mclaughin, Mr. Bennett Batista, Mr. Victor Rivera; Ms. Romanita Celenti for her efforts in performing phlebotomy and processing and analyzing plaque samples; Ms. Aleksandra Zuk and Garazi Zulaika for their leadership and excellent program coordination; Drs. Nidhi Arora, Ashwata Pokherel, Publio Silfa & Thomas Spinell for their skilled examinations and essential participant engagement. We are also profoundly grateful to the ORIGINS participants, for their participation in this research.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural