Abstract
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.
Highlights
The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) is a longitudinal cohort study investigating the relationship between subgingival microbial community composition, systemic inflammatory phenotype and impaired glucose metabolism[13]
We report that TMAO levels were not associated with insulin resistance, HbA1c or fasting plasma glucose cross-sectionally, or with longitudinal change in fasting plasma glucose
TMAO levels were associated with a modest increase in the prevalence of prediabetes in a nonlinear fashion such that participants with intermediate TMAO levels had a statistically significant 94% increase in prediabetes prevalence
Summary
Type 2 diabetes is an important public health problem with over 400 million diagnosed cases globally, and in the United States the prevalence of diagnosed diabetes increased from 0.93%. Only one longitudinal study has explored baseline TMAO as a predictor of future diabetes development [12] and, surprisingly, they report elevated TMAO levels to be related to decreased type 2 diabetes risk. No existing studies have explored the relationship between TMAO and early risk biomarkers linked to future type 2 diabetes development such as insulin resistance, rising longitudinal glucose levels or prediabetes. We hypothesize that elevated plasma TMAO-levels would be associated with markers of insulin resistance and impaired glucose regulation, cross-sectionally, as well as with rising glucose levels, longitudinally. These investigations are undertaken in a diabetesfree population without a history of cardiovascular and/or kidney disease
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