Abstract

Trimethylamine N-oxide (TMAO) is associated with type 2 diabetes (T2DM) and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18) were randomized to consume a standardized diet (55% carbohydrate, 30% fat) with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine) before and after the diet. Plasma TMAO and trimethylamine (TMA) moieties (choline, l-carnitine, betaine, and γ-butyrobetaine) were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05). There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.

Highlights

  • Recent estimates indicate that the prevalence of prediabetes is increasing worldwide and the number people suffering from type 2 diabetes (T2DM) will likely exceed 470 million by 2030 [1].Importantly, prediabetes is associated with a high risk for both development of T2DM as well as adverse cardiovascular disease (CVD)-related events [2,3]

  • Prediabetes is associated with a high risk for both development of T2DM as well as adverse cardiovascular disease (CVD)-related events [2,3]

  • Trimethylamine N-oxide (TMAO), a metabolite originating from gut microbial metabolism of dietary

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Summary

Introduction

Recent estimates indicate that the prevalence of prediabetes is increasing worldwide and the number people suffering from type 2 diabetes (T2DM) will likely exceed 470 million by 2030 [1]. Prediabetes is associated with a high risk for both development of T2DM as well as adverse cardiovascular disease (CVD)-related events [2,3]. Trimethylamine N-oxide (TMAO), a metabolite originating from gut microbial metabolism of dietary. Nutrients 2018, 10, 793 trimethylamine (TMA)-containing moieties, has been reported to be elevated in T2DM and predictive of future cardiovascular events in several independent cohorts [4,5,6,7,8]. There are presently no efficacious interventions for reducing plasma TMAO concentrations in humans. The available evidence does not support the use of probiotics to reduce plasma TMAO concentrations [12,13]. We tested the hypothesis that inulin, a prebiotic fiber from chicory root, would reduce plasma TMAO concentrations in middle-aged and older adults at risk for T2DM

Participants
Experimental Design
Controlled Feeding
Procedures
Fasting and Postprandial Blood Collection
Mass Spectrometry
Statistical Analyses
Participant Characteristics
Dietary Intake
Thereinin were
Fasting and Postprandial Plasma TMAO and TMA Moiety Concentrations
Correlations
Discussion
Conclusions
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