Dataset Information

Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes.

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.

SUBMITTER: Baugh ME

PROVIDER: S-EPMC6024751 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes.

Baugh Mary Elizabeth ME Steele Cortney N CN Angiletta Christopher J CJ Mitchell Cassie M CM Neilson Andrew P AP Davy Brenda M BM Hulver Matthew W MW Davy Kevin P KP

Nutrients 20180620 6

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 ...[more]

PMID: 29925775

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Project description:BackgroundThe microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear.ObjectiveThe aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study.DesignA 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24-32 wk of gestation). An independent-phase study, with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography-tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test.ResultsIn the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47).ConclusionsConsistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. This trial was registered at www.clinicaltrials.gov as NCT03415295.

Project description:ImportanceAlthough rodent studies suggest that trimethylamine N-oxide (TMAO) influences glucose homeostasis and risk of type 2 diabetes, evidence in humans is limited.ObjectiveTo examine the associations of serial measures of plasma TMAO and related metabolite concentrations with incident type 2 diabetes, fasting plasma insulin and glucose levels, and the Gutt insulin sensitivity index (ISI).Design, setting, and participantsThis prospective cohort design assessed the association of plasma TMAO and related metabolite concentrations with diabetes outcome, whereas a cross-sectional design assessed the association with insulin and glucose levels and Gutt ISI. The participants were a cohort of older US adults from the Cardiovascular Health Study (CHS). Data from June 1989 to May 1990, from November 1992 to June 1993, and from June 1995 to June 1997 were included, with follow-up through June 2010. Levels of TMAO and related metabolites were measured in CHS plasma samples. Data were analyzed from July 2019 to September 2020.ExposuresPlasma concentrations of TMAO, carnitine, betaine, choline, crotonobetaine, and γ-butyrobetaine, measured by high-performance liquid chromatography and mass spectrometry.Main outcomes and measuresLinear regression for associations of TMAO and related metabolites with insulin and glucose levels and Gutt ISI, and proportional hazards regression for associations with diabetes.ResultsThe study included 4442 participants without diabetes at baseline (mean [SD] age, 73 [6] years at entry; 2710 [61%] women). In multivariable analyses, plasma TMAO, carnitine, crotonobetaine, and γ-butyrobetaine concentrations were positively associated with fasting insulin level (insulin mean geometric ratio comparing fifth with first quintiles of metabolite concentration: 1.07 [95% CI, 1.04-1.10] for TMAO; 1.07 [95% CI, 1.03-1.10] for carnitine; 1.05 [95% CI, 1.02-1.08] for crotonobetaine; and 1.06 [95% CI, 1.02-1.09] for γ-butyrobetaine). In contrast, betaine and choline concentrations were associated with greater insulin sensitivity (mean difference in Gutt ISI comparing fifth with first quintiles: 6.46 [95% CI, 4.32-8.60] and 2.27 [95% CI, 0.16-4.38], respectively). Incident diabetes was identified in 661 participants during a median 12.1 (interquartile range, 6.9-17.1) years of follow-up. In multivariable analyses, TMAO and metabolites were not significantly associated with type 2 diabetes risk (hazard ratios of diabetes comparing fifth with first quintile: 1.20 [95% CI, 0.94-1.55] for TMAO; 0.96 [95% CI, 0.74-1.24] for choline; 0.88 [95% CI, 0.67-1.15] for betaine; 1.07 [95% CI, 0.83-1.37] for carnitine; 0.79 [95% CI, 0.60-1.04] for γ-butyrobetaine; and 1.06 [95% CI, 0.83-1.35] for crotonobetaine).Conclusions and relevancePlasma TMAO and related metabolites were not significantly associated with type 2 diabetes among older adults. The metabolites TMAO, carnitine, γ-butyrobetaine, and crotonobetaine may be associated with insulin resistance, and betaine and choline may be associated with greater insulin sensitivity, but temporality of the associations was not established.

Project description:Type 2 diabetes mellitus (T2DM) is becoming a major contributor to cardiovascular disease. One of the early signs of T2DM associated cardiovascular events is the development of vascular dysfunction. This dysfunction has been implicated in increasing the morbidity and mortality of T2DM patients. One of the important characteristics of vascular dysfunction is the impaired ability of endothelial cells to produce nitric oxide (NO). Additionally, decreases in the availability of NO is also a major contributor of this pathology. NO is produced by the activity of endothelial NO synthase (eNOS) on its substrate, L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence, increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. Diabetes has been linked to elevated arginase and associated vascular endothelial dysfunction. We aimed to determine levels of plasma NO and arginase activity in (T2DM) patients and the effects of L-citrulline supplementation, a natural arginase inhibitor, on inhibiting arginase activity in these patients. Levels of arginase correlated with HbA1c levels in diabetic patients. Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway.

Dataset Information

Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes.

Publications

Inulin Supplementation Does Not Reduce Plasma Trimethylamine <i>N</i>-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes.

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