Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort

Lever, Michael; George, Peter M.; Atkinson, Wendy; Molyneux, Sarah L.; Elmslie, Jane; Slow, Sandy; Richards, A. Mark; Chambers, Stephen T.

doi:10.1371/journal.pone.0021666

Cited by 50 publications

(57 citation statements)

References 38 publications

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“…Associations of choline and betaine with diabetes have also been made by several groups [42, 53, 56, 57]. Moreover, several studies have observed increased levels of choline and betaine associated with the increased incidence of coronary syndrome as well as increased blood lipid levels [39, 40, 42, 58–62]. This provides evidence for the relationship between choline and betaine with diabetes and cardiovascular health.…”

Section: Microbiota Produced Metabolites and The Evolving Relationshimentioning

confidence: 55%

Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis

Kirsop

Tang

2015

Curr Diab Rep

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What we understand about diabetes from decades of genetics research is now being supplemented with exciting new evidence based on a better understanding of how one of the biggest “environmental” factors the body is exposed to is influencing the pathogenesis of disease. The recent discovery that certain dietary nutrients possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and L-carnitine) participate in the development of atherosclerotic heart disease has renewed attention towards the contributions of gut microbiota in the development of cardiovascular diseases. Collectively, animal and human studies reveal that conversion of these nutrient precursors to trimethylamine N-oxide (TMAO) depends on both microbial composition and host factors, and can be induced by dietary exposures. In addition, circulating TMAO levels are strongly linked to cardiovascular disease risks and various adverse cardio-renal consequences. Our group and others have further demonstrated that circulating TMAO levels are elevated in patients with type 2 diabetes mellitus compared to healthy controls and gut microbiota-dependent phosphatidylcholine metabolism has been implicated in metabolic dysregulation and insulin resistance in animal models. Therefore, preventive strategies to minimize adverse consequences associated with TMAO generation in the diabetic population are warranted.

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Section: Microbiota Produced Metabolites and The Evolving Relationshimentioning

confidence: 55%

Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis

Kirsop

Tang

2015

Curr Diab Rep

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“…For example, a study of a cohort with acute coronary syndrome concluded that high and low plasma betaine concentrations were associated with increased risks of secondary heart failure and acute myocardial infarction, respectively (24). A second study in the same cohort concluded that lower plasma betaine concentrations were associated with higher concentrations of triglycerides and non-HDL cholesterol (25). In contrast, in the NAME population, although there was an inverse relation between plasma betaine and both LDL-cholesterol and triglyceride concentrations, there was no significant relation between plasma betaine concentrations and odds of cardiovascular or cerebrovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults,

Roe

Zhang

Bhadelia

et al. 2017

The American Journal of Clinical Nutrition

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Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology. Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean 6 SD age: 73 6 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilutionmultiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small-and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology. Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower highdensity lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile (higher LDL cholesterol and triglycerides). Conclusion: Choline and its metabolites have differential associations with cardiometabolic risk factors and subtypes of vascular disease, thereby suggesting differing roles in the pathogenesis of cardiovascular and cerebral large-vessel disease compared with that of small-vessel disease.Am J Clin Nutr 2017;105:1283-90.

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“…Participants were also excluded if their glycated haemoglobin (HbA 1c ) was >9.5% (80 mmol/mol) or they had had renal disease (estimated glomerular filtration rate [eGFR] <60 ml/min/ 1.73 m 2 or urine albumin:creatinine ratio [UACR] >30 mg/mmol), abnormal liver enzymes, heart failure, known active malignancy or myocardial infarction in the preceding six months. Details of variables such as weight, plasma glucose, HbA 1c and markers of renal failure throughout the study were previously reported by Krebs et al 12 Because fibrates have been associated with increased urinary betaine excretion, [13][14][15] subjects who were on fibrate therapy were excluded from the analysis. …”

Section: Methodsmentioning

confidence: 99%

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

et al. 2014

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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.

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Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort

Cited by 50 publications

References 38 publications

Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis

Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults,

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

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