Dataset Information

Fasting status and metabolic health in relation to plasma branched chain amino acid concentrations in women.

ABSTRACT:

Background

Circulating branched chain amino acids (BCAA) are associated with cardiometabolic risk, although the mechanisms leading to their accumulation remain uncertain. Examining the relationship between fasting status, metabolic syndrome, and type 2 diabetes (T2D) with circulating BCAA levels may provide insights into their metabolic handling.

Methods

We conducted cross-sectional analyses among 25,740 Women's Health Study participants (mean age 55 years).

Results

In multivariable linear regression models, fasting was associated with lower plasma BCAAs vs. non-fasting in women without metabolic syndrome or T2D (% mean difference = -5.1%; 95% CI = -5.8, -4.5) and among women with metabolic syndrome only (-3.7%; -4.9, -2.6), p_interaction = 0.002. However, there was no difference in BCAAs by fasting status among women with T2D (0.4%; -3.7, 4.7).

Conclusions

We observed higher BCAAs with worsening metabolic health status. Fasting is modestly associated with lower plasma BCAAs, except among women with T2D. These findings support hypotheses that impaired BCAA catabolism may be a feature of T2D pathophysiology.

SUBMITTER: Tobias DK

PROVIDER: S-EPMC7985990 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Fasting status and metabolic health in relation to plasma branched chain amino acid concentrations in women.

Tobias Deirdre K DK Mora Samia S Verma Subodh S Billia Filio F Buring Julie E JE Lawler Patrick R PR

Metabolism: clinical and experimental 20201015

<h4>Background</h4>Circulating branched chain amino acids (BCAA) are associated with cardiometabolic risk, although the mechanisms leading to their accumulation remain uncertain. Examining the relationship between fasting status, metabolic syndrome, and type 2 diabetes (T2D) with circulating BCAA levels may provide insights into their metabolic handling.<h4>Methods</h4>We conducted cross-sectional analyses among 25,740 Women's Health Study participants (mean age 55 years).<h4>Results</h4>In mult ...[more]

PMID: 33069808

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Project description:BackgroundCirculating branched-chain amino acids (BCAAs-isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however, determinants of elevated fasting BCAA concentrations are largely unknown.ObjectivesWe aimed to characterize the modifiable lifestyle factors related to plasma BCAAs.MethodsWe performed a cross-sectional analysis among n = 18,897 women (mean ± SD age: 54.9 ± 7.2 y) in the Women's Health Study, free of T2D and cardiovascular disease at baseline blood draw. Lifestyle factors, weight, and height were self-reported via questionnaire, including smoking status, alcohol, leisure-time physical activity (LTPA), diet quality scores [2010 Alternative Healthy Eating Index (without alcohol) (aHEI); alternate Mediterranean Diet (aMED)], and dietary sources of BCAAs. Plasma BCAAs were quantified via NMR spectroscopy. We calculated multivariable-adjusted percentage mean differences (95% CIs) and P values for linear trend of BCAAs stratified by categoric lifestyle factors. We estimated R2 from univariate cubic spline regression models to estimate the variability in BCAAs explained.ResultsCompared with women with BMI (in kg/m2) <25.0, BCAAs were 8.6% (95% CI: 8.0%, 9.3%), 15.3% (95% CI: 14.4%, 16.3%), and 21.0% (95% CI: 18.2%, 23.9%) higher for the BMI strata 25.0-29.9, 30.0-39.9, and ≥40.0, respectively (P-trend < 0.0001). Women with higher LTPA and higher alcohol intake compared with lower had modestly (∼1%) lower plasma BCAAs (P-trend = 0.014 and 0.0003, respectively). Differences in smoking status, aHEI, and aMED score were not related to plasma BCAAs. Women with higher dietary BCAAs had dose-response higher plasma BCAA concentrations, 3.4% (95% CI: 2.5%, 4.4%) higher when comparing the highest with the lowest quintile (P-trend < 0.0001). BMI explained 11.6% of the variability of BCAAs, whereas other factors explained between 0.1% and 1%.ConclusionsOur findings among a large cohort of US women indicate that BMI, but less so diet, physical activity, and other lifestyle factors, is related to plasma BCAAs.This trial was registered at clinicaltrials.gov as NCT00000479.

Project description:BackgroundBranched-chain amino acids (BCAAs; isoleucine, leucine, and valine) correlate with insulin resistance and poor glucose control, which may in part explain associations between type 2 diabetes and cardiovascular disease. However, the relationships of BCAAs with other cardiometabolic pathways, including inflammation and dyslipidemia, are unclear. We hypothesized that plasma BCAAs would correlate with multiple pathways of cardiometabolic dysfunction.MethodsWe conducted a cross-sectional analysis among 19 472 participants (mean age=54.9 years, SD=7.2 years) in the Women's Health Study without a history of type 2 diabetes, cardiovascular disease, or cancer. We quantified the concentrations of individual biomarkers of inflammation and lipids, across quartiles of BCAAs, adjusting for age, smoking, body mass index, physical activity, and other established cardiovascular disease risk factors at blood draw.ResultsWomen in the highest versus lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (multivariable-adjusted means: 1.96 versus 1.43 mg/L), fibrinogen (367 versus 362 mg/dL), soluble intercellular cell adhesion molecule-1 (361 versus 353 ng/mL), and glycoprotein acetylation (407 versus 371 µmol/L; P trend=0.0002 for fibrinogen; P<0.0001 for others). Similarly for lipids, women with higher BCAAs had lower HDL-C (high-density lipoprotein cholesterol; 49.0 versus 55.0 mg/dL), and higher triglycerides (143 versus 114 mg/dL), LDL-C (low-density lipoprotein cholesterol; 133 versus 124 mg/dL), and lipoprotein insulin resistance score (52.6 versus 37.3; all: P<0.0001). Similar associations with these biomarkers were observed in isoleucine, leucine, and valine, respectively.ConclusionsHigher circulating BCAA concentrations are associated with adverse profiles of biomarkers of inflammation and dyslipidemia independent of established cardiovascular disease risk factors, and thus, may reflect poorer cardiometabolic health through multiple pathways. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000479.

Dataset Information

Fasting status and metabolic health in relation to plasma branched chain amino acid concentrations in women.

Background

Methods

Results

Conclusions

Publications

Fasting status and metabolic health in relation to plasma branched chain amino acid concentrations in women.

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