Dataset Information

Branched-Chain Amino Acids Associate Negatively With Postprandial Insulin Secretion in Recent-Onset Diabetes.

ABSTRACT:

Context

In addition to unfavorable effects on insulin sensitivity, elevated plasma branched-chain amino acids (BCAA) stimulate insulin secretion, which, over the long-term, could impair pancreatic β-cell function.

Objective

To investigate cross-sectional and prospective associations between circulating BCAA and postprandial β-cell function in recently diagnosed type 1 and type 2 diabetes.

Methods

The study included individuals with well-controlled type 1 and type 2 diabetes (known diabetes duration <12 months) and glucose-tolerant participants (controls) of similar age, sex, and body mass index (n = 10/group) who underwent mixed meal tolerance tests. Plasma BCAA levels were quantified by gas chromatography-mass spectrometry, postprandial β-cell function was assessed from serum C-peptide levels, and insulin sensitivity was determined from PREDIM index (PREDIcted M-value).

Results

In type 1 diabetes, postprandial total BCAA, valine, and leucine levels were 25%, 18%, and 19% higher vs control, and total as well as individual postprandial BCAA were related inversely to C-peptide levels. In type 2 diabetes, postprandial isoleucine was 16% higher vs the respective controls, while neither total nor individual BCAA correlated with C-peptide levels. Whole-body insulin sensitivity was lower in both diabetes groups than in corresponding controls.

Conclusion

Insulin deficiency associates with sustained high BCAA concentrations, which could contribute to exhausting the insulin secretory reserve in early type 1 diabetes.

SUBMITTER: Karusheva Y

PROVIDER: S-EPMC8130764 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCirculating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear.MethodsWe evaluated circulating BCAA levels and breast cancer risk within the Nurses' Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women's Health Study (WHS). All statistical tests were 2-sided.ResultsAmong NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, P trend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, P trend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, P trend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, P trend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, P trend = .04).ConclusionsNo statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.