ArticleThe American journal of clinical nutrition2023
Mixed meal tolerance testing highlights in diabetes altered branched-chain ketoacid metabolism and pathways associated with all-cause mortality.
Article in The American journal of clinical nutrition, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed, 4 citations in OpenAlex.
- Quantitation of BCAA and BCKA in plasma and patient-centric dried blood microsamples in a clinical setting.Bioanalysis · 2025Article
- Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity.Cell metabolism · 2024Article
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundElevated BCAA levels are strongly associated with diabetes, but how diabetes affects BCAA, branched-chain ketoacids (BCKAs), and the broader metabolome after a meal is not well known.
objectiveTo compare quantitative BCAA and BCKA levels in a multiracial cohort with and without diabetes after a mixed meal tolerance test (MMTT) as well as to explore the kinetics of additional metabolites and their associations with mortality in self-identified African Americans.
methodsWe administered an MMTT to 11 participants without obesity or diabetes and 13 participants with diabetes (treated with metformin only) and measured the levels of BCKAs, BCAAs, and 194 other metabolites at 8 time points across 5 h. We used mixed models for repeated measurements to compare between group metabolite differences at each timepoint with adjustment for baseline. We then evaluated the association of top metabolites with different kinetics with all-cause mortality in the Jackson Heart Study (JHS) (N = 2441).
resultsBCAA levels, after adjustment for baseline, were similar at all timepoints between groups, but adjusted BCKA kinetics were different between groups for α-ketoisocaproate (P = 0.022) and α-ketoisovalerate (P = 0.021), most notably diverging at 120 min post-MMTT. An additional 20 metabolites had significantly different kinetics across timepoints between groups, and 9 of these metabolites-including several acylcarnitines-were significantly associated with mortality in JHS, irrespective of diabetes status. The highest quartile of a composite metabolite risk score was associated with higher mortality (HR:1.57; 1.20, 2.05, P = 0.00094) than the lowest quartile.
conclusionsBCKA levels remained elevated after an MMTT among participants with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the interaction of BCAA and diabetes. Metabolites with different kinetics after an MMTT may be markers of dysmetabolism and associated with increased mortality in self-identified African Americans.
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