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The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis

Ramzan, Imran; Ardavani, Arash; Vanweert, Froukje; Mellett, Aisling; Atherton, Philip J.; Idris, Iskandar


Imran Ramzan

Arash Ardavani

Froukje Vanweert

Aisling Mellett

Professor of Clinical, metabolic & Molecular Physiology

Professor of Diabetes and Metabolic Medicine


Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored. Methods: A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Health and Care Excellence (NICE) website. The data sources included EMBASE, MEDLINE and PubMed for all papers from inception until November 2021. Nine studies were identified in this systematic review and meta-analysis. Stratification was based on follow-up times (0–6, 6–12 and 12 or more years) and controlling of body mass index (BMI) through the specific assessment of overweight cohorts was also undertaken. Results: The meta-analysis revealed a statistically significant positive association between BCAA concentrations and the development of T2DM, with valine OR = 2.08 (95% CI = 2.04–2.12, p < 0.00001), leucine OR = 2.25 (95% CI = 1.76–2.87, p < 0.00001) and isoleucine OR = 2.12, 95% CI = 2.00–2.25, p < 0.00001. In addition, we demonstrated a positive consistent temporal association between circulating BCAA levels and the risk of developing T2DM with differentials in the respective follow-up times of 0–6 years, 6–12 years and ≥12 years follow-up for valine (OR = 2.08, 1.86 and 2.14, p < 0.05 each), leucine (OR = 2.10, 2.25 and 2.16, p < 0.05 each) and isoleucine (OR = 2.12, 1.90 and 2.16, p < 0.05 each) demonstrated. Conclusion: Plasma BCAA concentrations are associated with T2DM incidence across all temporal subgroups. We suggest the potential utility of BCAAs as an early biomarker for T2DM irrespective of follow-up time.


Ramzan, I., Ardavani, A., Vanweert, F., Mellett, A., Atherton, P. J., & Idris, I. (2022). The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis. Nutrients, 14(20), Article 4411.

Journal Article Type Article
Acceptance Date Oct 11, 2022
Online Publication Date Oct 20, 2022
Publication Date Oct 1, 2022
Deposit Date Oct 12, 2022
Publicly Available Date Oct 12, 2022
Journal Nutrients
Electronic ISSN 2072-6643
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 14
Issue 20
Article Number 4411
Keywords Food Science; Nutrition and Dietetics
Public URL
Publisher URL


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