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Meta-Analysis
. 2022 Oct 20;14(20):4411.
doi: 10.3390/nu14204411.

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

Imran Ramzan  1   2 , Arash Ardavani  1   2 , Froukje Vanweert  3 , Aisling Mellett  1   4 , Philip J Atherton  1   2 , Iskandar Idris  1   2
Affiliations
Meta-Analysis

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

Imran Ramzan et al. Nutrients. .

Abstract

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.

Keywords: BCAA; BMI; T2DM; branch chain amino acid; insulin resistance; isoleucine; leucine; obese; obesity; overweight; type 2 diabetes mellitus; valine.

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Conflict of interest statement

Ramzan I: No disclosures. Ardavani A: No disclosures. Vanweert F: No disclosures. Mellett A: No disclosures. Atherton PJ: No disclosures. Idris I: No disclosures.

Figures

Figure 1
Figure 1
Forest plot depicting the effect sizes of the individual studies for valine in each of the designated temporal subgroups [29,30,31,41,42,43,44,45,46].
Figure 2
Figure 2
Forest plot depicting the effect sizes of the individual studies for leucine in each of the designated temporal subgroups [29,30,31,41,42,43,44,45,46].
Figure 3
Figure 3
Forest plot depicting the effect sizes of the individual studies for isoleucine in each of the designated temporal subgroups [29,30,31,41,42,43,44,45,46].
See this image and copyright information in PMC

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