The Emerging role of Branch Chain Amino Acids in the Prediction of Diabetes: A Brief Review

Author(s): Shaik Sarfaraz Nawaz, Khalid Siddiqui*

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 6 , 2020

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Diabetes is a chronic condition; those with diabetes are at high risk of developing diabetes complications. One important approach to tackle the diabetes burden is to screen for undiagnosed diabetes and to identify factors that lead to the risk of developing diabetes in the future. The earlier identification of individuals at risk of developing diabetes is crucial for delaying or preventing the onset of type 2 diabetes. Numerous studies have demonstrated that circulating concentrations of branch chain amino acids (BCAAs) predict the risk for developing diabetes; thus, contributing to the recent resurgence of interest in these common analytes. The present review aimed to address the recent findings regarding BCAAs and their role in insulin resistance and diabetes. Recent studies demonstrate that BCAAs are strongly associated with a number of pathological mechanisms causing insulin resistance and type 2 diabetes. The research findings related to BCAA signaling pathways and metabolism broaden our understanding of this topic. However, it remains unclear how increased levels of BCAAs will assist in the prediction of future insulin resistance or type 2 diabetes. Future research needs to determine whether BCAAs are a causative factor for insulin resistance and type 2 diabetes, or just a biomarker of impaired insulin action.

Keywords: Branch chain amino acids, type 2 diabetes, insulin resistance, diabetes mellitus, biomarkers, glucose levels.

International Diabetes Federation IDF diabetes atlas 8th edition:International Diabetes Federation. 2107. (Accessed on: October 25, 2018)
Tabák AG, Jokela M, Akbaraly TN, Brunner EJ, Kivimäki M, Witte DR. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009; 373(9682): 2215-21.
[] [PMID: 19515410]
Monirujjaman M, Ferdouse A. Metabolic and physiological roles of branched-chain amino acids. Adv Mol Biol 2014.
Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol 2014; 10(12): 723-36.
[] [PMID: 25287287]
Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med 2011; 17(4): 448-53.
[] [PMID: 21423183]
Ardestani A, Lupse B, Kido Y, Leibowitz G, Maedler K. mTORC1 signaling: a double-edged sword in diabetic β cells. Cell Metab 2018; 27(2): 314-31.
[] [PMID: 29275961]
Gannon NP, Schnuck JK, Vaughan RA. BCAA metabolism and insulin sensitivity–Dysregulated by metabolic status? Mol Nutr Food Res 2018; 62(6)e1700756
[] [PMID: 29377510]
Stancáková A, Civelek M, Saleem NK, et al. Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. Diabetes 2012; 61(7): 1895-902.
[] [PMID: 22553379]
Merino J, Leong A, Liu CT, et al. Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose. Diabetologia 2018; 61(6): 1315-24.
[] [PMID: 29626220]
Mahendran Y, Jonsson A, Have CT, et al. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels. Diabetologia 2017; 60(5): 873-8.
[] [PMID: 28184960]
Wang Q, Holmes MV, Davey Smith G, Ala-Korpela M. Genetic support for a causal role of insulin resistance on circulating branched-chain amino acids and inflammation. Diabetes Care 2017; 40(12): 1779-86.
[] [PMID: 29046328]
Ruiz-Canela M, Guasch-Ferré M, Toledo E, et al. Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial. Diabetologia 2018; 61(7): 1560-71.
[] [PMID: 29663011]
Wang S, Yu X, Zhang W, et al. Association of serum metabolites with impaired fasting glucose/diabetes and traditional risk factors for metabolic disease in Chinese adults. Clin Chim Acta 2018; 487: 60-5.
[] [PMID: 30237081]
Lee CC, Watkins SM, Lorenzo C, et al. Branched-chain amino acids and insulin metabolism: The Insulin Resistance Athero-sclerosis Study (IRAS). Diabetes Care 2016; 39(4): 582-8.
[] [PMID: 26895884]
Yamakado M, Nagao K, Imaizumi A, et al. Plasma free amino acid profiles predict four-year risk of developing diabetes, metabolic syndrome, dyslipidemia, and hypertension in Japa-nese population. Sci Rep 2015; 5: 11918.
[] [PMID: 26156880]
Yamada C, Kondo M, Kishimoto N, et al. Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects. J Diabetes Investig 2015; 6(4): 408-15.
[] [PMID: 26221519]
Nakamura H, Jinzu H, Nagao K, et al. Plasma amino acid profiles are associated with insulin, C-peptide and adiponectin levels in type 2 diabetic patients. Nutr Diabetes 2014. 4e133
[] [PMID: 25177913]
McCormack SE, Shaham O, McCarthy MA, et al. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes 2013; 8(1): 52-61.
[] [PMID: 22961720]
Würtz P, Soininen P, Kangas AJ, et al. Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 2013; 36(3): 648-55.
[] [PMID: 23129134]
Magnusson M, Lewis GD, Ericson U, et al. A diabetes-predictive amino acid score and future cardiovascular disease. Eur Heart J 2013; 34(26): 1982-9.
[] [PMID: 23242195]
Würtz P, Tiainen M, Mäkinen VP, et al. Circulating metabolite predictors of glycemia in middle-aged men and women. Diabetes Care 2012; 35(8): 1749-56.
[] [PMID: 22563043]
Würtz P, Mäkinen VP, Soininen P, et al. Metabolic signatures of insulin resistance in 7,098 young adults. Diabetes 2012; 61(6): 1372-80.
[] [PMID: 22511205]
Newgard CB, An J, Bain JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009; 9(4): 311-26.
[] [PMID: 19356713]
Azuma Y, Maekawa M, Kuwabara Y, Nakajima T, Taniguchi K, Kanno T. Determination of branched-chain amino acids and tyrosine in serum of patients with various hepatic diseases, and its clinical usefulness. Clin Chem 1989; 35(7): 1399-403.
[] [PMID: 2758584]
Song C, Zhang S, Ji Z, Li Y, You J. Accurate determination of amino acids in serum samples by liquid chromatography–tandem mass spectrometry using a stable isotope labeling strategy. J Chromatogr Sci 2015; 53(9): 1536-41.
[] [PMID: 25940231]
Sun L, Jiao H, Gao B, et al. Hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method for the simultaneous determination of l-valine, l-leucine, l-isoleucine, l-phenylalanine, and l-tyrosine in human serum. J Sep Sci 2015; 38(22): 3876-83.
[] [PMID: 26377247]
Wolak-Dinsmore J, Gruppen EG, Shalaurova I, et al. A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness. Clin Biochem 2018; 54: 92-9.
[] [PMID: 29432757]

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Article Details

Year: 2020
Page: [532 - 537]
Pages: 6
DOI: 10.2174/1573399815666190502113632
Price: $65

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