- Marta Guasch-Ferré et al. Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis. Diabetes Care. 2016 May; 39(5): 833–846.
In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
- Jeong-Eun Park et al. Metabolite changes in risk of type 2 diabetes mellitus in cohort studies: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2018 Jun; 140:216-227.
Most amino acids in patients were positively related to diabetes, while creatinine and some lysophosphatidylcholines showed a negative relationship. This suggests that diabetic risk prediction using metabolites that sensitively reflect changes in the body will improve individual diagnosis and personalize medicine.
- Jianglan Long et al. Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis. BMC Endocr Disord. 2020; 20: 174
Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM.
A combination of three amino acids predicted future diabetes (with a more than fivefold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.
- Jose L Flores-Guerrero et al. Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study. J Clin Med. 2018 Dec 4;7(12):513.
In conclusions, high concentrations of BCAAs associate with insulin resistance and with increased risk of type 2 diabetes. This association is independent of multiple risk factors, HOMA-IR and β cell function.
- Sanmei Chen et al. Serum amino acid profiles and risk of type 2 diabetes among Japanese adults in the Hitachi Health Study. Sci Rep. 2019 May 7;9(1):7010.
High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms.
- Ari V. Ahola-Olli et al. Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia. 2019; 62(12): 2298–2309.
Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.
- Drábková P . An Assay of Selected Serum Amino Acids in Patients with Type 2 Diabetes Mellitus. Adv Clin Exp Med. 2015 May-Jun;24(3):447-51
Significant difference in metabolism of amino acids between diabetics and non-diabetics were observed. The altered levels of amino acids in diabetic patients could be a suitable predictor of diabetes.
- TillinT. Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall and Brent REvisited) Study. Diabetologia. 2015 May;58(5):968-79.
Branched chain and aromatic AAs, particularly tyrosine, may be a focus for identifying novel aetiological mechanisms and potential treatment targets for diabetes in South Asian populations and may contribute to their excess risk of diabetes
- Wang-Sattler R. Novel biomarkers for pre-diabetes identified by metabolomics. Mol Syst Biol. 2012; 8 : 615.
Our study revealed significant metabolic variation in pre-diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated haemoglobin levels, fasting glucose and insulin. Our results may help developing novel strategies to prevent T2D.
- Peter Würtz et al. Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women. Diabetes Care. 2012 Aug; 35(8): 1749–1756.
Alterations in branched-chain and aromatic amino acid metabolism precede hyperglycaemia in the general population. Further, alanine, lactate, and pyruvate were predictive of post challenge glucose exclusively. These gluconeogenic precursors are potential markers of long-term impaired insulin sensitivity that may relate to attenuated glucose tolerance later in life.
- C Gar et al. Serum and plasma amino acids as markers of prediabetes, insulin resistance, and incident diabetes. Crit Rev Clin Lab Sci. 2018 Jan;55(1):21-32.
The identification of more precise intermediates of amino acid metabolism or combinations with other biomarkers will, therefore, be necessary to obtain in order to develop laboratory tests that can improve T2D screening.
- Giesbertz P. Branched-chain amino acids as biomarkers in diabetes. Curr Opin Clin Nutr Metab Care. 2015 Oct 20.
Understanding the mechanisms and putative causalities in the alterations in BCAA levels as found in obesity, metabolic syndrome and diabetes is crucial for any intervention options but also for the use of BCAA and derivatives as biomarkers in clinical routine.