Abstract
Aims/hypothesisSouth Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures. Circulating amino acids (AAs) may provide additional explanatory insights. In a unique cohort of European and South Asian men, we compared cross-sectional associations between AAs, metabolic and obesity traits, and longitudinal associations with incident diabetes.MethodsNuclear magnetic spectroscopy was used to measure the baseline (1988–1991) levels of nine AAs in serum samples from a British population-based cohort of 1,279 European and 1,007 South Asian non-diabetic men aged 40–69 years. Follow-up was complete for 19 years in 801 European and 643 South Asian participants.ResultsThe serum concentrations of isoleucine, phenylalanine, tyrosine and alanine were significantly higher in South Asian men, while cross-sectional correlations of AAs with glycaemia and insulin resistance were similar in the two ethnic groups. However, most AAs were less strongly correlated with measures of obesity in the South Asian participants. Diabetes developed in 227 (35%) South Asian and 113 (14%) European men. Stronger adverse associations were observed between branched chain and aromatic AAs and incident diabetes in South Asian men. Tyrosine was a particularly strong predictor of incident diabetes in South Asian individuals, even after adjustment for metabolic risk factors, including obesity and insulin resistance (adjusted OR for a 1 SD increment, 1.47, 95% CI 1.17,1.85, p = 0.001) compared with Europeans (OR 1.10, 0.87, 1.39, p = 0.4; p = 0.045 for ethnicity × tyrosine interaction).Conclusions/interpretationBranched 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3517-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
Aims/hypothesis South Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures
The serum concentrations of isoleucine, phenylalanine, tyrosine and alanine were significantly higher in South Asian men, while cross-sectional correlations of amino acids (AAs) with glycaemia and insulin resistance were similar in the two ethnic groups
Serum samples were available for 1,279 European men and 1,007 South Asian men, of whom 801 (63%) Europeans and 643 (64%) South Asians had known follow-up information for diabetes status
Summary
1,007 South Asian non-diabetic men aged 40–69 years. South Asian migrant populations experience a greater burden of diabetes than their host populations of white European origin [2, 3]. The causal mechanisms underlying progression to type 2 diabetes remain poorly understood, and no study has yet compellingly explained the reasons for the excess risk of diabetes experienced by South Asian individuals, suggesting that complex metabolic disturbances may underlie the ethnic difference [3]. Many recent studies using metabolite profiling in European-origin populations have suggested five branched chain and aromatic amino acids (AAs) as predictors of insulin resistance and the future onset of type 2 diabetes [4,5,6,7,8,9]. A study of over 9,000 Finnish men revealed that increasing glycaemia was associated with increasing levels of six AAs (alanine, isoleucine, leucine, valine, phenylalanine and tyrosine) and with decreasing levels of
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