title: 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.
abstract: OBJECTIVE
  South 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.
  
  
  METHODS
  Nuclear 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.
  
  
  RESULTS
  The 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
  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.
authors.affiliation: UCL Institute of Cardiovascular Science, 170 Tottenham Court Road, London, W1T 7HA, UK, t.tillin@ucl.ac.uk.
authors.forename: Therese
authors.initials: T
authors.lastname: Tillin
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
authors.forename: Ian F
authors.initials: IF
authors.lastname: Godsland
authors.forename: Sophie V
authors.initials: SV
authors.lastname: Eastwood
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: Nish
authors.initials: N
authors.lastname: Chaturvedi
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood*; D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D044465:White People
chemical_list: D000596:Amino Acids; D001786:Blood Glucose