title: Discriminative Ability of Plasma Branched-Chain Amino Acid Levels for Glucose Intolerance in Families At Risk for Type 2 Diabetes.
abstract: BACKGROUND
  Insulin resistance and glucose intolerance have been associated with increased plasma levels of branched-chain amino acids (BCAA). BCAA levels do not predict T2DM in the population. We determined the discriminative ability of fasting BCAA levels for glucose intolerance in nondiabetic relatives of patients with T2DM of two different ethnicities.
  
  
  METHODS
  Based on oral glucose tolerance test (OGTT), first-degree relatives of patients with T2DM were categorized as normal glucose tolerance, prediabetes, or T2DM. Included were 34, 12, and 18 Caucasian and 22, 12, and 23 Asian Indian participants, respectively. BCAA levels were measured in fasting plasma together with alanine, phenylalanine, and tyrosine. Insulin sensitivity and beta-cell function were assessed by indices derived from an extended OGTT and their relationship with plasma BCAA levels was assessed in multivariate regression analysis. The value of the amino acids for discriminating prediabetes among nondiabetic family members was determined with the area under the curve of receiver-operated characteristics (c-index).
  
  
  RESULTS
  BCAA levels were higher in diabetic than in normoglycemic family members in the Caucasians (P = 0.001) but not in the Asian Indians. In both groups, BCAA levels were associated with waist-hip ratio (β = 0.31; P = 0.03 and β = 0.42; P = 0.001, respectively) but not with indices of insulin sensitivity or beta-cell function. The c-index of BCAA for discriminating prediabetes among nondiabetic participants was 0.83 and 0.74 in Caucasians and Asian Indians, respectively, which increased to 0.84 and 0.79 by also including the other amino acids. The c-index of fasting glucose for discriminating prediabetes increased from 0.91 to 0.92 in Caucasians and 0.85 to 0.97 (P = 0.04) in Asian Indians by inclusion of BCAA+alanine, phenylalanine, and tyrosine.
  
  
  CONCLUSIONS
  Adding fasting plasma BCAA levels, combined with phenylalanine, tyrosine and alanine to fasting glucose improved discriminative ability for the prediabetic state within Asian Indian families at risk for T2DM. BCAA levels may serve as biomarkers for early development of glucose intolerance in these families.
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Sjaam
authors.initials: S
authors.lastname: Jainandunsing
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: J L Darcos
authors.initials: JL
authors.lastname: Wattimena
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Adrie J M
authors.initials: AJ
authors.lastname: Verhoeven
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Trinet
authors.initials: T
authors.lastname: Rietveld
authors.affiliation: 2 Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .|3 Center for Medical Systems Biology, Leiden, the Netherlands .
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Isaacs
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam , Rotterdam, the Netherlands .
authors.forename: Felix W M
authors.initials: FW
authors.lastname: de Rooij
mesh_terms: D000328:Adult; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000209:etiology*; D003937:Diagnosis, Differential; D003940:Diagnostic Techniques, Endocrine; D005190:Family; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis / Q000208:ethnology; D012307:Risk Factors
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers