title: Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes.
abstract: BACKGROUND
  Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT.
  
  
  RESULTS
  Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 μmol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis.
  
  
  CONCLUSIONS
  These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.forename: Kun-Tai
authors.initials: KT
authors.lastname: Lee
authors.forename: Kai-Hong
authors.initials: KH
authors.lastname: Cheng
authors.forename: Min-Yi
authors.initials: MY
authors.lastname: Lee
authors.forename: Hsuan-Fu
authors.initials: HF
authors.lastname: Kuo
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
authors.forename: Ho-Ming
authors.initials: HM
authors.lastname: Su
authors.forename: Wen-Chol
authors.initials: WC
authors.lastname: Voon
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D048909:Diabetes Complications / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011236:Prediabetic State / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine