title: The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients.
abstract: BACKGROUND
  Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events.
  
  
  METHODS
  We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery.
  
  
  RESULTS
  Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A(1c), and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001).
  
  
  CONCLUSIONS
  The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Greisa
authors.initials: G
authors.lastname: Vila
authors.forename: Michaela
authors.initials: M
authors.lastname: Riedl
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Michael
authors.initials: M
authors.lastname: Resl
authors.forename: Ammon
authors.initials: A
authors.lastname: Handisurya
authors.forename: Martin
authors.initials: M
authors.lastname: Clodi
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ludvik
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001837:Body Weights and Measures; D002319:Cardiovascular System / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005260:Female; D015390:Gastric Bypass; D005947:Glucose / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D007677:Kidney Function Tests; D050356:Lipid Metabolism; D008297:Male; D009767:Obesity, Morbid / Q000097:blood* / Q000150:complications / Q000601:surgery
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15; D003404:Creatinine; D005947:Glucose