title: Circulating level of hepatocyte growth factor predicts incidence of type 2 diabetes mellitus: The Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is a pleotropic factor posited to have metabolic homeostatic properties. The purpose of this study is to examine whether level of HGF is associated with the development of type 2 diabetes.
  
  
  METHODS
  Data from the Multi-Ethnic Study of Atherosclerosis (MESA) were used to examine the prospective association between serum level of HGF and incident diabetes. Fasting HGF was measured at Exam 1 (2000-2002) in 5395 participants free from diabetes (61.5±10.2 years old) and incidence of diabetes was determined at four subsequent follow-up exams over 12 years. Hazard ratios (HR) for incident diabetes were estimated according to 1 standard deviation (SD) unit increment of HGF (1 SD=26 μg/l), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, body mass index, waist circumference, fasting glucose and insulin, C-reactive protein, and interleukin-6 levels.
  
  
  RESULTS
  A 1 SD increment of baseline HGF was associated with a 46% (95% CI=1.37, 1.56) increased risk of diabetes before adjustment. After adjustment, diabetes risk per 1 SD increment of HGF was attenuated but remained significantly increased (HR=1.21; 95% CI=1.12, 1.32). Men had a significantly greater HR compared to women per equivalent increase of HGF (p-value for sex interaction=0.04). There was no evidence of effect modification by race/ethnicity.
  
  
  CONCLUSIONS
  This study advances understanding from cross-sectional studies and investigation of incident insulin resistance, demonstrating higher level of HGF is associated with incident diabetes and may reflect a unique type of impaired metabolism.
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: banck001@umn.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bancks
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Bielinski.Suzette@mayo.edu.
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Decker.Paul@mayo.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: hanso047@umn.edu.
authors.forename: Naomi Q
authors.initials: NQ
authors.lastname: Hanson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Larson.Nicholas@mayo.edu.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Larson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Sicotte.Hugues@mayo.edu.
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Colchester, VT, 05446, USA. Electronic address: cwassel@med.uvm.edu.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: panko001@umn.edu.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000453:epidemiology; D005006:Ethnicity; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012727:Sex Characteristics; D012959:Socioeconomic Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D017228:Hepatocyte Growth Factor; C066855:HGF protein, human
keywords: Diabetes mellitus; Ethnicity; Hepatocyte growth factor; Incidence; Longitudinal