Circulating level of hepatocyte growth factor predicts incidence of type 2 diabetes mellitus: The Multi-Ethnic Study of Atherosclerosis (MESA)

Metabolism. 2016 Mar;65(3):64-72. doi: 10.1016/j.metabol.2015.10.023. Epub 2015 Oct 21.


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.

Keywords: Diabetes mellitus; Ethnicity; Hepatocyte growth factor; Incidence; Longitudinal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Atherosclerosis / epidemiology*
  • Biomarkers / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Ethnicity
  • Female
  • Glycated Hemoglobin / analysis
  • Hepatocyte Growth Factor / blood*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Sex Characteristics
  • Socioeconomic Factors
  • United States / epidemiology


  • Biomarkers
  • Glycated Hemoglobin A
  • HGF protein, human
  • Hepatocyte Growth Factor