Michael P Bancks1, Suzette J Bielinski2, Paul A Decker3, Naomi Q Hanson4, Nicholas B Larson5, Hugues Sicotte6, Christina L Wassel7, James S Pankow8. 1. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: banck001@umn.edu. 2. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Bielinski.Suzette@mayo.edu. 3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Decker.Paul@mayo.edu. 4. Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: hanso047@umn.edu. 5. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Larson.Nicholas@mayo.edu. 6. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: Sicotte.Hugues@mayo.edu. 7. Department of Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Colchester, VT, 05446, USA. Electronic address: cwassel@med.uvm.edu. 8. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 55454, USA. Electronic address: panko001@umn.edu.
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.
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.
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