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.
Bibliographical noteFunding Information:
M.P.B. was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL007779 to conduct the current work. The Multi-Ethnic Study of Atherosclerosis is conducted and supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from National Center for Research Resources. Adhesion protein measurements supported by Multi-scale Biology of Atherosclerosis in the Cellular Adhesion Pathway (HL98077). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- Diabetes mellitus
- Hepatocyte growth factor