Abstract 11733: Hepatocyte Growth Factor Resistance May Precede Development of Insulin Resistance in Humans: Prospective Study in a General Population

Abstract

OBJECTIVE: An HGF receptor forms a hybrid complex with an insulin receptor in the liver of mice, which leads to robust signaling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship of HGF with the development of insulin resistance (IR) in a general population without IR at baseline.

METHODS 1,492 subjects received health examinations. After excluding subjects with diabetes and/or IR (n=402) at baseline, the remaining subjects (n=1,090) were followed-up for 10 years. Complete datasets were available from 722 subjects for prospective analysis. We performed logistic regression analyses to determine factors associated with the development of IR. We divided baseline serum HGF levels into 4 categories and calculated relative risks for the development of IR after 10 years.

RESULTS In subjects without diabetes at baseline, serum HGF levels were higher (0.26±1.00ng/ml, n=259) in subjects with IR than without it (0.22±0.09ng/ml, n=1,090). Among subjects without IR at baseline (n=722), 192 subjects developed IR 10 years later. With multivariate logistic regression analysis, HGF (p<0.05), age (p<0.001), HOMA index (p<0.001), HDL-c (p<0.01; inversely) and hypertensive medication (p<0.01) were significantly associated with the development of IR. A significant (p<0.05) relative risk [1.77 (95% CI: 1.01-3.18)] for the development of IR was observed in the highest (≥0.30ng/ml) versus lowest categories (<0.15ng/ml) of HGF after adjustments for confounders.

CONCLUSION Our 10-year prospective study suggests that elevated serum HGF levels may precede the development of IR.