Elevated fasting serum glucose levels increase the risk of hepatocellular carcinoma: A prospective cohort study

Abstract

Previous studies have demonstrated a positive relationship between liver cancer and diabetes mellitus. However, elevated fasting blood glucose (FBG) itself may be a risk factor for the development of hepatocellular carcinoma (HCC) rather than diabetes, and during the follow-up period, death is an event thatmay occurbefore the occurrence ofHCC, which should be dealt with competing riskmodels. Our study aims to investigate the relationship between FBG and new-onset HCC by using competing risk regression models. We prospectively studied the relationship between FBG concentrations and risk of HCC in a cohort of 93, 447 participants who were free of prior HCC, and whose demographic characteristics and biochemical parameters were recorded. Cox proportional hazards regression models and competing risk regression models were used to evaluate the association between FBG concentrations and risk of incident HCC. A total of 302 participants were diagnosed with HCC among 93, 447 subjects during 810, 499 person-years of follow-up. The multivariable hazard ratios (HRs) [95% confidence interval (95% CI)] for the association of FBG and log(FBG) with HCC were 1.07 (1.01~1.12), 1.84 (1.23~2.74) in an analysis adjusted for other potential variables. In the multivariable adjusted analysis, participants who were in 4.82mmol/L≤FBG≤5.49mmol/L group and FBG >5.49mmol/L group would have increased the risk of HCC by 47% and 69%, respectively. In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of FBG with HCC were 1.46 (1.09~1.98), 1.69 (1.27~2.27) in the multivariable adjusted analysis. Similar results were also observed in subdistribution hazard function model (SD model) with corresponding multivariate HRs (95% CI) of 1.46 (1.09~2.00), 1.69 (1.25~2.27) in 4.82mmol/L≤FBG≤5.49mmol/L group and FBG >5.49mmol/L group, respectively. Higher FBG concentrations itself were positively associated with new-onset HCC in the Cox proportional hazards regressionmodels and competing risk models. FBGconcentrations can be used as a scientific and important way to identify individuals with a higher risk of HCC and control of FBG concentrations might serve as a possible way to decrease the risk of HCC among Chinese population. Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered). Abbreviations: ALT = alanine aminotransferase, ANOVA = one-way analysis of variance, BMI = body mass index, CI = confidence interval, CS model = cause-specific hazard model, FBG = fasting blood glucose, GDNF = glial cell derived neurotrophic factor, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, HCV = hepatitis C virus, HDL-C = high-density lipoprotein cholesterol, HRs = hazard ratios, IGF-I = insulin-like growth factor -1, LDL-C = low-density lipoprotein cholesterol, NAFLD = nonalcoholic fatty liver disease, NASH = nonalcoholic steatohepatitis, RCS = restricted cubic spline regression, SD model = subdistribution hazard function model, WC = waist circumference.