Association Of Type 2 Diabetes Mellitus With Hepatocellular Carcinoma And Alpha Fetal Protein

Purpose: A large number of epidemiological data indicate that diabetes mellitus is a risk factor for the development of hepatocellular carcinoma(HCC).As an important tumor marker of hepatocellular carcinoma,alpha fetal protein(AFP),its association with diabetes is not clear yet,with few data.In this study,serum AFP levels in patients with type 2 diabetes mellitus(T2DM)and patients with HCC were analyzed to explore the association of T2DM with HCC and serum AFP.Methods: A total of 800 healthy people(control group),750 non-tumor patients with T2DM(T2DM group)and 501 patients newly diagnosed with HCC in Shanghai Tenth People's Hospital were recruited from 2010 to 2016.The HCC patients were further divided into an HCC with T2DM(HCC+T2DM)group and an HCC without diabetes mellitus(HCC+NDM)group.Age,height,weight,fasting blood glucose(FPG),glycosylated hemoglobin A1c(Hb A1c),duration of diabetes,liver function,AFP level,pathological grade of HCC were recorded.The multivariate logistic regression and covariance analysis were applied to investigate the relationship of T2DM with HCC and AFP.Results: 1.Compared to the healthy control group,the T2DM group had lower AFP level(Ln AFP: 0.87 vs.0.73,P<0.001).Serum AFP level was inversely correlated to age and duration of diabetes(r=-0.147,P<0.001;r=-0.180,P<0.001).For the T2DM group,the distribution of AFP level in age and duration of diabetes had significant differences(P<0.001;P<0.001),while there was no obvious trend along these subgroups.2.Of 501 HCC patients,230(45.91%)had T2DM.When compared to the HCC+NDM group,the HCC+T2DM group had a higher negative rate of AFP(55.22%(127)vs.37.26%(101),c(17)=15.45,P<0.001),worse liver function(c(17)=9.58,P=0.008)and a lower AFP level(Ln AFP: 3.24 vs.4.29,P<0.001).3.T2DM significantly increased the risk of high-grade(grade 3 and 4)HCC(OR=1.95,95% CI: 1.10-3.02,P=0.029).4.In HCC patients,Serum AFP level was inversely correlated to age and T2DM(r=-0.162,P=0.001;r=-0.167,P=0.002).5.In the HCC+T2DM group,the distribution of AFP level in BCLC stages and pathology grades had significant differences(P=0.008;P<0.001),while there was no obvious trend along these subgroups.Conclusion: T2DM was associated with lower AFP level,worse liver function and higher risk of high-grade HCC.We speculated that low AFP levels in diabetics might delay and interfere with HCC diagnosis,leading to higher degree of malignant HCC,especially for the elderly and patients with long duration.