2型糖尿病与原发性肝癌及血清甲胎蛋白的相关性

Association of type 2diabetes mellitus with hepatocellular carcinoma and alpha fetal protein

目的 探讨2型糖尿病与原发性肝癌(HCC)及血清甲胎蛋白(AFP)之间的关联.方法回顾性分析2010年1月至2016年12月期间收治的508例[年龄(59±12)岁,男性406例(79.92%)]初诊HCC患者的空腹血糖、肝功能指标、AFP等资料.将所有研究对象分为2型糖尿病组(n=233)和非糖尿病组(n=275),肝功能分级依据Child-Pugh分级标准分为A、B、C级,肝癌病理分级根据Edmondson-Steiner标准分为1~4级,肝癌临床分期根据巴塞罗那分期分为0~4期,年龄按<50岁、50~59岁、60~69岁、≥70岁分为4组.分析HCC合并糖尿病患者血清AFP水平的特点,采用多元Logistic回归、线性回归、协方差分析分别探讨2型糖尿病与HCC和血清AFP水平的关联.结果与非糖尿病组相比,糖尿病组AFP阴性率显著升高[54.51%(127/233)比37.82%(104/275),χ^2=14.17,P<0.001],AFP水平显著降低[11(4~249)比89(8~1132)μg/L,Z=-4.32,P<0.001],肝功能分级更差(χ^2=9.60,P=0.012);校正年龄等混杂因素后,糖尿病组AFP水平仍显著低于非糖尿病组(H=10.15,P=0.002).2型糖尿病显著增加高级别(3、4级)肝癌患病风险(OR=1.80,95%CI 1.08~3.00,P=0.025).在HCC人群中AFP水平与2型糖尿病和年龄呈负相关(β=-0.151,P=0.001;β=-0.162,P=0.003).结论2型糖尿病患者AFP阴性率升高,AFP水平降低,可能延误HCC的早期诊断,导致高级别肝癌患病风险增加.

Objective To investigate the relationship of type 2 diabetes mellitus with hepatocellular carcinoma (HCC) and alpha fetal protein (AFP). Methods A total of 508 patients [(59 ± 12) years old, 406 males (79.92%)] with HCC from January 2010 to December 2016 were retrospectively evaluated. All patients were divided into type 2 diabetic group (n=233) and non-diabetic group (n=275). Fasting blood glucose, liver function and AFP level were compared and analyzed. Liver function was assessed according to the Child-Pugh classification criteria (Grade A, B and C). The pathological grade of hepatocellular carcinoma was divided according to Edmondson-Steiner pathology (Grade 1, 2, 3 and 4). The cancer stage of HCC was obtained at the time of diagnosis based on the Barcelona Clinic Liver Cancer classification (stage 0, 1, 2, 3 and 4). Patients were further divided into different groups based on age:<50 years, 50-59 years, 60-69 years and ≥70 years. The multivariate linear regression, multivariate logistic regression and covariance analysis were applied to investigate the relationship of type 2 diabetes with AFP in HCC. Results Compared to non-diabetic group, the diabetic group had higher negative rate of AFP [54.51%(127/233) vs 37.82%(104/275),χ^2=14.17, P<0.001] and worse liver function (χ^2=9.60, P=0.012). Serum AFP level in type 2 diabetics was remarkably lower than that in non-diabetics [11 (4-249) vs 89 (8-1132) μg/L, Z=-4.32, P<0.001]. After adjustment for age, the AFP level in type 2 diabetics was still significantly lower than that in non-diabetics (H=10.15, P=0.002). Type 2 diabetes was significantly correlated with increased incidence risk of high-grade (grade 3 and 4) HCC (OR=1.80, 95%CI 1.08-3.00, P=0.025). In the HCC patients, the serum level of AFP was negatively correlated with age and T2DM (β=-0.151, P=0.001;β=-0.162, P=0.003). Conclusion Type 2 diabetes mellitas contributes to lower serum AFP level and worse liver function, which is more likely to delay and interfere with HCC diagnosis, leading to higher malignant degree of HCC.