Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of Health, Beijing 100029, China.
World J Gastroenterol. 2013 Apr 21;19(15):2395-403. doi: 10.3748/wjg.v19.i15.2395.
To determine the association of diabetes mellitus (DM) and international normalized ratio (INR) level in hepatocellular carcinoma (HCC) patients.
Our present study included 375 HCC patients who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to April 2012, and with a hospital discharge diagnosis of HCC. The demographic, clinical, laboratory, metabolic and instrumental features were analyzed. χ² test, Student's t test and Mann-Whitney U test were used to compare the differences between HCC patients with and without DM. Unconditional multivariable logistic regression analysis was used to determine the association of DM and INR level in HCC patients. A sub-group analysis was performed to assess the effect of liver cirrhosis or hepatitis B virus (HBV) infection on the results. The Pearson correlation test was used to determine the relationship between INR level and fasting glucose. In addition, association between diabetes duration, and diabetes treatment and INR level was determined considering the potentially different effects.
Of the total, 63 (16.8%) patients were diabetic (diabetic group) and 312 (83.2%) patients were diagnosed without diabetes (non-diabetic group). Their mean age was 56.4 ± 11.0 years and 312 (83.2%) patients were male. Compared with patients without DM, the HCC patients with diabetes were older (59.5 ± 10.3 vs 55.8 ± 11.1, P = 0.015), had a lower incidence of HBV infection (79.4% vs 89.1%, P = 0.033), had increased levels of systolic blood pressure (SBP) (133 ± 17 vs 129 ± 16 mmHg, P = 0.048) and INR (1.31 ± 0.44 vs 1.18 ± 0.21, P = 0.001), had lower values of hemoglobin (124.4 ± 23.9 vs 134.2 ± 23.4, P = 0.003) and had a platelet count (median/interquartile-range: 113/64-157 vs 139/89-192, P = 0.020). There was no statistically significant difference in the percentages of males, overweight or obesity, drinking, smoking, cirrhosis and Child classification. After controlling for the confounding effects of age, systolic blood pressure, hemoglobin, platelet count and HBV infection by logistic analyses, INR was shown as an independent variable [odds ratio (OR) = 3.650; 95%CI: 1.372-9.714, P = 0.010]. Considering the effect of liver cirrhosis on results, a sub-group analysis was performed and the study population was restricted to those patients with cirrhosis. Univariate analysis showed that diabetic patients had a higher INR than non-diabetic patients (1.43 ± 0.51 vs 1.25 ± 0.23, P = 0.041). After controlling for confounding effect of age, SBP, hemoglobin, platelet count and HBV infection by logistic analyses, INR level remained as the sole independent variable (OR = 5.161; 95%CI: 1.618-16.455, P = 0.006). No significant difference in the relationship between INR level and fasting glucose was shown by Pearson test (r = 0.070, P = 0.184). Among the 63 diabetic patients, 35 (55.6%) patients had been diagnosed with DM for more than 5 years, 23 (36.5%) received oral anti-diabetic regimens, 11 (17.5%) received insulin, and 30 (47.6%) reported relying on diet alone to control serum glucose levels. No significant differences were found for the association between DM duration/treatment and INR level, except for the age at diabetes diagnosis.
The INR level was increased in HCC patients with DM and these patients should be monitored for the coagulation function in clinical practice.
确定糖尿病（DM）和国际标准化比值（INR）水平与肝细胞癌（HCC）患者的相关性。
本研究纳入了 2003 年 1 月至 2012 年 4 月期间在中国卫生部中日友好医院（北京）接受治疗并经医院诊断为 HCC 的 375 例 HCC 患者。分析了患者的人口统计学、临床、实验室、代谢和仪器特征。采用卡方检验、学生 t 检验和曼-惠特尼 U 检验比较了 DM 患者与非 DM 患者的差异。采用非条件多变量逻辑回归分析确定 DM 与 HCC 患者 INR 水平的相关性。进行了亚组分析，以评估肝硬化或乙型肝炎病毒（HBV）感染对结果的影响。采用 Pearson 相关检验确定 INR 水平与空腹血糖之间的关系。此外，考虑到糖尿病病程和糖尿病治疗可能对 INR 水平产生不同的影响，对其进行了关联分析。
其中 63 例（16.8%）患者为糖尿病患者（糖尿病组），312 例（83.2%）患者未诊断为糖尿病（非糖尿病组）。他们的平均年龄为 56.4±11.0 岁，312 例（83.2%）为男性。与无 DM 患者相比，糖尿病 HCC 患者年龄更大（59.5±10.3 岁比 55.8±11.1 岁，P=0.015），HBV 感染发生率较低（79.4%比 89.1%，P=0.033），收缩压（SBP）较高（133±17mmHg 比 129±16mmHg，P=0.048），INR 较高（1.31±0.44 比 1.18±0.21，P=0.001），血红蛋白（Hb）较低（124.4±23.9g/dL 比 134.2±23.4g/dL，P=0.003），血小板计数较低（中位数/四分位距：113/64-157×10^9/L 比 139/89-192×10^9/L，P=0.020）。两组间男性、超重或肥胖、饮酒、吸烟、肝硬化和 Child 分级的比例无统计学差异。通过逻辑分析控制年龄、SBP、Hb、血小板计数和 HBV 感染的混杂效应后，INR 为独立变量[比值比（OR）=3.650；95%可信区间（CI）：1.372-9.714，P=0.010]。考虑到肝硬化对结果的影响，进行了亚组分析，将研究人群限制为肝硬化患者。单因素分析显示，糖尿病患者的 INR 高于非糖尿病患者（1.43±0.51 比 1.25±0.23，P=0.041）。通过逻辑分析控制年龄、SBP、Hb、血小板计数和 HBV 感染的混杂效应后，INR 水平仍然是唯一的独立变量（OR=5.161；95%CI：1.618-16.455，P=0.006）。Pearson 检验未显示 INR 水平与空腹血糖之间存在显著相关性（r=0.070，P=0.184）。在 63 例糖尿病患者中，35 例（55.6%）患者的糖尿病诊断时间超过 5 年，23 例（36.5%）接受口服抗糖尿病药物治疗，11 例（17.5%）接受胰岛素治疗，30 例（47.6%）报告仅依靠饮食控制血糖水平。除糖尿病诊断年龄外，DM 病程/治疗与 INR 水平之间无显著相关性。
DM 患者的 INR 水平升高，临床实践中应监测这些患者的凝血功能。
