Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Carcinogenesis. 2011 Jun;32(6):876-81. doi: 10.1093/carcin/bgr058. Epub 2011 Apr 3.
This study aimed to investigate the association of fasting insulin and glucose levels with hepatocellular carcinoma (HCC) risk in a case-cohort study within a cohort (1989-2006) of 2903 male government employees chronically infected with hepatitis B virus (HBV) in Taiwan. Insulin, glucose and HBV-related factors were assayed in baseline plasma among 124 HCC cases and a random subcohort of 1084 of the total cohort. After adjustment for demographics and HBV-related factors, including viral load and genotype, the HCC risk was higher for the highest [>6.10 μU/ml, hazard ratio (HR) = 2.36, 95% confidence interval (CI): 1.43-3.90] and lowest (<2.75 μU/ml, HR = 1.57, 95% CI: 0.96-2.58) categories of insulin, compared with insulin of 2.75-4.10 μU/ml. The dose-response relationship between insulin and HCC varied by follow-up time, with stronger association for the HCC cases that occurred ≥8 years after baseline (P for trend <0.0001). The effect of higher insulin on HCC risk remained after adjustment for other metabolic factors, and was fairly consistent across strata of age, body mass index, and HBV genotypic variants. However, it was more profound among those with viral load <4.39 log(10) copies/ml at recruitment (>6.10 μU/ml, HR = 6.15, 95% CI: 2.48-15.22). Higher insulin was also associated with an increased risk for cirrhosis diagnosed by ultrasonography and elevated alanine aminotransferase. No association with either cirrhosis or HCC was noted for glucose or diabetes after adjusting for insulin. In conclusion, elevated insulin levels are an independent risk factor for HCC among HBV carriers, especially for those with lower viral load.
本研究旨在探讨空腹胰岛素和血糖水平与台湾乙型肝炎病毒（HBV）慢性感染者队列（1989-2006 年）内病例对照研究中肝细胞癌（HCC）风险之间的关系。在 124 例 HCC 病例和总队列中随机抽取的 1084 例的基线血浆中测定了胰岛素、血糖和 HBV 相关因素。在校正了人口统计学和 HBV 相关因素，包括病毒载量和基因型后，最高 [>6.10 μU/ml，风险比（HR）=2.36，95%置信区间（CI）：1.43-3.90] 和最低 [<2.75 μU/ml，HR = 1.57，95% CI：0.96-2.58] 胰岛素类别与 HCC 风险更高，与 2.75-4.10 μU/ml 胰岛素相比。胰岛素与 HCC 之间的剂量-反应关系随随访时间而变化，在基线后≥8 年发生的 HCC 病例中相关性更强（P 趋势<0.0001）。在调整了其他代谢因素后，较高的胰岛素对 HCC 风险的影响仍然存在，并且在年龄、体重指数和 HBV 基因型变异的各个亚组中相当一致。然而，在招募时病毒载量<4.39 log(10) 拷贝/ml 的人群中（>6.10 μU/ml，HR = 6.15，95% CI：2.48-15.22），这种影响更为明显。较高的胰岛素水平也与超声诊断的肝硬化和丙氨酸氨基转移酶升高的风险增加有关。在校正胰岛素后，血糖或糖尿病与肝硬化或 HCC 均无关联。总之，在 HBV 携带者中，升高的胰岛素水平是 HCC 的独立危险因素，尤其是在病毒载量较低的人群中。
