中国全科医学 ›› 2023, Vol. 26 ›› Issue (26): 3238-3245.DOI: 10.12114/j.issn.1007-9572.2023.0079

所属专题: 内分泌代谢性疾病最新文章合集 肿瘤最新文章合集

• 论著·慢病专项研究·2型糖尿病 • 上一篇    下一篇

2型糖尿病的恶性肿瘤风险:一项基于人群的前瞻性研究

陈伦文, 周阳, 闫国栋, 沈怡, 孙晨, 蔡婉丽, 褚敏捷, 肖静*()   

  1. 226019 江苏省南通市,南通大学公共卫生学院
  • 收稿日期:2022-12-07 修回日期:2023-03-20 出版日期:2023-09-15 发布日期:2023-03-30
  • 通讯作者: 肖静

  • 作者贡献:陈伦文、肖静提出主要研究目标,负责研究的构思与设计,撰写论文;闫国栋、沈怡、孙晨、蔡婉丽进行数据的收集与整理;陈伦文、周阳、闫国栋进行数据清洗和统计学处理;褚敏捷、肖静进行论文的修订;肖静负责文章的质量控制与审查,对文章整体负责,监督管理。
  • 基金资助:
    国家自然科学基金资助项目(82273715)

Risk of Malignant Tumor in Patients with Type 2 Diabetes: a Prospective Population-based Study

CHEN Lunwen, ZHOU Yang, YAN Guodong, SHEN Yi, SUN Chen, CAI Wanli, CHU Minjie, XIAO Jing*()   

  1. School of Public Health, Nantong University, Nantong 226019, China
  • Received:2022-12-07 Revised:2023-03-20 Published:2023-09-15 Online:2023-03-30
  • Contact: XIAO Jing

摘要: 背景 近年来,随着人口老龄化和生活方式的改变,2型糖尿病(T2DM)患者恶性肿瘤高发,且T2DM病程和糖尿病治疗药物的使用可能加速恶性肿瘤的发生。目的 分析T2DM患者恶性肿瘤的发生风险及影响因素。方法 前瞻性纳入2011年10月—2020年12月在南通大学附属医院首次治疗或确诊的T2DM患者,随访截止日期为2021-09-30。通过身份证信息与南通市肿瘤登记系统和死因登记系统联动匹配,获得患者的肿瘤发生与全死因信息。按性别分别计算T2DM患者中恶性肿瘤粗发病率(CIR)和标准化发病比(SIR)。采用Cox比例风险回归分析探讨T2DM病程和药物的使用对T2DM患者发生恶性肿瘤的影响。结果 本研究共纳入T2DM患者12 006例,其中男6 328例(52.71%)、女5 678例(47.29%);经过56 371人年的观察(男性29 543人年,女性26 824人年),共观察到合并恶性肿瘤组601例和单纯T2DM组11 405例。T2DM患者恶性肿瘤CIR:男性1 093.24/10万,女性1 032.51/10万。T2DM患者并发各类癌症的前5顺位,男性依次为结直肠癌、肺癌、肝癌、胃癌、前列腺癌;女性依次为乳腺癌、肺癌、结直肠癌、胃癌、胰腺癌。男性T2DM患者结直肠癌(SIR=2.03)、前列腺癌(SIR=2.24)、胰腺癌(SIR=1.75)、肾癌(SIR=4.25)、甲状腺癌(SIR=3.50)的发生率高于一般人群,而肺癌(SIR=0.61)、食道癌(SIR=0.22)的发生率低于一般人群;女性T2DM患者乳腺癌(SIR=2.59)、结直肠癌(SIR=1.57)、胰腺癌(SIR=2.10)、子宫内膜癌(SIR=2.83)、肾癌(SIR=3.67)、甲状腺癌(SIR=4.00)的发生率高于一般人群,而食道癌(SIR=0.27)的发生率低于一般人群。与T2DM病程1~<3年的患者相比,男性T2DM病程<1年、5~<10年、≥10年分别增加91%〔HR=1.91,95%CI(1.15,3.20)〕、123%〔HR=2.23,95%CI(1.37,3.64)〕和71%〔HR=1.71,95%CI(1.04,2.80)〕的恶性肿瘤发生风险(P<0.05);女性T2DM病程5~<10年、≥10年分别增加79%〔HR=1.79,95%CI(1.10,2.92)〕、99%〔HR=1.99,95%CI(1.24,3.19)〕的恶性肿瘤发生风险(P<0.05)。单独使用胰岛素能分别增加男、女性72%〔HR=1.72,95%CI(1.25,2.36)〕和116%〔HR=2.16,95%CI(1.53,3.05)〕的T2DM患者恶性肿瘤发生风险(P<0.05),且男性单用胰岛素与T2DM病程存在交互作用,随着病程的逐年增加,使男性T2DM患者发生恶性肿瘤的风险平均减缓6%〔HR=0.94,95%CI(0.90,0.98)〕(P交互=0.006)。结论 除食道癌和男性肺癌外,T2DM患者结直肠癌、前列腺癌、胰腺癌、肾癌、甲状腺癌、乳腺癌、子宫内膜癌的发生风险增加57%~325%,且与T2DM病程和使用胰岛素有关,男性T2DM病程5~<10年,女性T2DM病程≥10年的患者发生恶性肿瘤的风险较大,但胰岛素的使用和T2DM病程的增加对T2DM患者并发恶性肿瘤有拮抗的交互作用。

关键词: 癌, 队列研究, 糖尿病, 2型, Cox比例风险回归, 2型糖尿病病程

Abstract:

Background

In recent years, with the aging of the population and the change of lifestyles, patients with type 2 diabetes mellitus (T2DM) have a high prevalence of malignancies, the duration of T2DM and the use of T2DM drugs may accelerate the occurrence of malignant tumor.

Objective

To analyze the risk of incidence and influencing factors of malignant tumors in patients with T2DM.

Methods

Patients with T2DM who were first treated or diagnosed at the Affiliated Hospital of Nantong University from October, 2011 to December, 2020 were prospectively included, with the follow-up termination date of September 30, 2021. The information of tumor incidence and full cause of death of patients were obtained by matching the ID information with the linkage records of the chronic disease tumor registration system and the cause of death registration system of Nantong City. The crudeincidence rate (CIR) and standardized incidence ratio (SIR) of malignant tumors among T2DM patients were calculated separately by gender. Cox proportional hazard regression model was used to explore the effects of the duration of T2DM and drug use on the incidence of malignant tumor in T2DM patients.

Results

A total of 12 006 patients with T2DM were included in this study, involving 6 328 males (52.71%) and 5 678 females (47.29%). After 56 371 person-years of observation (29 543 person-years for males and 26 824 person-years for females), 601 patients with malignant tumor and 11 405 patients with T2DM alone were observed. The CIR of malignant tumor in T2DM patients was 1 093.24/100 000 in men and 1 032.51/100 000 in women, respectively. The top five combined tumors in T2DM patients are colorectal cancer, lung cancer, liver cancer, gastric cancer, and prostate cancer in male, while breast cancer, lung cancer, colorectal cancer, gastric cancer and pancreatic cancer in female. The incidences of colorectal cancer (SIR=2.03), prostate cancer (SIR=2.24), pancreatic cancer (SIR=1.75), kidney cancer (SIR=4.25), thyroid cancer (SIR=3.50) were higher in male T2DM patients than general population, while the incidences of lung cancer (SIR=0.61) and esophageal cancer (SIR=0.22) were lower than general population. The incidences of breast cancer (SIR=2.59), colorectal cancer (SIR=1.57), pancreatic cancer (SIR=2.10), endometrial cancer (SIR=2.83), kidney cancer (SIR=3.67), thyroid cancer (SIR=4.00) were higher in female T2DM patients than general population, while the incidence of esophageal cancer (SIR=0.27) was lower than general population. Compared with T2DM patients with disease duration of 1 to <3 years, the risk of malignant tumor was increased by 91% 〔HR=1.91, 95%CI (1.15, 3.20) 〕, 123%〔HR=2.23, 95%CI (1.37, 3.64) 〕 and 71%〔HR=1.71, 95%CI (1.04, 2.80) 〕in male with disease duration <1 year, 5 to <10 years and≥10 years, respectively, the risk of malignant tumor was increased by 79%〔HR=1.79, 95%CI (1.10, 2.92) 〕 and 99%〔HR=1.99, 95%CI (1.24, 3.19) 〕 in female with T2DM duration of 5 to <10 years and ≥10 years, respectively (P<0.05). Insulin use alone increased the risk of malignant tumor by 72%〔HR=1.72, 95%CI (1.25, 2.36) 〕and 116%〔HR=2.16, 95%CI (1.53, 3.05) 〕 in male and female, respectively (P<0.05). In addition, there was a significant interaction between insulin use and the duration of T2DM in male, the risk of malignant tumor was decreased by an average of 6% with the interaction over the years (Pinteraction=0.006) .

Conclusion

In addition to esophageal cancer in both sexes and lung cancer in male, the risk of colorectal cancer, prostate cancer, pancreatic cancer, kidney cancer, thyroid cancer, breast cancer and endometrial cancer increase by 57%-325% in patients with T2DM, and associated with the disease duration and insulin use, with the greatest risk of malignant tumor in male with disease duration of 5 to <10 years and in female with disease duration of ≥10 years. However, there is an antagonistic interaction between insulin use and increased duration of T2DM disease on the incidence of malignant tumor.

Key words: Carcinoma, Cohort studies, Diabetes mellitus, type 2, Cox proportional hazard regression, Duration of T2DM