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 1，2011 to December 31，2020 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 incidence rate 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 personyears 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 incidence of malignant tumor in T2DM patients was 1 093.24/100 000 in men and 1 032.51/100 000 in women，respectively. 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. 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. 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（ P=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%-300% 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