Association between age at diabetes onset or diabetes duration and subsequent risk of pancreatic cancer: Results from a longitudinal cohort and mendelian randomization study

Baiyong Shen; Yanyun Li; Chang-Sheng Sheng; Lili Liu; Tianzhichao Hou; Nan Xia; Siming Sun; Ya Miao; Yi Pang; Kai Gu; Xiongxiong Lu; Chenlei Wen; Yi Cheng; Yulin Yang; Dan Wang; Yijie Zhu; Minna Cheng; Katie Harris; Zachary T Bloomgarden; Jingyan Tian; John Chalmers; Yan Shi

doi:10.1016/j.lanwpc.2022.100596

Association between age at diabetes onset or diabetes duration and subsequent risk of pancreatic cancer: Results from a longitudinal cohort and mendelian randomization study

Lancet Reg Health West Pac. 2022 Sep 17:30:100596. doi: 10.1016/j.lanwpc.2022.100596. eCollection 2023 Jan.

Authors

Baiyong Shen^{1

2

3

4}, Yanyun Li⁵, Chang-Sheng Sheng⁶, Lili Liu⁵, Tianzhichao Hou⁷, Nan Xia⁷, Siming Sun⁸, Ya Miao⁷, Yi Pang⁵, Kai Gu⁵, Xiongxiong Lu^{1

2

3

4}, Chenlei Wen^{1

2

3

4}, Yi Cheng⁶, Yulin Yang⁷, Dan Wang⁶, Yijie Zhu⁷, Minna Cheng⁵, Katie Harris⁹, Zachary T Bloomgarden¹⁰, Jingyan Tian⁷, John Chalmers⁹, Yan Shi^{5

11}

Affiliations

¹ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
⁴ Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Division of Chronic Non-Communicable Disease and Injury, Shanghai municipal center for disease control and prevention, Shanghai, 200336, China.
⁶ Department of Cardiovascular Medicine, Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluation, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁷ State Key Laboratory of Medical Genomics, Clinical Trial Center, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.
⁸ Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
⁹ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
¹⁰ Department of Medicine, Division of Endocrinology, Diabetes, and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
¹¹ Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China.

Abstract

Background: The aim of the study is to estimate the incidence of pancreatic cancer among individuals with new-onset type 2 Diabetes (T2DM) and evaluate the relationship of pancreatic cancer risk with age at diabetes onset and diabetes duration.

Methods: This longitudinal cohort study included 428,362 new-onset T2DM patients in Shanghai and Mendelian randomization (MR) in the east-Asian population were used to investigate the association. Incidence rates of pancreatic cancer in all patients and by subgroups were calculated and compared to the general population.

Findings: A total of 1056 incident pancreatic cancer cases were identified during eight consecutive years of follow-up. The overall pancreatic cancer annual incidence rate was 55·28/100,000 person years in T2DM patients, higher than that in the general population, with a standardized incidence ratio (SIR) of 1·54 (95% confidence interval [CI], 1·45-1·64). The incidence of pancreatic cancer increased with age and a significantly higher incidence was observed in the older groups with T2DM. However, the relative pancreatic cancer risk was inversely related to age of T2DM onset, and a higher SIR of 5·73 (95%CI, 4·49-7·22) was observed in the 20-54 years old group. The risk of pancreatic cancer was elevated at any diabetes duration. Fasting blood glucose ≥10·0 mmol/L was associated with increased risk of pancreatic cancer. MR analysis indicated a positive association between T2DM and pancreatic cancer risk.

Interpretation: Efforts toward early and close follow-up programs, especially in individuals with young-onset T2DM, and the improvement of glucose control might represent effective strategies for improving the detection and results of treatment of pancreatic cancer.

Funding: Chinese National Natural Science Foundation.

Keywords: Diabetes duration; Mendelian randomization; Onset age; Pancreatic cancer; Type 2 diabetes mellitus.