Risk Factors of Pancreatic Cancer in Patients With Type 2 Diabetes Mellitus

The Hong Kong Diabetes Study

Raymond Ngai Chiu Chan; Teddy Tai Loy Lee; Oscar Hou In Chou; Jenny So; Cheuk To Chung; Edward Christopher Dee; Kenrick Ng; Pias Tang; Leonardo Roever; Tong Liu; Wing Tak Wong; Gary Tse; Sharen Lee


J Endo Soc. 2022;6(11) 

In This Article

Abstract and Introduction


Context: Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors.

Objective: The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study.

Methods: This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed.

Results: This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01–1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30–2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25–2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35–3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28–12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond.

Conclusion: Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs.


Diabetes mellitus (DM) is a global public health concern currently affecting around 463 million patients worldwide. Current estimates predict a further rise of 51% by 2045.[1] DM has long been associated with a number of microvascular and macrovascular complications. In recent years, more attention has been drawn to the association between DM and various cancers.[2–4] Several meta-analyses were published establishing the relations between DM and many common malignancies including lung cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, breast cancer, as well as cancer mortality.[5–10]

Pancreatic cancer (PaC), a relatively rare yet highly aggressive malignancy, is associated with a dismal prognosis and has a 5-year-survival rate of less than 5%.[11] It is currently the third leading cause of cancer-related death in the United States.[12] Despite advances in oncological treatments over previous decades, it remains a growing source of cancer death, potentially because of difficulty in diagnosis and delayed treatment. Identifying patients at risk of developing PaC and subsequent workups may hence be important to improve the prognosis.

Meanwhile, PaC has been associated with DM.[13–15] In a meta-analysis of 35 cohort studies in 2011, DM was identified as a risk factor of PaC independent of sex, alcohol consumption, body mass index, and smoking.[16] In another meta-analysis conducted in 2015, Song et al[17] pooled data from 44 studies and further reported that a long DM duration was associated with an elevated risk of PaC of up to 64%. In addition, DM predicts not only incident PaC, but also PaC-related mortality. A large-scale cohort study of 1 089 586 individuals in the United States reported an adjusted risk ratio of up to 2.05 for PaC mortality in DM patients compared to those without DM.[18]

However, although DM patients are at higher risks of developing PaC, risk stratification is imperfect as there is limited literature reporting the potential risk factors of PaC in DM patients thus far. Therefore, the present study aims to examine the predictors for PaC in patients with type 2 DM (T2DM) in a territory-wide, retrospective cohort study.