The bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation.
We conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity.
The analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96–2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88–9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27–1.55).
The markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.
- • There is limited data about the association between pancreatic cancer (PC) and diabetes mellitus (DM) of different durations, particularly DM of very short duration (<3 months).
- • We found a marked difference in risk of PC according to duration of DM with extremely high risk for DM of <12 months duration.
- • The associations between PC and DM of duration <3 months and 3 to <6 months were particularly strong; these could not be explained by detection bias.
- • The elevated risk of PC was evident even with DM of 10 or more years.
- • Differentiating high-risk new-onset DM secondary to PC from those with type 2 DM will provide a potential avenue for early detection of PC.
Pancreatic cancer (PC) is the 7th most common cause of cancer mortality globally, and in more developed regions it is predicted to rise from being the 4th to the 2nd most common cause of cancer mortality by 2030. Five-year survival is approximately 10% and median survival is less than 12 months. The poor survival is largely due to the fact that most patients present with locally advanced or metastatic disease and are therefore not suitable for curative surgery. Understanding risk factors for PC may facilitate prevention and early detection.
The association between diabetes mellitus (DM) and PC is well established and it appears that there is a bidirectional association, with long-standing type 2 DM being a risk factor for PC, and new-onset DM (also called type 3c DM) being an early clinical manifestation. Previously published literature has reported an approximately two-fold increased risk of PC in patients with DM of any duration. However, relatively few studies have examined the strength of the relationship with duration of DM, and a number of these have had considerable limitations. For example, some studies captured the presence of DM from hospital data, and people who have been hospitalised are not necessarily representative of the broader population with DM. Small sample sizes and reliance on self-report to ascertain DM and its duration are also limitations of previous studies. In addition, few studies have examined the association between PC and DM of very short duration (e.g., <3 months), with most examining DM less than one year as the shortest time frame . Understanding the risk of PC within a short time frame after diagnosis of DM is of particular relevance with respect to cancer surveillance.
We aimed to investigate the association between DM and risk of PC using a large population-based dataset based on linked administrative data for women, particularly aiming to calculate the risk according to duration of DM.