Background: Pancreatic cancer diagnoses are frequently preceded by a new diabetes diagnosis. Screening individuals newly diagnosed with diabetes could enable earlier pancreatic cancer detection. We sought to estimate the risk of pancreatic cancer by age, sex, race and time since diabetes diagnosis. Methods: Johns Hopkins Medicine conducted this de-identified claims-based cohort study using the Optum Labs Data Warehouse (OLDW). Enrollees from 1/2008 to 9/2018 were identified as non-diabetic or newly diagnosed diabetics and time to pancreatic cancer analysis was conducted using a flexible Weibull model. Diabetes and cancer were defined using ICD-9/10 codes. Results: Our risk set included 4,732,313 individuals (424,129 newly diabetic) in 5,844,934 enrollment periods. Individuals with newly diagnosed diabetes were at an increased hazard ratio (HR) of pancreatic cancer but this effect waned over time. The HR of pancreatic cancer following a diabetes diagnosis was higher in younger individuals and varied by race (lower HR in non-White individuals) (p<0.01, main effects and interactions). Thus, the probability of pancreatic cancer following a diabetes diagnosis was dependent on age, race, and sex. For example: the 1-year probability of pancreatic cancer in a white male aged 75 was 0.45% (95%CI 0.41%-0.49%) if they were newly diagnosed with diabetes and 0.090% (95%CI 0.084%-0.096%) fi they were free of diabetes. In contrast, risk was lower if they were age 55 at 0.15% (new-diabetic, 95%CI 0.13%-0.16) and 0.022% (diabetes free, 95%CI 0.020%-0.023%). The HR of pancreatic cancer for individuals with newly diagnosed diabetes compared to those free of diabetes was highest 1 month after diagnosis (HR=9.6 and 14.7 for a 75 and 55 year old while male, respectively) but decreased in the following months, with a ~39% reduction in HR from 1-to-3 months, ~17% from 3 -to-6 months, and ~14% from 6 month-to -1 year (p<0.01). Conclusions: Consideration of the age-race-sex specific probability of pancreatic cancer and time since diabetes diagnosis is necessary to when evaluating the risk of pancreatic cancer following a diabetes diagnosis. Keywords: Pancreatic adenocarcinoma, diabetes, race, risk

Conflict of interest: Material support for the study described in this publication was provided by Optum Labs via the Stand up to cancer relationship. Dr. Klein served as a paid consultant to Optum Labs in 2018. This arrangement was reviewed and approved by the Johns Hopkins University in accordance with its conflicts of interest policies. No other conflicts are declared.

This work was supported by the Stand Up To Cancer Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant (Grant Number: SU2C AACR DT25 17).Stand Up To Cancer is a program of the Entertainment Industry Foundation. SU2C research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Our claims based cohort was defined using de-identified administrative claims data from the Optum Labs Data Warehouse (OLDW). Since this study involved analysis of pre-existing, de-identified data, it was exempt from Institutional Review Board review at Johns Hopkins.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data underlying the results of this study are third party data owned by Optum Labs and contain sensitive patient information; therefore the data is only available upon request. Interested researchers engaged in HIPAA compliant research may contactvconnected@optum.com for data access requests. The data use requires researchers to pay for rights to use and access the data. All interested researchers can access the data in the same manner as the authors - the authors had no special access privileges.