New Onset Diabetes in Pancreatic Adenocarcinoma Does Not Correlate With Molecular Subtype

Background and objectives: Studies show that new onset diabetes mellitus (DM) (NOD) predates the diagnosis of PDAC by up to 2 years. Two tumor-intrinsic molecular subtypes of PDAC that are prognostic and predictive of chemotherapy response have been described and validated. We hypothesize that patients with NOD may have different molecular subtypes and prognoses.

Methods: This is a single-institution study of patients who underwent resection for PDAC from 2009 to 2022 with de-identified samples available for sequencing. Demographic and clinical factors were examined using bivariate and multivariate analysis.

Results: A total of 97 patients met inclusion criteria: 70 with no history of DM, 11 with longstanding DM (> 2 years), and 16 with NOD. The demographics between groups were overall similar. After controlling for age, sex, race, BMI, and tobacco history, NOD was not a significant predictor of PDAC subtype. There were no survival differences between groups. Transcriptomic analysis suggests the upregulation of inflammatory and immune activation and regulation pathways in NOD.

Conclusions: As continued interest in NOD and PDAC mounts, we are the first to examine if NOD may be associated with molecular subtypes and outcomes. Further investigation into the underlying pathophysiology of the NOD group is still needed.