Pancreatic cancer incidence and survival in lean and obese adults with type 2 diabetes: A propensity matched analysis.

Abstract

10576 Background: Type 2 diabetes mellitus (T2DM) and excess adiposity are independent risk factors for pancreatic cancer. Pancreatic cancer risk within T2DM across body-mass index (BMI) strata is heterogeneous in real-world cohorts and lean T2DM individuals may represent a distinct high risk phenotype. We compared pancreatic cancer incidence and post-diagnosis survival across BMI strata. Methods: We performed a retrospective comparative outcomes analysis using the TriNetX network. Adults with T2DM (HbA1c ≥6.5%) were categorized as obese (BMI ≥30 kg/m²) or lean (BMI <25 kg/m²). The lean cohort additionally excluded any patient with prior BMI of >25 kg/m² to control for cancer associated weight loss. The index event was first T2DM diagnosis, and outcomes were evaluated after a 365-day window. Patients with pancreatic cancer prior to the outcome window were excluded. Propensity score matching was done using the following parameters: age, sex, smoking status, pancreatitis, pancreatic cysts, chronic kidney disease, gallstones, family history of pancreatic cancer, and HbA1c. Outcomes assessed were incident pancreatic cancer over 10 years and all-cause mortality among patients with pancreatic cancer and T2DM. Results: Total number of patients in the obese group was 1,759,075 with mean age of 57 ± 13.4 years and in the lean cohort were 205,193 with a mean age of 61.8 ± 16.6 years. After propensity score matching, there were 204,086 patients in each group. Mean HbA1c levels were 7.4 ± 1.8% in the obese group and 7.9 ± 2.2% in the lean BMI group. The incidence of pancreatic cancer was 0.16% (n = 335) in obese patients as compared to 0.23% in lean (n = 478) patients with a risk difference of 0.07% (p <0.001). Obesity was associated with lower pancreatic cancer risk (RR 0.692, 95% CI 0.603–0.797; p < 0.001). In the subgroup analysis of patients diagnosed with pancreatic cancer, obese patients had longer median survival (1,109 vs 651 days) with HR 0.853 (95% CI 0.793 - 0.918; p <0.001). Conclusions: Lean adults with T2DM had a higher incidence of pancreatic cancer and worse post-diagnosis survival than obese patients. These results identify lean T2DM as a distinct high-risk phenotype and demonstrate that pancreatic cancer risk within T2DM is heterogeneous and not solely attributable to excess adiposity. Further investigation is needed to elucidate the biological mechanisms underlying this association and its implications for clinical risk assessment. Pancreatic cancer incidence and associated risk estimates among obese and lean adults with type 2 diabetes mellitus. Cohort Pancreatic cancer incidence RD RR Obese T2DM(n = 204,086) 0.16% (n = 335) 0.07% (95% CI: 0.04 - 0.10), p < 0.001 1.44 (95% CI: 1.25 - 1.66) Lean T2DM(n = 204,086) 0.23% (n = 478) Abbreviations: CI, confidence interval; RD, risk difference; RR, relative risk; T2DM, type 2 diabetes mellitus.