Utility of hemoglobin A1c and blood glucose monitoring for early detection of pancreatic cancer in a high-risk cohort.

Abstract

e16466 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis largely due to late-stage diagnosis, even among high-risk individuals under surveillance with MRI/MRCP and/or EUS. However current surveillance methods can be invasive, costly, and are imperfect in their ability to detect PDAC early. PDAC can be associated with early metabolic changes, including hyperglycemia and diabetes, and therefore changes in HgbA1c and glucose have been hypothesized to potentially serve as a non-invasive adjunctive measure for PDAC early detection in high-risk populations. Inspired by the Meziani et al study of HgbA1c and glucose trends in a Dutch cohort of high-risk individuals, the aim of this study is to examine HgbA1c and glucose trends in a more heterogenous population with a broader genetic profile and risk factors, greater racial diversity, and longer mean length of follow-up. Methods: Retrospective analysis of high-risk individuals undergoing PDAC surveillance who were enrolled in the CAPS5 study at a single study center between 1/1/2015 and 12/31/2025 (mean follow-up of 56 months). Those included in the analysis had at least one measured glucose and HgbA1c level, without a prior history of diabetes. Individuals were separated into cohorts of those who developed PDAC during the surveillance period and those who did not. Percent change in glucose and HgbA1c was assessed in each cohort from first visit under surveillance to date of last follow up. Results: Of the 268 included individuals, 6 (2.2%) developed PDAC during the surveillance period. Two (33%) developed diabetes in the PDAC cohort and 15 (5.72%) developed diabetes in the surveillance cohort who did not develop PDAC. The mean values of glucose (109.5 in non-PDAC vs 123.2 in PDAC, p = 0.015) and HgbA1c (5.8 in non-PDAC vs 6.2 in PDAC, p = 0.019) did differ significantly between cohorts. However, neither glucose trends nor HgbA1c trends differed significantly between the control and PDAC cohorts. Conclusions: In this study, measures of glucose and HgbA1c did not meaningfully contribute to the early detection of PDAC, nor provide a clear pre-diagnostic signal in a high-risk cohort. However, the sample size of this study is small, and larger prospective studies of glucose/HgbA1c monitoring need to be performed to confirm these results. Overall, this data highlights the potential limitations of glycemic monitoring as a non-invasive blood- based tool for early PDAC detection, and emphasizes the ongoing need for more sensitive biomarkers as an adjunct to imaging surveillance strategies. Changes in Glucose and A1c from initial visit to last follow-up. Non-PDAC (n=262) PDAC (n =6) p-value Glucose Range of change (%) 3.81% 7.29% 0.67 Mean (SD) 2.20 (21.96) 4.83 (22.76) 0.79 HbA1c Range of change (%) 1.86% 1.82% 0.98 Mean (SD) 0.09 (0.36) 0.12 (0.27) 0.75