Erica Dugnani1, Alessandra Gandolfi1, Gianpaolo Balzano2, Marina Scavini1, Valentina Pasquale1, Francesca Aleotti2, Daniela Liberati1, Gaetano Di Terlizzi3, Giovanna Petrella3, Michele Reni3, Claudio Doglioni4, Emanuele Bosi5, Massimo Falconi6, Lorenzo Piemonti7. 1. Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. 2. Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. 3. Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. 4. Department of Pathology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. 5. Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. 6. Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. 7. Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. Electronic address: piemonti.lorenzo@hsr.it.
Abstract
BACKGROUND: Identification of a specific diabetes signature associated to pancreatic ductal carcinoma (PDAC) could be a key to detect asymptomatic, early stage tumors. We aim to characterize the clinical signature and the pathogenetic factors of the different types of diabetes associated with PDAC, based on the time between diabetes and cancer diagnosis. METHODS: Prospective observational study on 364 PDAC patients admitted to a referral center for pancreatic disease. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. RESULTS: The prevalence of diabetes in patients was 67%. Considering 174 patients (47.8%) already having diabetes when diagnosed with PDAC (long duration, short duration, concomitant), the clinical and biochemical profile was similar to that of patients with type 2 diabetes (T2D). Diabetes was associated with known risk factors (i.e., age, sex, family history for diabetes and increased BMI) and both beta-cell dysfunction and insulin resistance were present. Considering 70 patients (19.2%) with onset of diabetes after PDAC diagnosis (early and late onset), the strongest predictor was the loss of beta-cell mass following pancreatectomy in patients with risk factors for T2D. CONCLUSION: Different types of diabetes according to the time between diabetes and PDAC diagnosis are clinical entities widely overlapping with T2D. Therefore, the success of a strategy considering diabetes onset as a marker of asymptomatic PDAC will largely depend on our ability to identify new diabetes-unrelated biomarkers of PDAC.
BACKGROUND: Identification of a specific diabetes signature associated to pancreatic ductal carcinoma (PDAC) could be a key to detect asymptomatic, early stage tumors. We aim to characterize the clinical signature and the pathogenetic factors of the different types of diabetes associated with PDAC, based on the time between diabetes and cancer diagnosis. METHODS: Prospective observational study on 364 PDAC patients admitted to a referral center for pancreatic disease. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. RESULTS: The prevalence of diabetes in patients was 67%. Considering 174 patients (47.8%) already having diabetes when diagnosed with PDAC (long duration, short duration, concomitant), the clinical and biochemical profile was similar to that of patients with type 2 diabetes (T2D). Diabetes was associated with known risk factors (i.e., age, sex, family history for diabetes and increased BMI) and both beta-cell dysfunction and insulin resistance were present. Considering 70 patients (19.2%) with onset of diabetes after PDAC diagnosis (early and late onset), the strongest predictor was the loss of beta-cell mass following pancreatectomy in patients with risk factors for T2D. CONCLUSION: Different types of diabetes according to the time between diabetes and PDAC diagnosis are clinical entities widely overlapping with T2D. Therefore, the success of a strategy considering diabetes onset as a marker of asymptomatic PDAC will largely depend on our ability to identify new diabetes-unrelated biomarkers of PDAC.