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To characterize the clinical signature and etiopathogenetic factors of diabetes associated with pancreas disease [type 3 diabetes mellitus (T3cDM)]. To estimate incidence and identify predictors of both diabetes onset and remission after pancreatic surgery. A prospective observational study was conducted. From January 2008 to December 2012, patients (n = 651) with new diagnosis of pancreatic disease admitted to the Pancreatic Surgery Unit of the San Raffaele Scientific Institute were evaluated. 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. At baseline, the prevalence of diabetes was 38 % (age of onset 64 ± 11 years). In most cases, diabetes occurred within 48 months from pancreatic disease diagnosis. Among different pancreatic diseases, minor differences were observed in diabetes characteristics, with the exception of the prevalence. Diabetes appeared associated with classical risk factors for type 2 diabetes (i.e., age, sex, family history of diabetes and body mass index), and both beta-cell dysfunction and insulin resistance appeared relevant determinants. The prevalence of adult-onset autoimmune diabetes was as previously reported within type 2 diabetes. Within a few days after surgery, either diabetes remission or new-onset diabetes was observed. In patients with pancreatic cancer, no difference in diabetes remission was observed after palliative or resective surgery. Classical risk factors for type 2 diabetes were associated with the onset of diabetes after surgery. T3cDM appeared as a heterogeneous entity strongly overlapped with type 2 diabetes.