Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes

      Background & Aims

      Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD.


      We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD.


      In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC.


      Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.

      Graphical abstract


      Abbreviations used in this paper:

      BG (blood glucose), EAG (estimated average glucose), END-PAC (Enriching New-Onset Diabetes for Pancreatic Cancer), EXPAND (Examination of the Pancreas in New-Onset Diabetes), FBG (fasting blood glucose), NOD (new-onset diabetes), PC (pancreatic cancer), PC-NOD (pancreatic cancer in new-onset diabetes), REP (Rochester Epidemiology Project), T2-NOD (type 2 new-onset diabetes)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rahib L.
        • Smith B.D.
        • Aizenberg R.
        • et al.
        Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.
        Cancer Res. 2014; 74: 2913-2921
        • Chari S.T.
        • Leibson C.L.
        • Rabe K.G.
        • et al.
        Probability of pancreatic cancer following diabetes: a population-based study.
        Gastroenterology. 2005; 129: 504-511
      1. SEER. Fast facts: pancreatic cancer. Available at: Accessed January 17, 2018.

        • Chari S.T.
        Detecting early pancreatic cancer: problems and prospects.
        Semin Oncol. 2007; 34: 284-294
        • Ogawa Y.
        • Tanaka M.
        • Inoue K.
        • et al.
        A prospective pancreatographic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus.
        Cancer. 2002; 94: 2344-2349
        • Damiano J.
        • Bordier L.
        • Le Berre J.P.
        • et al.
        Should pancreas imaging be recommended in patients over 50 years when diabetes is discovered because of acute symptoms?.
        Diabetes Metab. 2004; 30: 203-207
        • Illes D.
        • Terzin V.
        • Holzinger G.
        • et al.
        New-onset type 2 diabetes mellitus—a high-risk group suitable for the screening of pancreatic cancer?.
        Pancreatology. 2016; 16: 266-271
        • Munigala S.
        • Singh A.
        • Gelrud A.
        • et al.
        Predictors for pancreatic cancer diagnosis following new-onset diabetes mellitus.
        Clin Transl Gastroenterol. 2015; 6: e118
        • Boursi B.
        • Finkelman B.
        • Giantonio B.J.
        • et al.
        A clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes.
        Gastroenterology. 2017; 152: 840-850.e3
        • Gupta S.
        • Vittinghoff E.
        • Bertenthal D.
        • et al.
        New-onset diabetes and pancreatic cancer.
        Clin Gastroenterol Hepatol. 2006; 4: 1366-1372
        • Aggarwal G.
        • Rabe K.G.
        • Petersen G.M.
        • et al.
        New-onset diabetes in pancreatic cancer: a study in the primary care setting.
        Pancreatology. 2012; 12: 156-161
        • Fraser L.A.
        • Twombly J.
        • Zhu M.
        • et al.
        Delay in diagnosis of diabetes is not the patient’s fault.
        Diabetes Care. 2010; 33: e10
        • Harris M.I.
        • Klein R.
        • Welborn T.A.
        • et al.
        Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis.
        Diabetes Care. 1992; 15: 815-819
        • Porta M.
        • Curletto G.
        • Cipullo D.
        • et al.
        Estimating the delay between onset and diagnosis of type 2 diabetes from the time course of retinopathy prevalence.
        Diabetes Care. 2014; 37: 1668-1674
        • Ford E.S.
        • Williamson D.F.
        • Liu S.
        Weight change and diabetes incidence: findings from a national cohort of US adults.
        Am J Epidemiol. 1997; 146: 214-222
        • Sah R.P.
        • Nagpal S.J.S.
        • Mukhopadhyay D.
        • et al.
        New insights into pancreatic cancer-induced paraneoplastic diabetes.
        Nat Rev Gastroenterol Hepatol. 2013; 10: 423-433
        • Hart P.A.
        • Kamada P.
        • Rabe K.G.
        • et al.
        Weight loss precedes cancer-specific symptoms in pancreatic cancer-associated diabetes mellitus.
        Pancreas. 2011; 40: 768-772
        • DeJesus R.S.
        • Breitkopf C.R.
        • Rutten L.J.
        • et al.
        Incidence rate of prediabetes progression to diabetes: modeling an optimum target group for intervention.
        Popul Health Manag. 2017; 20: 216-223
        • Nichols G.A.
        • Hillier T.A.
        • Brown J.B.
        Normal fasting plasma glucose and risk of type 2 diabetes diagnosis.
        Am J Med. 2008; 121: 519-524
        • Pannala R.
        • Leirness J.B.
        • Bamlet W.R.
        • et al.
        Prevalence and clinical profile of pancreatic cancer–associated diabetes mellitus.
        Gastroenterology. 2008; 134: 981-987
      2. Centers for Disease Control and Prevention. Available at: Accessed January 17, 2018.

      3. American Cancer Society. Pancreatic cancer risk factors. Available at: Accessed January 17, 2018.

        • Melton III, L.J.
        History of the Rochester Epidemiology Project.
        Mayo Clin Proc. 1996; 71: 266-274
        • Rocca W.A.
        • Yawn B.P.
        • Sauver J.L.S.
        • et al.
        History of the Rochester Epidemiology Project: half a century of medical records linkage in a US population.
        Mayo Clin Proc. 2012; 87: 1202-1213
        • Chari S.T.
        • Klee G.G.
        • Miller L.J.
        • et al.
        Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.
        Gastroenterology. 2001; 121: 640-645
        • Aggarwal G.
        • Ramachandran V.
        • Javeed N.
        • et al.
        Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice.
        Gastroenterology. 2012; 143: 1510-1517.e1
        • Pannala R.
        • Leibson C.L.
        • Rabe K.G.
        • et al.
        Temporal association of changes in fasting blood glucose and body mass index with diagnosis of pancreatic cancer.
        Am J Gastroenterol. 2009; 104: 2318
        • Chari S.T.
        • Leibson C.L.
        • Rabe K.G.
        • et al.
        Pancreatic cancer–associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer.
        Gastroenterology. 2008; 134: 95-101
        • Cohen J.D.
        • Li L.
        • Wang Y.
        • et al.
        Detection and localization of surgically resectable cancers with a multi-analyte blood test.
        Science. 2018; 359: 926-930
        • Pepe M.S.
        • Feng Z.
        • Huang Y.
        • et al.
        Integrating the predictiveness of a marker with its performance as a classifier.
        Am J Epidemiol. 2008; 167: 362-368
        • Pepe M.S.
        • Janes H.
        • Li C.I.
        • et al.
        Early-phase studies of biomarkers: what target sensitivity and specificity values might confer clinical utility?.
        Clin Chem. 2016; 62: 737-742
        • Sharma A.
        • Smyrk T.C.
        • Levy M.J.
        • et al.
        Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer before diagnosis.
        Gastroenterology. 2018; 155: 490-500
        • Pelaez-Luna M.
        • Takahashi N.
        • Fletcher J.G.
        • et al.
        Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis.
        Am J Gastroenterol. 2007; 102: 2157-2163
        • Bruenderman E.
        • Martin II, R.C.
        A cost analysis of a pancreatic cancer screening protocol in high-risk populations.
        Am J Surg. 2015; 210: 409-416

      Linked Article