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Although the association between diabetes mellitus (DM) and pancreatic cancer is well described, temporal patterns of changes in fasting blood glucose (FBG) and body mass index (BMI) before pancreatic cancer diagnosis are not known.We reviewed the medical records of pancreatic cancer cases seen at the Mayo Clinic from 15 January 1981 through to 9 July 2004 and selected those residing within 120 miles of Rochester, MN and who were seen at the Mayo Clinic within 30 days of the date of cancer diagnosis (index date). We identified approximately two matched controls per case residing locally and seen at Mayo in the year of their case index date. For the 736 cases and 1,875 controls with at least one outpatient FBG measurement, we abstracted all FBG values, and corresponding heights and weights up to 60 months before the index date and grouped them into 12-month intervals preceding the index. We compared FBG and BMI in each interval between cases and controls.Mean FBG values were similar between cases, compared with controls, in the intervals from months −60 to −48 (102 mg per 100 ml vs. 100 mg per 100 ml,P=0.34) and from months −48 to −36 (106 mg per 100 ml vs. 102 mg per 100 ml,P=0.09), but progressively increased in the intervals from months −36 to −24 (105 mg per 100 ml vs. 100 mg per 100 ml,P=0.01), from months −24 to −12 (114 mg per 100 ml vs. 102 mg per 100 ml,P=0.001), and from months −12 to +1 (123 mg per 100 ml vs. 102 mg per 100 ml,P<0.0001). Though mean BMI values were generally similar in cases and controls up to 12 months before index, they were significantly lower in cases vs. controls in the interval from months −12 to +1 (P< 0.001).Pancreatic cancer is characterized by progressive hyperglycemia beginning up to 24 months before cancer diagnosis in the setting of decreasing BMI. Pancreatic cancer can potentially be diagnosed early if biomarkers are identified that can distinguish pancreatic cancer-induced DM from type II DM.