Date: | 2018 Aug |
PMID: | |
Category: | 2 |
Authors: | Ayush Sharma 1, Thomas C Smyrk 2, Michael J Levy 1, Mark A Topazian 1, Suresh T Chari 3 |
Abstract: |
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Background and Aims: It is unclear how long pancreatic ductal adenocarcinomas (PDACs) are present before diagnosis. Patients with PDAC usually develop hyperglycemia and diabetes before the tumor is identified. If early invasive PDACs are associated with hyperglycemia, the duration of hyperglycemia should associate with the time that they have had the tumor.
Methods: We collected data on patients with PDACs from medical databases in Olmsted County, Minnesota, from 2000 through 2015 and from the Mayo Clinic's tumor registry from January 1, 1976, through January 1, 2017. We compared glycemic profiles of patients with PDAC (cases) compared with patients without cancer, matched for age and sex (controls). We analyzed temporal fasting blood glucose (FBG) profiles collected for 60 months before patients received a PDAC diagnosis (index date) (n = 219) (cohort A), FBG profiles of patients with resected PDAC (n = 526) stratified by tumor volume and grade (cohort B), and temporal FBG profiles of patients with resected PDACs from whom long-term FBG data were available (n = 103) (cohort C). The primary outcome was to estimate duration of presence of invasive PDAC before its diagnosis based on hyperglycemia, defined as significantly higher (P < .05) FBG levels in cases compared with controls.
Results: In cohort A, the mean FBG did not differ significantly between cases and controls 36 months before the index date. Hyperglycemia was first noted 36 to 30 months before PDAC diagnosis in all cases, those with or without diabetes at baseline and those with or without resection at diagnosis. FBG level increased until diagnosis of PDAC. In cohort B, the mean FBG did not differ significantly in controls vs cases with PDACs below 1.0 mL. The smallest tumor volume associated with hyperglycemia was 1.1 to 2.0 mL; FBG level increased with tumor volume. FBG varied with tumor grade: well- or moderately differentiated tumors (5.8 mL) produced the same FBG levels as smaller, poorly differentiated tumors (1.5 mL) (P < .001). In cohort C, the duration of prediagnostic hyperglycemia for cases with large-, medium-, or small-volume PDACs was 36 to 24, 24 to 12, and 12 to 0 months, respectively. PDAC resection resolved hyperglycemia, regardless of tumor location.
Conclusions: In a case-control study of patients with PDAC from 2 databases, we associated FBG level with time to PDAC diagnosis and tumor volume and grade. Patients are hyperglycemic for a mean period of 36 to 30 months before PDAC diagnosis; this information might be incorporated into strategies for early detection.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Acknowledgements:
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institute of Health, or the National Institute of Diabetes and Digestive and Kidney Diseases.
The Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases under the following award numbers:
Project Number: | Awardee Organization |
U01DK108326 | Baylor College of Medicine |
U01DK108314 | Cedars-Sinai Medical Center |
U01DK108332 | Indiana University |
U01DK108323 | Kaiser Foundation Research Institute |
U01DK108288 | Mayo Clinic |
U01DK108327 | Ohio State University |
U01DK108300 | Stanford University |
U01DK108320 | University of Florida |
U01DK108306 | University of Pittsburgh |
U01DK108328 | University of Texas MD Anderson Cancer Center |
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