Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis

Abstract

Background & 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.

Keywords: Biomarker; Early Detection; Sojourn Time; Time Course Study.

Conflict of interest statement

Conflict of interest: No conflict of interest declared

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Cohort A: Temporal glycemic profile of population-based controls and pancreatic cancer up to 60 months before index date (see also supplementary table 3) Abbreviations: THG, onset of hyperglycemia; TDM, onset of diabetes; TDX, cancer diagnosis

Figure 2

Cohort B: Cross-sectional glycemic profile of controls (non-tumor bearing) and resected pancreatic cancer subjects stratified by tumor volume (see also supplementary table 4) Abbreviations: VHG, volume associated with hyperglycemia; VDM, volume associated with diabetes; VDX, median volume at diagnosis

Figure 3

Fasting blood glucose, CA19-9 and lymph node involvement with increasing tumor volume of pancreatic cancer Abbreviations: VHG, volume associated with hyperglycemia; VDM, volume associated with diabetes; VDX, median volume at diagnosis

Figure 4

Cohort C: Temporal glycemic profile of population-based controls and resected pancreatic cancer subjects stratified by tumor volume up to 48 months before index date (see also supplementary table 5)

Figure 5

Pre- and post-operative fasting blood glucose in resected pancreatic cancer patients by location of tumor and type of surgical resection (see also supplementary table 6)

Figure 6

A. Cohort A: Temporal glycemic profile of population-based controls and pancreatic cancer after excluding subjects with diabetes at baseline (60 to 54 months) (see also supplementary table 7). Figure 6.B: Temporal glycemic profile of population-based controls and large resected (>16.0 cc), intermediate and small resected (<16.0 cc) and un-resected pancreatic cancer subjects up to 48 months before index date (see also supplementary table 8) Abbreviations: THG, onset of hyperglycemia; TDM, onset of diabetes