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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.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

    ,

    Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.

    ,

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

    ,

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: chari.suresh@mayo.edu.

    Source

    Gastroenterology 155:2 2018 08 pg 490-500.e2

    MeSH

    Aged
    Blood Glucose
    Carcinoma, Pancreatic Ductal
    Case-Control Studies
    Diabetes Mellitus
    Disease Progression
    Fasting
    Female
    Humans
    Hyperglycemia
    Male
    Middle Aged
    Minnesota
    Pancreas
    Pancreatic Neoplasms
    Time Factors
    Tumor Burden

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    29723506

    Citation

    Sharma, Ayush, et al. "Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis." Gastroenterology, vol. 155, no. 2, 2018, pp. 490-500.e2.
    Sharma A, Smyrk TC, Levy MJ, et al. Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. Gastroenterology. 2018;155(2):490-500.e2.
    Sharma, A., Smyrk, T. C., Levy, M. J., Topazian, M. A., & Chari, S. T. (2018). Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. Gastroenterology, 155(2), pp. 490-500.e2. doi:10.1053/j.gastro.2018.04.025.
    Sharma A, et al. Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. Gastroenterology. 2018;155(2):490-500.e2. PubMed PMID: 29723506.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. AU - Sharma,Ayush, AU - Smyrk,Thomas C, AU - Levy,Michael J, AU - Topazian,Mark A, AU - Chari,Suresh T, Y1 - 2018/04/30/ PY - 2017/11/13/received PY - 2018/03/22/revised PY - 2018/04/25/accepted PY - 2019/08/01/pmc-release PY - 2018/5/4/pubmed PY - 2018/8/14/medline PY - 2018/5/4/entrez KW - Biomarker KW - Early Detection KW - Sojourn Time KW - Time Course Study SP - 490 EP - 500.e2 JF - Gastroenterology JO - Gastroenterology VL - 155 IS - 2 N2 - 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/29723506/Fasting_Blood_Glucose_Levels_Provide_Estimate_of_Duration_and_Progression_of_Pancreatic_Cancer_Before_Diagnosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(18)30486-4 DB - PRIME DP - Unbound Medicine ER -