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Immunology and Transplantation

Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size

  1. James J. Ross1,
  2. Clive H. Wasserfall1,
  3. Rhonda Bacher2,
  4. Daniel J. Perry1,
  5. Kieran McGrail1,
  6. Amanda L. Posgai1,
  7. Xiaoru Dong2,
  8. Andrew Muir3,
  9. Xia Li4,5,
  10. Martha Campbell-Thompson1,6,
  11. Todd M. Brusko1,7,
  12. Desmond A. Schatz7,
  13. Michael J. Haller7 and
  14. Mark A. Atkinson1,7⇑
  1. 1Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL
  2. 2Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL
  3. 3Department of Pediatrics, Emory University, Atlanta, GA
  4. 4Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
  5. 5National Clinical Research Center for Metabolic Diseases, Changsha, China
  6. 6Department of Biomedical Engineering, College of Engineering, University of Florida, Gainesville, FL
  7. 7Department of Pediatrics, University of Florida Diabetes Institute, Gainesville, FL
  1. Corresponding author: Mark A. Atkinson, atkinson{at}ufl.edu
Diabetes 2021 Apr; 70(4): 944-954. https://doi.org/10.2337/db20-0995
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Abstract

Exocrine pancreas abnormalities are increasingly recognized as features of type 1 diabetes. We previously reported reduced serum trypsinogen levels and in a separate study, smaller pancreata at and before disease onset. We hypothesized that three pancreas enzymes (amylase, lipase, and trypsinogen) might serve as serological biomarkers of pancreas volume and risk for type 1 diabetes. Amylase, lipase, and trypsinogen were measured from two independent cohorts, together comprising 800 serum samples from single-autoantibody–positive (1AAb+) and multiple-AAb+ (≥2AAb+) subjects, individuals with recent-onset or established type 1 diabetes, their AAb-negative (AAb−) first-degree relatives, and AAb− control subjects. Lipase and trypsinogen were significantly reduced in ≥2AAb+, recent-onset, and established type 1 diabetes subjects versus control subjects and 1AAb+, while amylase was reduced only in established type 1 diabetes. Logistic regression models demonstrated trypsinogen plus lipase (area under the receiver operating characteristic curve [AUROC] = 81.4%) performed equivalently to all three enzymes (AUROC = 81.4%) in categorizing ≥2AAb+ versus 1AAb+ subjects. For cohort 2 (n = 246), linear regression demonstrated lipase and trypsinogen levels could individually and collectively serve as indicators of BMI-normalized relative pancreas volume (RPVBMI, P < 0.001), previously measured by MRI. Serum lipase and trypsinogen levels together provide the most sensitive serological biomarker of RPVBMI and may improve disease staging in pretype 1 diabetes.

Footnotes

  • Clinical trial reg. no. NCT02234947, clinicaltrials.gov

  • This article contains supplementary material online at https://doi.org/10.2337/figshare.13516922.

  • Received October 1, 2020.
  • Accepted January 1, 2021.
  • © 2021 by the American Diabetes Association
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Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size
James J. Ross, Clive H. Wasserfall, Rhonda Bacher, Daniel J. Perry, Kieran McGrail, Amanda L. Posgai, Xiaoru Dong, Andrew Muir, Xia Li, Martha Campbell-Thompson, Todd M. Brusko, Desmond A. Schatz, Michael J. Haller, Mark A. Atkinson
Diabetes Apr 2021, 70 (4) 944-954; DOI: 10.2337/db20-0995

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Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size
James J. Ross, Clive H. Wasserfall, Rhonda Bacher, Daniel J. Perry, Kieran McGrail, Amanda L. Posgai, Xiaoru Dong, Andrew Muir, Xia Li, Martha Campbell-Thompson, Todd M. Brusko, Desmond A. Schatz, Michael J. Haller, Mark A. Atkinson
Diabetes Apr 2021, 70 (4) 944-954; DOI: 10.2337/db20-0995
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