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

• Authors: James J Ross, University of Florida; Clive H Wasserfall, University of Florida; Rhonda Bacher, University of Florida; Daniel J Perry, University of Florida; Kieran McGrail, University of Florida; Amanda L Posgai, University of Florida; Xiaoru Dong, University of Florida; Andrew Muir, Emory University; Xia Li, Central South University; Martha Campbell-Thompson, University of Florida; Todd M Brusko, University of Florida; Desmond A Schatz, University of Florida; Michael J Haller, University of Florida; Mark A Atkinson, University of Florida
• Journal Title: DIABETES
• Volume: Volume 70, Number 4
• Publisher: AMER DIABETES ASSOC | 2021-04-01, Pages 944-954
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.2337/db20-0995
• Subjects: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Biostatistics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; PATHOLOGICAL ANATOMY; SERUM AMYLASE; RISK SCORE; LIPASE; TRYPSINOGEN; ENDOCRINE; ORGAN; ASSAY; INFILTRATION; PARTICIPANTS

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.