ALT_and_PV_Online_Only_Supplemental_Material_Diabetes.pdf (428.62 kB)
Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size
figure
posted on 2021-01-14, 00:47 authored by 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. AtkinsonExocrine 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 prior to 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- controls. Lipase and trypsinogen were significantly reduced
in ≥2AAb+, recent-onset, and established type 1 diabetes subjects versus controls
and 1AAb+, while amylase was reduced only in established type 1 diabetes. Logistic
regression models demonstrated trypsinogen plus lipase (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 magnetic
resonance imaging. Serum lipase and trypsinogen levels together provide the most
sensitive serological biomarker of RPVBMI and may improve disease
staging in pre-type 1 diabetes.