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

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 (RPV_BMI, P < 0.001), previously measured by MRI. Serum lipase and trypsinogen levels together provide the most sensitive serological biomarker of RPV_BMI and may improve disease staging in pretype 1 diabetes.