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

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 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 (RPV<sub>BMI</sub>, <i>P</i><0.001), previously measured by magnetic resonance imaging. Serum lipase and trypsinogen levels together provide the most sensitive serological biomarker of RPV<sub>BMI</sub> and may improve disease staging in pre-type 1 diabetes.

Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

“…In fulminant T1D, elevations in lipase and amylase have also been reported at presentation (42). Conversely, in the classic T1D phenotype serum lipase and trypsinogen have also been shown to be significantly lower in patients with both T1D patients and patients positive for multiple autoantibodies in comparison to controls (86). Histology of pancreata from T1D patients shows immune cell infiltrate and fibrosis within exocrine tissue (43,87), C4d complement deposition within exocrine ducts (88) and reduced acinar cell numbers (87).…”

Proteome mapping of the human pancreatic islet microenvironment reveals endocrine-exocrine signaling sphere of influence

“…In addition to insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and several neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) have been shown to be involved in this islet-acinar connection; regulating the functions of each tissue type 9 . Through causes we do not yet understand, people with type 1 diabetes and their first-degree relatives have also been shown to have overall reduced pancreatic volume compared to matched controls and some evidence supports exocrine pancreas atrophy and exocrine insufficiency in people with long term T1D [10][11][12] . The more we learn about this endocrine-exocrine/islet-acinar connection the greater its importance appears to be in understanding diseases involving the pancreas.…”