Serum Trypsinogen Levels in Type 1 Diabetes

Abstract

OBJECTIVEThe pancreas in type 1 diabetes exhibits decreased size (weight/volume) and abnormal exocrine morphology. Serum trypsinogen levels are an established marker of pancreatic exocrine function. As such, we hypothesized that trypsinogen levels may be reduced in patients with pre–type 1 diabetes and type 1 diabetes compared with healthy control subjects.RESEARCH DESIGN AND METHODSSerum trypsinogen levels were determined in 100 persons with type 1 diabetes (72 new-onset, 28 established), 99 autoantibody-positive (AAb+) subjects at varying levels of risk for developing this disease, 87 AAb-negative (AAb−) control subjects, 91 AAb− relatives with type 1 diabetes, and 18 patients with type 2 diabetes.RESULTSTrypsinogen levels increased significantly with age in control subjects (r = 0.71; P < 0.0001) and were significantly lower in patients with new-onset (mean ± SD 14.5 ± 6.1 ng/mL; P < 0.0001) and established type 1 diabetes (16.7 ± 6.9 ng/mL; P < 0.05) versus AAb− control subjects (25.3 ± 11.2 ng/mL), AAb− relatives (29.3 ± 15.0 ng/mL), AAb+ subjects (26.5 ± 12.1 ng/mL), and patients with type 2 diabetes (31.5 ± 17.3 ng/mL). Multivariate analysis revealed reduced trypsinogen in multiple-AAb+ subjects (P < 0.05) and patients with type 1 diabetes (P < 0.0001) compared with AAb− subjects (control subjects and relatives combined) and single-AAb+ (P < 0.01) subjects when considering age and BMI.CONCLUSIONSThese findings further support the interplay between pancreatic endocrine and exocrine dysfunction. Longitudinal studies are warranted to validate trypsinogen as a predictive biomarker of type 1 diabetes progression.

Relative Pancreas Volume Is Reduced in First-Degree Relatives of Patients With Type 1 Diabetes

“…Recent studies indicate that there may be autoimmune infiltration of the exocrine portion of the pancreas, and AABs to exocrine proteins have been reported in patients with type 1 diabetes (20,31,41). Exocrine dysfunction has been reported and indicated by reduction in trypsinogen levels in patients with type 1 diabetes and AAB + multiple subjects without diabetes (42). While our study was not powered to make formal comparisons across groups, we observed a trend of lower trypsinogen levels in AAB + multiple subjects and in patients with recent-onset type 1 diabetes, which highlights subclinical exocrine dysfunction in type 1 diabetes.…”

Analysis of pancreatic volume in acute‐onset, slowly‐progressive and fulminant type 1 diabetes in a Japanese population

“…similarly observed abundant CD45‐positive cells infiltrating the exocrine pancreases of non‐diabetic patients who tested positive for islet autoantibody, showing that subclinical pancreatic inflammation begins long before the acute‐onset type 1 diabetes onset. A recent report by Li et al . showed that serum trypsinogen levels are significantly lower in non‐diabetic patients testing double positive for islet autoantibodies compared with seronegative non‐diabetic controls.…”

Large-scale electron microscopy database for human type 1 diabetes

“…20,21 ). Type 1 diabetes patients show a significant reduction in pancreas weight or volume at the time of disease onset, and exocrine insufficiency has been reported [25][26][27][28][29] . Other findings include immunological alterations such as increased incidence of exocrine-specific autoantibodies 30,31 , infiltration of immune cells in exocrine tissue 19,32 , and complement activation localized to vessels and ducts throughout the exocrine tissue 33 .…”