The 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.

Serum 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.

Trypsinogen 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.

These 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.