Exocrine Pancreatic Function as a Novel Biomarker in Pre-T1D

Recent studies demonstrated reduced serum trypsinogen levels as well as pancreatic weight/volume in patients with type 1 diabetes (T1D) and nondiabetic/autoantibody (AAb)-positive subjects. Histological defects including increased CD8⁺ T cell infiltration and elevated C4d deposition have been observed in the exocrine T1D pancreas. Like trypsinogen, amylase and lipase are produced by the exocrine pancreas and serve as more common markers of exocrine function. We hypothesized that amylase and lipase levels would be lower in patients with T1D as well as in subjects with multiple (i.e., ≥2) T1D-related AAb compared with controls. To test this, serum amylase and lipase levels were determined in 70 patients with recent-onset T1D (duration <3 mo), 57 patients with established T1D (duration >3 mo), 56 single AAb positive (1AAb+) subjects, 42 multiple AAb positive (≥2AAb+) subjects, 96 AAb negative (AAb-) relatives of T1D patients, and 110 AAb- control subjects. Amylase levels, which are independent of age (r = -0.02, P = 0.7), were significantly lower in patients with T1D (mean ± SD 39.98 ± 17.8 ng/mL; P < 0.005) vs. AAb- subjects (47.40 ± 20.17 ng/mL). Lipase levels, which are positively correlated with age (r = 0.30, P < 0.0001), were significantly lower in T1D patients (25.95 ± 21.ng/mL; P < 0.001) as well as ≥2AAb+ subjects (22.59 ± 11.12 ng/mL; P < 0.001) compared with 1AAb+ individuals (37.60 ± 16.79 ng/mL). These results provide further evidence that exocrine pancreas abnormalities exist in patients with T1D and ≥2AAb+ subjects considered to have early-stage T1D with high risk of progressing to clinical diagnosis. These data also support the possibility that an inherent or acquired defect in exocrine pancreas development and/or function may contribute to disease pathogenesis, but cause and effect cannot yet be ascertained. Importantly, these exocrine pancreas enzymes may serve as biomarkers of T1D to better predict disease progression and/or stratify patients according to etiology.