Longitudinal Changes in Exocrine Biomarkers in Children at Risk of Type 1 Diabetes in the ENDIA Study.

Authors

Madeleine Hall, Megan A S Penno, Timothy Spelman, Rhonda Bacher, James D Brown, Wayne A Rankin, Dao Huynh, Elizabeth A Davis, Maria E Craig, Tony Huynh, John M Wentworth, Fergus J Cameron, Georgia Soldatos, Peter J Vuillermin, Mark A Atkinson, Martha L Campbell-Thompson, Clive H Wasserfall, Jennifer J Couper, ENDIA Study Group*

Published in

Diabetes care. Nov 02, 2026. Epub Nov 02, 2026.

Abstract

The exocrine pancreas is increasingly implicated in type 1 diabetes. Noninvasive biomarkers of exocrine function, fecal elastase-1 (FE-1) and serum immunoreactive trypsin (IRT), may provide early insight into disease pathogenesis. We investigated the temporal relationship between exocrine biomarkers and type 1 diabetes development in children.
FE-1 and IRT concentrations were measured prospectively in 301 at-risk children followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort from birth. A total of 216 children provided 1,679 stool samples; 242 provided 1,014 serum samples. Biomarker trajectories were compared between children who developed islet autoimmunity or type 1 diabetes and age- and sex-matched control children negative for autoantibodies in a nested case-control design. Adjusted linear mixed models were used.
Two biomarker patterns were observed. FE-1 concentrations were lower during the first 6 months of life in children who subsequently developed multiple islet autoantibodies or type 1 diabetes (β-coefficient at birth -0.61 [95% CI -1.04, -0.17]; P = 0.006; β-coefficient at 3 months -0.39 [95% CI -0.69, -0.09]; P = 0.010); IRT concentrations were lower in children who developed type 1 diabetes 12 months (β = -0.30 [95% CI -0.58, -0.02]; P = 0.034) and 18 months (β = -0.40 [95% CI -0.71, -0.10]; P = 0.008) before type 1 diabetes diagnosis.
Changes in exocrine biomarkers were detectable early in the natural history of type 1 diabetes, with a delayed rise of FE-1 in infants who later progressed to multiple islet autoantibodies or type 1 diabetes and a decrease in IRT following islet autoantibody seroconversion.

PMID:
42969688
Bibliographic data and abstract were imported from PubMed on 02 Nov 2026.

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