Longitudinal Changes in Exocrine Biomarkers in Children at Risk of Type 1 Diabetes in the ENDIA Study
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors
- Fergus J. Cameron (ORCID: https://orcid.org/0000-0002-1566-7436)
- Madeleine Hall (ORCID: https://orcid.org/0009-0002-9130-0190)
- Jason A. Tye–Din (ORCID: https://orcid.org/0000-0001-7687-9654)
- Elizabeth Ann Davis (ORCID: https://orcid.org/0000-0003-4244-5473)
- Rhonda L. Bacher (ORCID: https://orcid.org/0000-0001-5787-476X)
- Rebecca Louise Thomson (ORCID: https://orcid.org/0000-0002-7807-4144)
- Helena Oakey (ORCID: https://orcid.org/0000-0003-1057-7615)
- Wayne A. Rankin (ORCID: https://orcid.org/0000-0002-4427-9547)
- Leonard C. Harrison (ORCID: https://orcid.org/0000-0002-2500-8944)
- John M. Wentworth (ORCID: https://orcid.org/0000-0002-5197-3529)
- Grant Morahan (ORCID: https://orcid.org/0000-0002-8562-7325)
- Tony Huynh (ORCID: https://orcid.org/0000-0002-7909-3670)
- James D. Brown (ORCID: https://orcid.org/0000-0001-5190-4833)
- Mark A. Atkinson (ORCID: https://orcid.org/0000-0001-8489-4782)
- Georgia Soldatos
- Jennifer Couper (ORCID: https://orcid.org/0000-0003-4448-8629)
- Megan A. S. Penno (ORCID: https://orcid.org/0000-0002-9617-0826)
- Maria E. Craig (ORCID: https://orcid.org/0000-0001-6004-576X)
- Aveni Haynes (ORCID: https://orcid.org/0000-0001-9954-5016)
- Emma E. Hamilton‐Williams (ORCID: https://orcid.org/0000-0003-4892-3691)
- Kelly J. McGorm (ORCID: https://orcid.org/0000-0002-7893-6998)
- Clive Henry Wasserfall (ORCID: https://orcid.org/0000-0002-3522-8932)
- Martha Campbell‐Thompson (ORCID: https://orcid.org/0000-0001-6878-1235)
- Simon Charles Barry (ORCID: https://orcid.org/0000-0002-0597-7609)
- William D. Rawlinson (ORCID: https://orcid.org/0000-0001-9238-0546)
- Timothy Spelman
- Peter J. Vuillermin
- ENDIA Study Group*
- Ki Wook Kim
Institutions
- South Australia Pathology (AU)
- The University of Sydney (AU)
- Royal Adelaide Hospital (AU)
- The Royal Melbourne Hospital (AU)
- Barwon Health (AU)
- Royal Children's Hospital (AU)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- The Kids Research Institute Australia (AU)
- The University of Western Australia (AU)
- Princess Margaret Hospital for Children (AU)
- University of Florida Health (US)
- Women's and Children's Hospital (AU)
- Children's Hospital at Westmead (AU)
- Westmead Hospital (AU)
- UNSW Sydney (AU)
- University of Florida (US)
- Monash Health (AU)
- Murdoch Children's Research Institute (AU)
- Children's Health Queensland Hospital and Health Service (AU)
- Perth Children's Hospital (AU)
- Adelaide University (AU)
- Monash University (AU)
- The University of Adelaide (AU)
- St Vincents Institute of Medical Research (AU)
Publication Details
- Journal
- Diabetes Care
- Published
- 2026-11-02
- DOI
- https://doi.org/10.2337/dc26-1627
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Breakthrough T1D