Longitudinal Changes in Exocrine Biomarkers in Children at Risk of Type 1 Diabetes in the ENDIA Study
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, , Simon C. Barry, Emma E. Hamilton-Williams, Leonard C. Harrison, Aveni Haynes, Ki Wook Kim, Kelly McGorm, Grant Morahan, Helena Oakey, William D. Rawlinson, Rebecca L. Thomson, Jason A. Tye-DinOBJECTIVE
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.