Type 1 diabetes

ENDIA study tracks pancreatic exocrine decline prior to T1D

Pancreatic exocrine function decreases in the majority of young at-risk children who progress to islet autoimmunity and type 1 diabetes, Australian research has shown.

A study from the longitudinal ENDIA trial, following children with a first degree relative with type 1 diabetes from pregnancy, compared fecal elastase (FE-1) in 257 samples from 85 children.

Progressors (n=28) were children who developed one or more persistent islet autoantibodies and non-progressors (n=57) were islet autoantibody-negative age and gender matched children followed at the same three-monthly intervals.

The study found baseline FE-1 did not differ according to subsequent progression or non progression, HLA DR type, gender, or whether the mother had type 1 diabetes.

However progressors had a significant decrease in FE-1 over time in comparison to non-progressors.

“In the six-month windows before and after IA seroconversion, FE-1 increased by 109μg/g from a predicted mean of 1574 (95% CI 1418,1747) to 1683 (1514,1871) μg/g in non-progressors, but decreased by 95μg/g from a predicted mean of 1676 (95% CI 1479,1899) to 1581 (1397,1790) μg/g in progressors,” the study authors from the Robinson Research Institute at the University of Adelaide said.

No child had FE-1 concentrations below the normal range.

Led  by Professor Jenny Couper, the researchers said the possibility that children who develop T1D have a smaller pancreas from birth is not supported by their finding that baseline FE-1 in the first year of life was similar in progressors and non-progressors.

“This must be qualified, however, by the fact that all children were first-degree relatives of individuals with T1D who could have a smaller pancreatic volume even in the absence of IA.”

They said the decrease in pancreatic volume and exocrine function before the onset of clinical T1D has been attributed to the lack of an insulin-trophic effect on the acinar cells as beta cells are destroyed.

“However, this may not be the complete explanation because we found a decrease in FE-1 before and around the time of seroconversion.”

They noted FE-1 was not a reliable biomarker for progression to type 1 diabetes given factors such as the wide variability in concentrations, the normal increase in FE-1 during the first years of life and the rapid progression to diabetes in this age group.

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