Pancreatic Exocrine Dysfunction Occurs After Islet Autoimmunity in T1D

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Pancreatic exocrine dysfunction was not present at time of initial detection of islet cell autoimmunity.
Pancreatic exocrine dysfunction was not present at time of initial detection of islet cell autoimmunity.

Defects in pancreatic exocrine function appear following development of islet autoimmunity in pediatric patients with newly diagnosed type 1 diabetes (T1D), according to study findings published in Pediatric Diabetes.1 These results suggest that pancreatic exocrine dysfunction develops after initiation of islet cell autoimmunity and is related to diabetes disease pathogenesis as opposed to an inherited genetic predisposition.

Investigators in this prospective study sought to find out whether the appearance of islet autoantibodies is associated with reduced exocrine function in pediatric patients with human leukocyte antigen (HLA)-conferred susceptibility. Stool elastase concentrations were measured and served as surrogate biomarkers of exocrine pancreas function.

According to the findings, levels of elastase were not significantly different in cases (n=53) or controls (n=53) during islet autoantibody seroconversion (mean 1013 vs 1203 μg/g; median 738 vs 877 μg/g, P =.149). A total of 5 case children had elastase levels <200 μg/g vs 1 child in the control group (P =.093).

In addition, a total of 41 study participants developed diabetes during the observance period. Overall, levels of elastase were lower at the time of diabetes diagnosis in case children vs controls (mean 355 vs 828 μg/g; median 230 vs 483 μg/g, P =.0006).

Although there was a trend for faster progression to diabetes in patients with low elastase levels (P =.1033 in linear regression analysis), the levels did not fully explain the progression rate.

 

These results suggest that exocrine dysfunction develops in a subset of pediatric patients during disease progression from islet cell autoantibody production to full clinical T1D.  “This suggests that in most cases the defect in the function of the exocrine pancreas develops after the initiation of islet autoimmunity...[indicating] that this defect is linked to the diabetic disease process per se and is not an inherited character of diabetic patients,” the study investigators noted.

According to the investigators, this study does not explain whether or not exocrine dysfunction is a result of the processes that occur during beta-cell damaging. Also, this analysis primarily focused on young children, making generalization of the findings difficult.

The finding that exocrine dysfunction develops “during the progression of islet autoimmunity to clinical type 1 diabetes” may ultimately create new opportunities for using “elastase levels as a biomarker for the progression of the beta-cell damaging process.”

Reference

Kondrashova A, Nurminen N, Lehtonen J, et al. Exocrine pancreas function decreases during the progression of the beta-cell damaging process in young prediabetic children. Pediatr Diabetes [published online October 17, 2017]. doi:10.1111/pedi.12592

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