Changes in pancreatic exocrine function in young at-risk children followed to islet autoimmunity and type 1 diabetes in the ENDIA study

Megan A S Penno; Helena Oakey; Priya Augustine; Mario Taranto; Simon C Barry; Peter G Colman; Maria E Craig; Elizabeth A Davis; Lynne C Giles; Mark Harris; Aveni Haynes; Kelly McGorm; Grant Morahan; Claire Morbey; William D Rawlinson; Richard O Sinnott; Georgia Soldatos; Rebecca L Thomson; Peter J Vuillermin; John M Wentworth; Leonard C Harrison; Jennifer J Couper

doi:10.1111/pedi.13056

Changes in pancreatic exocrine function in young at-risk children followed to islet autoimmunity and type 1 diabetes in the ENDIA study

Pediatr Diabetes. 2020 Sep;21(6):945-949. doi: 10.1111/pedi.13056. Epub 2020 Jun 9.

Authors

Megan A S Penno¹, Helena Oakey¹, Priya Augustine², Mario Taranto³, Simon C Barry¹, Peter G Colman⁴, Maria E Craig^{5

6}, Elizabeth A Davis⁷, Lynne C Giles⁸, Mark Harris^{9

10}, Aveni Haynes⁷, Kelly McGorm¹, Grant Morahan¹¹, Claire Morbey¹², William D Rawlinson^{13

14}, Richard O Sinnott¹⁵, Georgia Soldatos^{16

17}, Rebecca L Thomson¹, Peter J Vuillermin^{18

19}, John M Wentworth^{4

20}, Leonard C Harrison²⁰, Jennifer J Couper^{1

2}

Affiliations

¹ Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
² Department of Diabetes and Endocrinology, Women's and Children's Hospital, Adelaide, South Australia, Australia.
³ PathWest Laboratories, Fiona Stanley Hospital Network, Murdoch, Western Australia, Australia.
⁴ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁵ School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁶ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁷ Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
⁸ Robinson Research Institute, School of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
⁹ The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.
¹⁰ Endocrinology Department, Queensland Children's Hospital, South Brisbane, Queensland, Australia.
¹¹ Centre for Diabetes Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, Western Australia, Australia.
¹² Hunter Diabetes Centre, Newcastle, New South Wales, Australia.
¹³ Virology Research Laboratory, Serology and Virology Division, South Eastern Area Laboratory Services Microbiology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
¹⁴ School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ Melbourne eResearch Group, School of Computing and Information Services, University of Melbourne, Melbourne, Victoria, Australia.
¹⁶ Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁷ Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Victoria, Australia.
¹⁸ Faculty of Health, School of Medicine, Deakin University, Geelong, Victoria, Australia.
¹⁹ Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia.
²⁰ Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

PMID: 32430977
DOI: 10.1111/pedi.13056

Abstract

Backgrounds: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

Methods: Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors.

Results: Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P = .02); in some progressors the fall in FE-1 preceded the onset of IA.

Conclusions: Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D.

Keywords: children; exocrine pancreas; fecal elastase; islet autoimmunity; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies / blood
Autoimmunity / physiology*
Biomarkers / analysis
Case-Control Studies
Child, Preschool
Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 1* / immunology
Diabetes Mellitus, Type 1* / pathology
Diabetes Mellitus, Type 1* / physiopathology
Disease Progression
Environment
Feces / chemistry
Female
Humans
Infant
Islets of Langerhans / immunology*
Longitudinal Studies
Male
Pancreas, Exocrine / immunology
Pancreas, Exocrine / physiology*
Pancreatic Elastase / analysis
Risk Factors

Substances

Autoantibodies
Biomarkers
Pancreatic Elastase

Associated data

ANZCTR/ACTRN1261300794707