A1 Refereed original research article in a scientific journal
A combined risk score enhances prediction of type 1 diabetes among susceptible children
Authors: Lauric A. Ferrat , Kendra Vehik , Seth A. Sharp, Åke Lernmark , Marian J. Rewers, Jin-Xiong She, Anette-G. Ziegler, Jorma Toppari, Beena Akolkar, Jeffrey P. Krischer, Michael N. Weedon1, Richard A. Oram, William A. Hagopian; TEDDY Study Group & Committees
Publisher: NATURE PUBLISHING GROUP
Publication year: 2020
Journal: Nature Medicine
Journal name in source: NATURE MEDICINE
Journal acronym: NAT MED
Volume: 26
Issue: 8
First page : 1247
Last page: 1255
Number of pages: 21
ISSN: 1078-8956
eISSN: 1546-170X
DOI: https://doi.org/10.1038/s41591-020-0930-4
Self-archived copy’s web address: https://europepmc.org/articles/pmc7556983?pdf=render
Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk(1). However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common(2,3)and is most severe in the very young(4,5), in whom it can be life threatening and difficult to treat(6-9). Autoantibody surveillance programs effectively prevent most ketoacidosis(10-12)but require frequent evaluations whose expense limits public health adoption(13). Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible(14)because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at >= 2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve >= 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.In a study of children with high genetic risk aged 2 years or older, a risk score integrating pancreatic islet autoantibodies, genetic factors and family history is highly predictive of type 1 diabetes in the subsequent 8 years.
