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Achenbach, P. ; Hippich, M. ; Zapardiel-Gonzalo, J. ; Karges, B.* ; Holl, R.W.* ; Petrera, A. ; Bonifacio, E.E. ; Ziegler, A.-G.

A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.

EBioMedicine 82:104118 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Diabetes in childhood and adolescence includes autoimmune and non-autoimmune forms with heterogeneity in clinical and biochemical presentations. An unresolved question is whether there are subtypes, endotypes, or theratypes within these forms of diabetes. METHODS: The multivariable classification and regression tree (CART) analysis method was used to identify subgroups of diabetes with differing residual C-peptide levels in patients with newly diagnosed diabetes before 20 years of age (n=1192). The robustness of the model was assessed in a confirmation and prognosis cohort (n=2722). FINDINGS: The analysis selected age, haemoglobin A1c (HbA1c), and body mass index (BMI) as split parameters that classified patients into seven islet autoantibody-positive and three autoantibody-negative groups. There were substantial differences in genetics, inflammatory markers, diabetes family history, lipids, 25-OH-Vitamin D3, insulin treatment, insulin sensitivity and insulin autoimmunity among the groups, and the method stratified patients with potentially different pathogeneses and prognoses. Interferon-ɣ and/or tumour necrosis factor inflammatory signatures were enriched in the youngest islet autoantibody-positive groups and in patients with the lowest C-peptide values, while higher BMI and type 2 diabetes characteristics were found in older patients. The prognostic relevance was demonstrated by persistent differences in HbA1c at 7 years median follow-up. INTERPRETATION: This multivariable analysis revealed subgroups of young patients with diabetes that have potential pathogenetic and therapeutic relevance. FUNDING: The work was supported by funds from the German Federal Ministry of Education and Research (01KX1818; FKZ 01GI0805; DZD e.V.), the Innovative Medicine Initiative 2 Joint Undertaking INNODIA (grant agreement No. 115797), the German Robert Koch Institute, and the German Diabetes Association.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter C-peptide ; Cart Analysis ; Childhood Autoimmune Disease ; Diabetes Endotypes ; Diabetes In Childhood ; Inflammation ; Islet Autoantibody ; Obesity ; Type 1 Diabetes Genetic Susceptibility
ISSN (print) / ISBN 2352-3964
e-ISSN 2352-3964
Zeitschrift EBioMedicine
Quellenangaben Band: 82, Heft: , Seiten: , Artikelnummer: 104118 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)
Institute of Diabetes and Obesity (IDO)
CF Metabolomics & Proteomics (CF-MPC)
Institute for Pancreatic Beta Cell Research (IPI)
Förderungen Bundesministerium für Bildung und Forschung
Juvenile Diabetes Research Foundation United States of America
Leona M. and Harry B. Helmsley Charitable Trust
Union's Horizon 2020
Innovative Medicine Initiative 2 Joint Undertaking
German Robert Koch Institute
German Diabetes Association
Fabian Theis
Competence Network Diabetes Mellitus