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

Abstract

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.

• Authors: Peter Achenbach, Markus Hippich, Jose Zapardiel-Gonzalo, Beate Karges, Reinhard W Holl, Agnese Petrera, Ezio Bonifacio, Anette-G Ziegler, DiMelli Study group and DPV Study group
• Journal: EBioMedicine (EBioMedicine) Vol. 82 Pg. 104118 (Aug 2022) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 35803018 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Autoantibodies
• C-Peptide
• Glycated Hemoglobin A

Topics

• Adolescent
• Autoantibodies
• Autoimmunity
• C-Peptide
• Child
• Diabetes Mellitus, Type 1 (diagnosis)
• Diabetes Mellitus, Type 2
• Glycated Hemoglobin (analysis)
• Humans
• Young Adult