Characterisation and clinical outcomes in children and adolescents with diabetes according to newly defined subgroups: a cohort study from the DPV registry

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Katharina Warncke - , Technical University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Alexander Eckert - , Ulm University, German Center for Diabetes Research (DZD e.V.) (Author)
  • Ezio Bonifacio - , Center for Regenerative Therapies Dresden, University Medicine (Faculty of Medicine and University Hospital), Chair of Preclinical stem cell therapy and diabetes, German Center for Diabetes Research (DZD e.V.) (Author)
  • Peter Achenbach - , German Center for Diabetes Research (DZD e.V.), Technical University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Olga Kordonouri - , Children's Hospital Auf der Bult (Author)
  • Thomas Meissner - , University Hospital Duesseldorf (Author)
  • Ute Ohlenschläger - , University of Hamburg (Author)
  • Walter Bonfig - , Technical University of Munich, Klinikum Wels - Grieskirchen GmbH (Author)
  • Anette G. Ziegler - , German Center for Diabetes Research (DZD e.V.), Technical University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Reinhard W. Holl - , Ulm University, German Center for Diabetes Research (DZD e.V.) (Author)

Abstract

Background: Personalised therapy has emerged as a possibly more efficient approach taking disease heterogeneity into account. The aim of this study was to determine whether recently described subgroups of childhood diabetes have prognostic association with diabetes-specific complications and, therefore, might be a basis for personalised therapies. Methods: We applied a previously developed subgroup classification to pediatric patients (diabetes onset <18 years) from the prospective Diabetes Patient Follow-up (DPV) registry with documented data between January 1, 2000 and March 31, 2022, from diabetes centers in Germany, Austria, Switzerland, and Luxembourg. The classification required information on islet autoantibody status, age, haemoglobin A1c (HbA1c), and body-mass index (BMI-SDS) at disease manifestation, as well as follow up data after 2 and after 4 years, which was available in 22,719 patients. Patients without documented data on these parameters were excluded from the analysis. The cumulative risk of severe hypoglycemia, diabetic ketoacidosis (DKA), retinopathy, and nephropathy were analysed by Kaplan–Meier analyses over a median follow-up of 6.8 years (IQR 4.8–9.6). Findings: Patients were classified into 10 subgroups (P1–P7 islet autoantibody-positive, n = 19,811; N1–N3 islet autoantibody-negative, n = 2908). The groups varied markedly with respect to specific acute and chronic complications. Severe hypoglycemia was a characteristic feature in young islet autoantibody-positive subgroups P1, P3, P4 (10-year risk 46, 46 and 47%) and the islet autoantibody-negative groups N1, N2 (43 and 46%). Nephropathy was identified in patient groups P2 and P5 (10-year risk 16%), which had features of moderate disease such as preserved C-peptide, low HbA1c, and very low frequency of DKA at diabetes onset. Group P7, which was defined by a high BMI, was associated with poor metabolic control, DKA, and retinopathy. In contrast, islet autoantibody-negative patients with high BMI (N3) had a low risk for all four complications. Interpretation: Subgrouping of childhood diabetes at diabetes onset provided prognostic value for the development of acute and chronic diabetes-specific complications. Funding: The DPV initiative is supported by The German Ministry of Education and Research (BMBF) within the German Center for Diabetes Research, the diabetes surveillance of the Robert Koch Institute, the German Diabetes Association (DDG) and INNODIA.

Details

Original languageEnglish
Article number102208
JournalEClinicalMedicine
Volume64
Publication statusPublished - Oct 2023
Peer-reviewedYes

External IDs

ORCID /0000-0002-8704-4713/work/150880747

Keywords

Research priority areas of TU Dresden

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Children, Complications, Diabetes, Personalised medicine, Subgroups