Age-independent immune subtypes in type 1 diabetes exhibit distinct post-onset progression rates and immunotherapeutic responses
Authors' conclusion
These findings support the existence of immunologically distinct type 1 diabetes subgroups and the possibility of future targeted therapeutic interventions.
Study context
- Population
- Individuals with new-onset T1D in six immunotherapy trials
- Participants
- 560 individuals6 trials
- Comparison
- Immune subgroup 1 vs subgroup 2
- Outcome
- Immune subtypes by plasma-induced transcription
- Follow-up
- Baseline
Methodological detailspre-intervention samples from six immunotherapy trials, plasma-induced transcriptional bioassay, unsupervised clustering
- Pre-intervention samples from six immunotherapy trials
- Plasma-induced transcriptional bioassay
- Unsupervised clustering
Main finding
As reported in the abstract
- Transcripts with high variation in at least five trials
- 2854
- Subgroup classifications stable in post-baseline longitudinal samples
- p=1.4 × 10-14
Further findings
Subgroup 1 phenotype
- Youngest participants in subgroup 1 had the most rapid rate of C-peptide decline
- P < 0.05
- Increased circulating CD4+CXCR3+CCR6- Th1 T cells
- P < 0.05
- Elevated plasma cytokine and chemokine levels; better therapeutic response to anti-CD20
Subgroup 2 phenotype
- Higher plasma miR-155-5p and miR-409-3p
- P < 0.05
- Better response to CTLA4-Ig linked to greater reduction in CD4+CD45RO+CD62L+ central memory T cells
- P = 8.1 × 10-5
- Retention of regulatory T cells
- P = 0.02
Original publication
Age-independent immune subtypes in type 1 diabetes exhibit distinct post-onset progression rates and immunotherapeutic responses. Diabetologia. Published 11 July 2026. doi:10.
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