Transcriptomics of type 1 diabetes progression: a validation study in newly diagnosed patients

Area of Science:

• Immunology
• Endocrinology
• Genomics

Background:

• Type 1 diabetes (T1D) is an autoimmune disease characterized by variable insulin secretion decline post-diagnosis.
• This variability complicates treatment development and disease management.
• Previous research identified gene expression changes within the first year post-T1D diagnosis correlating with C-peptide decline.

Purpose of the Study:

• To validate previously identified gene expression associations with T1D progression in an independent cohort.
• To increase statistical power by combining data from two INNODIA cohorts.
• To further understand the molecular dynamics of T1D progression.

Main Methods:

• Transcriptomic analysis of 168 individuals with newly diagnosed T1D from a follow-up INNODIA cohort.
• Replication of previously identified associations between gene expression and disease progression.
• Integrated analysis of combined data from original and follow-up cohorts, examining longitudinal gene expression changes in the first year post-diagnosis in relation to disease progression, age, and estimated immune cell abundances.

Main Results:

• Longitudinal gene expression changes during the first year post-diagnosis were validated in the follow-up cohort.
• Integrated analysis identified numerous differentially expressed genes within the first year post-T1D onset.
• Rapid T1D progression correlated with younger age and decreased neutrophil abundance; specific gene expression changes were linked to progression rates.

Conclusions:

• Findings support biological heterogeneity in T1D progression post-diagnosis.
• Improved understanding of molecular dynamics associated with T1D progression.
• Potential to aid patient stratification and personalized therapeutic approaches for T1D.