Proteomic signatures of loss of glycemic control in youth-onset type 2 diabetes in the TODAY study
Authors' conclusion
Novel proteins involved in axon guidance, immune response, inflammation, and metabolism associated with LOGC in youth-onset T2D with proteins demonstrating consistent associations across the lifespan and proteomic platforms.
Study context
- Population
- Youth-onset T2D, TODAY study participants (age 14 ± 2 years; 37% male)72% experienced loss of glycemic control (LOGC)
- Participants
- 374 participants
- Outcome
- LOGC: HbA1c ≥ 8% for ≥6 months or inability to discontinue insulin after acute metabolic decompensation
- Follow-up
- Mean 10.8 ± 3.8 years
Methodological detailsmulticenter, external validation in three youth cohorts and one adult-onset T2D cohort
- Multicenter
- External validation in three youth cohorts and one adult-onset T2D cohort
Main finding
As reported in the abstract
Proteins associated with LOGC
Proteins associated with LOGC after false discovery rate correction and multivariable adjustment
67
Plexin-B2, HR
1.46 (1.29-1.66) (95% CI)
Semaphorin-6A, HR
1.31 (1.18-1.47) (95% CI)
Observational data: associations, not effects.
Further findings
Proteomics coverage
- Aptamers quantified (SomaScan 7 K)
- 7604
- Proteins represented
- 6596
External validation
- Plexin-B2 and semaphorin-6A also associated with glycemic outcomes in independent youth and adult cohorts
Enrichment analyses
- Pathways implicated: axon guidance, immune response, inflammation, metabolism
Original publication
Proteomic signatures of loss of glycemic control in youth-onset type 2 diabetes in the TODAY study. J Clin Endocrinol Metab. Published 15 July 2026. doi:10.
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