High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment
Authors' conclusion
High pre-treatment PI:C identified individuals with stage 2 type 1 diabetes who were exhibiting rapid progression to stage 3 disease and who displayed benefit from teplizumab treatment. These data suggest that readouts of active disease, such as PI:C ratio, could serve to identify optimal candidates or timing for type 1 diabetes disease-modifying therapies.
Study context
- Population
- Participants with stage 2 T1D in the TrialNet Teplizumab Prevention Study; baseline serum proinsulin and C-peptide
- Participants
- 63 participants
- Comparison
- Teplizumab vs placebo, by baseline PI:C ratio
- Teplizumabn = 41
- Placebon = 22reference
- Primary endpoint
- Relationship of baseline intact proinsulin:C-peptide (PI:C) ratio with progression to stage 3 diabetes
Methodological detailslongitudinal
- Longitudinal
Primary result
As reported in the abstract
Progression to stage 3 diabetes by baseline PI:C
- Elevated baseline PI:C strongly associated with more rapid progression in both placebo and teplizumab groups
- Teplizumab abrogated the impact of high pre-treatment PI:C on T1D progression
Further findings
Mechanism of differential response
- Differential responses in high vs low PI:C independent of teplizumab effects on PI:C ratio or relevant immune cells
Original publication
High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment. Diabetologia. Published 4 September 2023. doi:10.
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