Genetic Predictors of Response to Oral Insulin for Type 1 Diabetes Prevention
Authors' conclusion
Genetic differences distinguish responders from nonresponders to oral insulin for T1D prevention. Genetics may enable precision medicine by identifying individuals likely to benefit from T1D-modifying therapies.
Study context
- Population
- Relatives of individuals with T1D, with stage 1 T1D, in TN07; SS1 characterized by low first-phase insulin releasegenotyped of 560 · SS1 55
- Participants
- 552 relatives
- Comparison
- Genetic factors and response to oral insulin
- Primary endpoint
- Association between genetic factors and response to oral insulin (prevention of stage 3 T1D)
Methodological detailsgenetic association study, Cox models, Benjamini-Hochberg correction for multiple comparisons
- Genetic association study
- Cox models
- Benjamini-Hochberg correction for multiple comparisons
Primary result
As reported in the abstract
GLIS3 rs7020673 and response to oral insulin in SS1
- GLIS3 rs7020673 significantly associated with response to oral insulin in SS1, without covariate adjustment
- Benjamini-Hochberg (BH)-corrected P = 0.031
- GLIS3 rs7020673 significantly associated with response to oral insulin in SS1, with covariate adjustment
- BH-corrected P = 0.022
Further findings
HLA-DRB1*04:01-DQA1*03:01-DQB1*03:02 and response in SS1 (nominal)
- Better response with haplotype: HR 0.22 vs. 1.09
- unadjusted P = 0.031; adjusted P = 0.045
- Nominal association
TNFAIP3 and CTLA4 (nominal)
- Worse responses with TNFAIP3 and CTLA4 in at least one stratum
- Nominal association
T1D-GRS2 >12.5 vs ≤12.5, overall cohort (exploratory)
- Better response with T1D-GRS2 >12.5 (HR 0.68) than ≤12.5 (HR 2.10)
- unadjusted P = 0.003; adjusted P = 0.006
- Exploratory analysis
T2D polygenic scores (exploratory)
- Lower proinsulin- and obesity-partitioned T2D polygenic scores associated with greater treatment benefit in SS1 and in another secondary stratum, respectively
- Exploratory analysis
Original publication
Genetic Predictors of Response to Oral Insulin for Type 1 Diabetes Prevention. Diabetes Care. Published 9 December 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →