Milder loss of insulin-containing islets in individuals with type 1 diabetes and type 2 diabetes-associated TCF7L2 genetic variants
Main finding · High ICI% (≥5)Result — go to the resultLikelihood of high ICI% (adjusted) 2.93 95% CI 1.02–8.47Authors' conclusion
Overall, these data support the presence of a type 1 diabetes endotype associated with a genetic factor that predisposes to type 2 diabetes, with donors in this category exhibiting less severe beta cell loss. It is possible that in these individuals the disease pathogenesis may include mechanisms associated with type 2 diabetes and thus this may provide an explanation for the poor response to immunotherapies to prevent type 1 diabetes or its progression in a subset of individuals. If so, strategies that target both type 1 diabetes and type 2 diabetes-associated factors when they are present may increase the success of prevention and treatment in these individuals.
Study context
- Population
- nPOD donors with T1D; mean±SD age at onset 12.2±7.9 years, diabetes duration 15.3±13.7 years, 53% male, 80% non-Hispanic White
- Participants
- 110 donors
- Exposure
- TCF7L2 rs7903146 T allele carriers vs non-carriers
- Outcome
- High percentage of residual insulin-containing islets (ICI% ≥5)
Methodological detailsnPOD organ donor programme, genomic and pancreatic tissue analysis
- nPOD organ donor programme
- Genomic and pancreatic tissue analysis
Main finding
High ICI% (≥5)
Likelihood of high ICI% (adjusted)
2.93
95% CI 1.02–8.47
P = 0.047
As reported in the abstract
- T allele carriers (TC or TT)
- 45.5%
Observational data: associations, not effects.
Further findings
Characteristics of high ICI% (≥5) vs low ICI% (<5) donors · older at onset with high ICI%
P = 0.013
Age at onset (years) High ICI% 15.3±6.9 · Low ICI% 11.1±8
Diabetes duration (years) High ICI% 7.0±7.4 · Low ICI% 18.5±14.3
African ancestry score High ICI% 0.2±0.3 · Low ICI% 0.1±0.2
European ancestry score High ICI% 0.7±0.3 · Low ICI% 0.9±0.3
| Outcome | P value |
|---|---|
| Characteristics of high ICI% (≥5) vs low ICI% (<5) donorsShorter duration with high ICI% | P < 0.001 |
| Characteristics of high ICI% (≥5) vs low ICI% (<5) donorsHigher with high ICI% | P = 0.043 |
| Characteristics of high ICI% (≥5) vs low ICI% (<5) donorsLower with high ICI% | P = 0.023 |
ICI% in all donors
- Mean ± SD ICI%
- 9.8±21.5 (range 0-92.2)
Original publication
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