Insulin resistance in type 1 diabetes is a key modulator of platelet hyperreactivity
Authors' conclusion
Our novel characterisation of platelets in type 1 diabetes shows a maladaptive phenotype with increased basal activity together with hyperactivation following stimulation and diminished responses to inhibition. Insulin resistance appears to further drive this adverse thrombotic phenotype, suggesting an enhanced platelet-driven cardiovascular risk in those with type 1 diabetes and reduced insulin sensitivity.
Study context
- Population
- Individuals with T1D in the DEVELOP study; median age 24 (range 18–34) years, 59% male, diabetes duration 14.0 ± 6.3 years, HbA1c 65.3 ± 14.0 mmol/mol (8.1%)
- Participants
- 32 individuals
- Comparison
- T1D vs healthy controls; advanced insulin resistance vs normal insulin sensitivity within T1D
- Type 1 diabetesn = 32
- Outcome
- Basal platelet activation marker expression (mean fluorescence intensity)
Methodological detailswhole blood multiparameter flow cytometry, machine learning (FAUST) platelet subpopulation analysis
- Whole blood multiparameter flow cytometry
- Machine learning (FAUST) platelet subpopulation analysis
Main finding
As reported in the abstract
CD62P expression
521 ± 246 vs 335 ± 67
P < 0.001
Type 1 diabetes
PAC-1
370 ± 165 vs 231 ± 88
P = 0.011
Type 1 diabetes
Phosphatidylserine (PS)
869 ± 762 vs 294 ± 109
P = 0.001
Type 1 diabetes
Further findings
| Outcome | Advanced insulin resistance | Normal insulin sensitivity | P value |
|---|---|---|---|
| Stimulated platelet activation (single agonist): CD62P expression, advanced insulin resistance vs normal insulin sensitivity | 29,167 (SD 2177) | 22,829 (SD 2535) | P < 0.001 |
| Stimulated platelet activation (single agonist): PAC-1, advanced insulin resistance vs normal insulin sensitivity | 19,339 (SD 11,749) | 5187 (SD 2872) | P = 0.02 |
| Suppression of stimulated CD62P by PGI2Advanced insulin resistance vs Normal insulin sensitivity | 17 (SD 11) % | 33 (SD 12) % | P = 0.02 |
| Suppression of stimulated PAC-1 by PGI2Advanced insulin resistance vs Normal insulin sensitivity | 48 (SD 17) % | 75 (SD 7) % | P = 0.006 |
| Suppression of stimulated PS exposure by PGI2Advanced insulin resistance vs Normal insulin sensitivity | 33 (SD 12) % | 84 (SD 10) % | P = 0.001 |
FAUST platelet subpopulations
- Different distribution of the eight platelet subpopulations, advanced insulin resistance vs normal insulin sensitivity, under basal conditions and after PGI2 inhibition
Original publication
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