Pathway‐Specific Polygenic Risk Score and Risk of Hyperglycaemic Progression in Patients With Type 2 Diabetes
Authors' conclusion
psPRS for metabolic syndrome is nominally associated with risk of hyperglycaemic progression in multi-ancestry Southeast Asian people with type 2 diabetes. The psPRS does not provide incremental value for prediction of hyperglycaemic progression beyond clinical risk predictors.
Study context
- Population
- Insulin-naïve Southeast Asian outpatients with T2D from a secondary hospital and a primary care facility
- Participants
- 1,059 outpatients
- Exposure
- Pathway-specific polygenic risk scores (psPRS) for beta cell dysfunction, obesity and metabolic syndrome
- Outcome
- Hyperglycaemic progression: sustained insulin therapy lasting longer than 6 months
- Follow-up
- Median 11.2 (8.9-11.8) years
Methodological detailsgenetic association study
- Genetic association study
Main finding
As reported in the abstract
Hyperglycaemic progression · median 11.2 (8.9-11.8) years
Participants initiating sustained insulin therapy
188
Metabolic syndrome psPRS, per 1 SD increment: aHR (adjusted for clinical risk factors)
1.17
1.02–1.36
Observational data: associations, not effects.
Further findings
| Outcome | Delta AUC (95% CI) | P value |
|---|---|---|
| Risk discrimination: adding metabolic syndrome psPRS to clinical predictors (diabetes onset age, HbA1c, HDL-C, eGFR, urinary albumin-to-creatinine ratio)Clinical predictors + metabolic syndrome psPRS vs Clinical predictors | −0.01 (−0.02 to 0.01) | P = 0.50 |
Composite of sustained insulin therapy and requirement for insulin treatments (HbA1c > 8.5% with ≥2 non-insulin medications)
- Consistent results with metabolic syndrome psPRS
Original publication
Pathway‐Specific Polygenic Risk Score and Risk of Hyperglycaemic Progression in Patients With Type 2 Diabetes. Diabetes Obes Metab. Published 1 September 2026. doi:10.
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