- The Diabetogenic Effect of Statin Use May Interact With Polygenic Risk Scores for Type 2 Diabetes: Evidence From the UK Biobank
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Jong Hyun Park, Kyu-Taek Lim, Jooyeon Lee, Yongjin Gil, Joohon Sung
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J Prev Med Public Health. 2025;58(1):92-102. Published online December 11, 2024
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DOI: https://doi.org/10.3961/jpmph.24.671
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 Abstract
Summary
 PDF Supplementary Material
- Objectives
Statins are essential in the prevention of cardiovascular disease; however, their association with type 2 diabetes mellitus (T2DM) risk is concerning. We examined whether genetic susceptibility to T2DM modifies the association between regular statin use and T2DM risk.
Methods
This study included 447 176 individuals from the UK Biobank without baseline diabetes or major cardiovascular disease. Statin use was recorded at baseline, and T2DM incidence was determined using clinical records. Polygenic risk scores (PRS) for T2DM risk were provided by the UK Biobank. Using propensity scores adjusted for age, sex, body mass index, and comorbidities, 14 831 statin users were matched with 37 060 non-users. Cox proportional hazards models were used to estimate the interaction effect of statin use and PRS on T2DM incidence, adjusting for key confounders.
Results
In the propensity-matched cohort, 3675 of 51 891 participants developed T2DM over a mean follow-up period of 13.7 years. Within the top 5% of the PRS distribution, per 1000 person-years, the incidence of T2DM was 15.42 for statin users versus 12.18 for non-users. Among the lowest 5%, the incidence was 1.90 for statin users and 1.65 for non-users. Based on the Cox proportional hazards model, regular statin use was associated with a 1.24-fold increased T2DM risk (95% confidence interval [CI], 1.15 to 1.33). Furthermore, PRS exhibited a significant multiplicative interaction with regular statin use (odds ratio, 1.10; 95% CI, 1.02 to 1.19).
Conclusions
PRS may help identify individuals particularly susceptible to the diabetogenic effects of statins, providing a potential path for personalized cardiovascular disease management.
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Summary
Korean summary
스타틴은 심혈관 질환 예방에 필수적이지만, 제2형 당뇨병 발생 위험을 높인다고 알려져 있습니다. 본 연구는 영국 바이오뱅크 데이터를 활용하여, 스타틴 사용과 제2형 당뇨병 다유전자 위험 점수(Polygenic Risk Score, PRS)의 상호작용이 당뇨병 발생 위험에 미치는 영향을 분석했습니다. 연구 결과, PRS가 높은 집단에서는 스타틴 사용이 제2형 당뇨병 발생 위험을 유의하게 증가시켰으나, PRS가 낮은 집단에서는 스타틴 사용이 오히려 당뇨병 위험을 낮추는 경향을 보였습니다. 이러한 결과는 유전적 요인을 고려한 맞춤형 심혈관 질환 예방 전략의 중요성을 시사합니다.
Key Message
This study highlights that the diabetogenic effect of statins interacts significantly with genetic predisposition, as quantified by polygenic risk scores (PRS) for type 2 diabetes mellitus (T2DM). Individuals with high PRS are at a significantly increased risk of developing T2DM with statin use, while those with low PRS may experience a reduced risk. These findings underscore the potential of integrating genetic risk stratification into clinical decision-making to optimize the balance between cardiovascular benefits and T2DM risk in statin therapy.
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