TY - JOUR
T1 - Association between insulin-associated gene polymorphisms and new-onset diabetes mellitus in statin-treated patients
AU - Park, Minju
AU - Kim, Jung Sun
AU - Park, Yoon A.
AU - Lee, Da Hoon
AU - Choi, Seo A.
AU - Chang, Yoonkyung
AU - Song, Tae Jin
AU - Gwak, Hye Sun
AU - Yee, Jeong
N1 - Publisher Copyright:
© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.
PY - 2025/4
Y1 - 2025/4
N2 - Background: While statins are effective at managing lipid levels, there is growing evidence for new-onset diabetes mellitus (NODM). The insulin signalling pathway (ISP) inhibited by statins is one of the potential mechanisms; however, most studies have been limited to in vitro settings. Therefore, this study aimed to identify the genetic associations within the ISP-related genes and NODM. Methods: We performed a retrospective analysis of samples collected prospectively from February 2021 to May 2021. Among ISP-related genes, we selected 11 candidate genes (IGF1, IGF2, IGF1R, INSR, IRS1, IRS2, PIK3CA, PIK3CB, PIK3R1, AKT1 and AKT2). An additional analysis was conducted comparing patients with DM prior to statin therapy and controls to determine whether the single nucleotide polymorphisms (SNPs) are specific to statin. Results: A total of 602 patients were analysed, including 71 (11.8%) with statin-induced NODM. After adjustment, IGF1R rs2715439, INSR rs1799817, INSR rs2059807 and PIK3R1 rs3730089 were found to be independently associated with NODM. In an additional analysis, all SNPs that demonstrated an association with statin-induced NODM lost their significance in patients with DM prior to statin therapy. Conclusion: This study revealed the ISP-related genetic effects, specifically involving genes such as INSR, IGF1R and PIK3R1, in the development of statin-induced NODM. Our findings suggest a potential mechanism of statin-induced NODM related to ISP-related genetic variants.
AB - Background: While statins are effective at managing lipid levels, there is growing evidence for new-onset diabetes mellitus (NODM). The insulin signalling pathway (ISP) inhibited by statins is one of the potential mechanisms; however, most studies have been limited to in vitro settings. Therefore, this study aimed to identify the genetic associations within the ISP-related genes and NODM. Methods: We performed a retrospective analysis of samples collected prospectively from February 2021 to May 2021. Among ISP-related genes, we selected 11 candidate genes (IGF1, IGF2, IGF1R, INSR, IRS1, IRS2, PIK3CA, PIK3CB, PIK3R1, AKT1 and AKT2). An additional analysis was conducted comparing patients with DM prior to statin therapy and controls to determine whether the single nucleotide polymorphisms (SNPs) are specific to statin. Results: A total of 602 patients were analysed, including 71 (11.8%) with statin-induced NODM. After adjustment, IGF1R rs2715439, INSR rs1799817, INSR rs2059807 and PIK3R1 rs3730089 were found to be independently associated with NODM. In an additional analysis, all SNPs that demonstrated an association with statin-induced NODM lost their significance in patients with DM prior to statin therapy. Conclusion: This study revealed the ISP-related genetic effects, specifically involving genes such as INSR, IGF1R and PIK3R1, in the development of statin-induced NODM. Our findings suggest a potential mechanism of statin-induced NODM related to ISP-related genetic variants.
KW - insulin receptor(s)
KW - insulin signalling
KW - insulin-like growth factors
KW - statins
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85210591354&partnerID=8YFLogxK
U2 - 10.1111/eci.14366
DO - 10.1111/eci.14366
M3 - Article
C2 - 39614667
AN - SCOPUS:85210591354
SN - 0014-2972
VL - 55
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
IS - 4
M1 - e14366
ER -
