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Association between insulin-associated gene polymorphisms and new-onset diabetes mellitus in statin-treated patients

Minju Park1, Jung Sun Kim1, Yoon-A Park1

  • 1College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.

European Journal of Clinical Investigation
|November 30, 2024
PubMed
Abstract

Insights

Statins can increase diabetes risk by affecting the insulin signaling pathway (ISP). Genetic variations in ISP-related genes like INSR, IGF1R, and PIK3R1 are linked to statin-induced new-onset diabetes mellitus (NODM).

Area of Science:

  • Genetics
  • Endocrinology
  • Pharmacology

Background:

  • Statins effectively manage lipid levels but are associated with new-onset diabetes mellitus (NODM).
  • The insulin signaling pathway (ISP) is a potential mechanism, but most research is in vitro.
  • This study investigates genetic associations within ISP-related genes and NODM.

Purpose of the Study:

  • To identify genetic associations within ISP-related genes and statin-induced NODM.
  • To explore the role of specific single nucleotide polymorphisms (SNPs) in the ISP.
  • To differentiate between general diabetes risk and statin-specific effects.

Main Methods:

  • Retrospective analysis of prospectively collected samples (February-May 2021).
  • Selection of 11 candidate ISP-related genes (IGF1, IGF2, IGF1R, INSR, IRS1, IRS2, PIK3CA, PIK3CB, PIK3R1, AKT1, AKT2).
  • Analysis of SNPs and comparison with patients having pre-existing diabetes.

Main Results:

  • 602 patients analyzed; 11.8% developed statin-induced NODM.
  • Four SNPs (IGF1R rs2715439, INSR rs1799817, INSR rs2059807, PIK3R1 rs3730089) were independently associated with NODM.
  • Associated SNPs lost significance in patients with pre-existing diabetes, suggesting statin specificity.

Conclusions:

  • ISP-related genetic variants, particularly in INSR, IGF1R, and PIK3R1, are implicated in statin-induced NODM.
  • Findings suggest a potential mechanism for statin-induced NODM involving ISP genetic variations.
  • Genetic predisposition may influence the risk of developing diabetes while on statin therapy.
Keywords:
insulin receptor(s)insulin signallinginsulin‐like growth factorsstatinstype 2 diabetes

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