Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights
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Date
2020-07-02Author
Galicia García, Unai
Jebari Benslaiman, Shifa
Larrea Sebal, Asier
Belloso Uribe, Kepa
Siddiqi, Haziq
Ostolaza Echabe, Elena Amaya
Benito Vicente, Asier
Martín Plágaro, César Augusto
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International Journal of Molecular Sciences 21(13) : (2020) // Article ID 4725
Abstract
Statins are the gold-standard treatment for the prevention of primary and secondary cardiovascular disease, which is the leading cause of mortality worldwide. Despite the safety and relative tolerability of statins, observational studies, clinical trials and meta-analyses indicate an increased risk of developing new-onset type 2 diabetes mellitus (T2DM) after long-term statin treatment. It has been shown that statins can impair insulin sensitivity and secretion by pancreatic β-cells and increase insulin resistance in peripheral tissues. The mechanisms involved in these processes include, among others, impaired Ca2+ signaling in pancreatic β-cells, down-regulation of GLUT-4 in adipocytes and compromised insulin signaling. In addition, it has also been described that statins’ impact on epigenetics may also contribute to statin-induced T2DM via differential expression of microRNAs. This review focuses on the evidence and mechanisms by which statin therapy is associated with the development of T2DM. This review describes the multifactorial combination of effects that most likely contributes to the diabetogenic effects of statins. Clinically, these findings should encourage clinicians to consider diabetes monitoring in patients receiving statin therapy in order to ensure early diagnosis and appropriate management.
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Except where otherwise noted, this item's license is described as 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).