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Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin.

Abstract

Statins represent the elective lipid-lowering strategy in hyperlipidemic and high cardiovascular-risk patients. Despite excellent safety and tolerability, reversible muscle-related and dose-dependent adverse events may decrease a patient's compliance. Large meta-analyses, post-hoc and genetic studies showed that statins might increase the risk of new-onset diabetes (NOD), particularly in insulin-resistant, obese, old patients. Race, gender, concomitant medication, dose and treatment duration may also contribute to this effect. Based on this evidence, to warn against the possibility of statin-induced NOD or worsening glycemic control in patients with already established diabetes, FDA and EMA changed the labels of all the available statins in the USA and Europe. Recent meta-analyses and retrospective studies demonstrated that statins' diabetogenicity is a dose-related class effect, but the mechanism(s) is not understood. Among statins, only pravastatin and pitavastatin do not deteriorate glycemic parameters in patients with and without type 2 diabetes mellitus. Interestingly, available data, obtained in small-scale, retrospective or single-center clinical studies, document that pitavastatin, while ameliorating lipid profile, seems protective against NOD. Beyond differences in pharmacokinetics between pitavastatin and the other statins (higher oral bioavailability, lower hepatic uptake), its consistent increases in plasma adiponectin documented in clinical studies may be causally connected with its effect on glucose metabolism. Adiponectin is a protein with antiatherosclerotic, anti-inflammatory and antidiabetogenic properties exerted on liver, skeletal muscle, adipose tissue and pancreatic beta cells. Further studies are required to confirm this unique property of pitavastatin and to understand the mechanism(s) leading to this effect.

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  • Authors+Show Affiliations

    ,

    Dipartimento di Scienze Farmacologiche e Biomolecolari (DISFeB), Università degli Studi di Milano, Via Balzaretti, 9, 20133 Milano, Italy. Electronic address: lorenzo.arnaboldi@unimi.it.

    Dipartimento di Scienze Farmacologiche e Biomolecolari (DISFeB), Università degli Studi di Milano, Via Balzaretti, 9, 20133 Milano, Italy; IRCCS Multimedica, Milano, Italy. Electronic address: alberto.corsini@unimi.it.

    Source

    Atherosclerosis. Supplements 16: 2015 Jan pg 1-27

    MeSH

    Adiponectin
    Animals
    Biomarkers
    Blood Glucose
    Diabetes Mellitus, Type 2
    Dyslipidemias
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Protective Factors
    Quinolines
    Risk Assessment
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    25575403

    Citation

    Arnaboldi, Lorenzo, and Alberto Corsini. "Could Changes in Adiponectin Drive the Effect of Statins On the Risk of New-onset Diabetes? the Case of Pitavastatin." Atherosclerosis. Supplements, vol. 16, 2015, pp. 1-27.
    Arnaboldi L, Corsini A. Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atheroscler Suppl. 2015;16:1-27.
    Arnaboldi, L., & Corsini, A. (2015). Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atherosclerosis. Supplements, 16, pp. 1-27. doi:10.1016/S1567-5688(14)70002-9.
    Arnaboldi L, Corsini A. Could Changes in Adiponectin Drive the Effect of Statins On the Risk of New-onset Diabetes? the Case of Pitavastatin. Atheroscler Suppl. 2015;16:1-27. PubMed PMID: 25575403.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. AU - Arnaboldi,Lorenzo, AU - Corsini,Alberto, PY - 2015/1/11/entrez PY - 2015/1/13/pubmed PY - 2015/9/17/medline KW - Adiponectin KW - Insulin sensitivity KW - Pitavastatin KW - Statins KW - Type 2 diabetes mellitus (T2DM) SP - 1 EP - 27 JF - Atherosclerosis. Supplements JO - Atheroscler Suppl VL - 16 N2 - Statins represent the elective lipid-lowering strategy in hyperlipidemic and high cardiovascular-risk patients. Despite excellent safety and tolerability, reversible muscle-related and dose-dependent adverse events may decrease a patient's compliance. Large meta-analyses, post-hoc and genetic studies showed that statins might increase the risk of new-onset diabetes (NOD), particularly in insulin-resistant, obese, old patients. Race, gender, concomitant medication, dose and treatment duration may also contribute to this effect. Based on this evidence, to warn against the possibility of statin-induced NOD or worsening glycemic control in patients with already established diabetes, FDA and EMA changed the labels of all the available statins in the USA and Europe. Recent meta-analyses and retrospective studies demonstrated that statins' diabetogenicity is a dose-related class effect, but the mechanism(s) is not understood. Among statins, only pravastatin and pitavastatin do not deteriorate glycemic parameters in patients with and without type 2 diabetes mellitus. Interestingly, available data, obtained in small-scale, retrospective or single-center clinical studies, document that pitavastatin, while ameliorating lipid profile, seems protective against NOD. Beyond differences in pharmacokinetics between pitavastatin and the other statins (higher oral bioavailability, lower hepatic uptake), its consistent increases in plasma adiponectin documented in clinical studies may be causally connected with its effect on glucose metabolism. Adiponectin is a protein with antiatherosclerotic, anti-inflammatory and antidiabetogenic properties exerted on liver, skeletal muscle, adipose tissue and pancreatic beta cells. Further studies are required to confirm this unique property of pitavastatin and to understand the mechanism(s) leading to this effect. SN - 1878-5050 UR - https://www.unboundmedicine.com/medline/citation/25575403/Could_changes_in_adiponectin_drive_the_effect_of_statins_on_the_risk_of_new_onset_diabetes_The_case_of_pitavastatin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5688(14)70002-9 DB - PRIME DP - Unbound Medicine ER -