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To the Editor: In a recent issue of Diabetologia, Cederberg et al report a dose-dependent increased risk of type 2 diabetes with long-term simvastatin or atorvastatin treatment [1]. Impaired insulin sensitivity and reduced pancreatic insulin secretion may mediate this diabetogenic effect [1]. Some comments may be of interest.
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1.
Dose-response and 3-hydroxy-3-methylglutaryl-CoA reductase inhibition We previously showed that rosuvastatin increased insulin resistance in patients with impaired fasting glucose in a dose-dependent manner [2]. It was suggested that statins reduce insulin sensitivity in parallel with their 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitory capacity [3]. This effect might be most prominent for the potent statin rosuvastatin.
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2.
Lipophilic vs hydrophilic statins Impaired insulin secretion induced by the lipophilic simvastatin and atorvastatin may not be relevant for the hydrophilic rosuvastatin [3, 4]. Post-treatment changes in HOMA of beta cell function (HOMA-B) [5] as a surrogate of pancreatic beta cell function were calculated using insulin and glucose values from a previous dataset of rosuvastatin-treated patients [2]. Rosuvastatin at daily doses of 10, 20 and 40 mg dose-dependently increased HOMA-B by 14.2% (p = not significant vs baseline), 25.4% (p < 0.05 vs baseline; p < 0.05 vs 10 mg) and 46.1% (p < 0.05 vs baseline; p < 0.05 vs 10 and 20 mg), respectively. The resultant compensatory hyperinsulinaemia may prevent hyperglycaemia in the short-term [2]. In this context, it is relevant to prospectively compare the time-dependent diabetogenic effects of lipophilic and hydrophilic statins.
Abbreviations
- HOMA-B:
-
HOMA of beta cell function
References
Cederberg H, Stančáková A, Yaluri N, Modi S, Kuusisto J, Laakso M (2015) Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia 58:1109–1117
Kostapanos MS, Milionis HJ, Agouridis AD, Rizos CV, Elisaf MS (2009) Rosuvastatin treatment is associated with an increase in insulin resistance in hyperlipidaemic patients with impaired fasting glucose. Int J Clin Pract 63:1308–1313
Kostapanos MS, Liamis GL, Milionis HJ, Elisaf MS (2010) Do statins beneficially or adversely affect glucose homeostasis? Curr Vasc Pharmacol 8:612–631
Yada T, Nakata M, Shiraishi T, Kakei M (1999) Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells. Br J Pharmacol 126:1205–1213
Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S (2007) Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: the Women’s Health Initiative Observational Study. Diabetes Care 30:1747–1752
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MSE has given talks, attended conferences and participated in trials sponsored by AstraZeneca. MSK receives a fee for his physician role at the GlaxoSmithKline (GSK) Clinical Trials Unit in Cambridge, UK. The authors declare that this does not constitute a duality of interest for this manuscript.
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Kostapanos, M.S., Agouridis, A.P. & Elisaf, M.S. Variable effects of statins on glucose homeostasis parameters and their diabetogenic role. Diabetologia 58, 1960–1961 (2015). https://doi.org/10.1007/s00125-015-3633-5
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DOI: https://doi.org/10.1007/s00125-015-3633-5