Statins and risk of incident diabetes – is it a real clinical problem? Review article
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Published:
Mar 31, 2013
Keywords:
statins, diabetes, risk, prevention
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Abstract
Statins are widely used in cardiovascular prevention. Despite good tolerability statins are not free of side effects. One of the issue recently araised is new onset diabetes during statin treatment. Experimental studies have revealed potential mechanism responsible for hyperglycemia. Analyses of the clinical trials indicate that hyperglycemic and diabetogenic effect is not the same for each of the statin. Depending on the selection of the trials to meta-analyses relative risk of developing diabetes range from 1.03 up to 1.48. In this article we review literature of this topic.
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Pikto-Pietkiewicz , W., & Rawdanowicz , J. (2013). Statins and risk of incident diabetes – is it a real clinical problem?. Cardiology in Practice, 7(1), 4-12. Retrieved from https://journalsmededu.pl/index.php/kwp/article/view/1572
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2. Schachter M.: Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol. 2005; 19: 117-125.
3. Cybulska B., Kłosiewicz-Latoszek L.: Leki hipolipemizujące. W: Kardiologia. Podręcznik oparty na zasadach EBM. Tom 2. Szczeklik A., Tendera M. (red.). Medycyna Praktyczna, Kraków 2010: 1167-1168.
4. Jialal I., Stein D., Balis D., Grundy S.M., Adams-Huet B., Devaraj S.: Effect of hydroxymethylglutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001; 103(15): 1933-1935.
5. Park K.W., Hwang K.K., Cho H.J., Hur J., Yang H.M., Yoon C.H., Kang H.J., Oh B.H., Park Y.B., Kim H.S.: Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells inhypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Clin. Chim. Acta 2007; 388(1-2): 156-166.
6. Bruegel M., Teupser D., Haffner I., Mueller M., Thiery J.: Statins reduce macrophage inflammatory protein-1alpha expression in human activated monocytes. Clin. Exp. Pharmacol. Physiol. 2006; 33(12): 1144-1149.
7. Zeichner S., Mihos C.G., Santana O.: The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in malignancies: a comprehensive review. J. Cancer Res. Ther. 2012; 8(2): 176-183.
8. Dunne J.A., Bailey M.A., Griffin K.J., Sohrabi S., Coughlin P.A., Scott D.J.: Statins: The Holy Grail of Abdominal Aortic Aneurysm (AAA) Growth Attenuation? A Systematic Review of the Literature. Curr. Vasc. Pharmacol. 2012 [online].
9. Sadowitz B., Maier K.G., Gahtan V.: Basic science review: statin therapy – Part I: the pleiotropic effects of statins in cardiovascular disease. Vasc. Endovascular Surg. 2010; 44: 241-251.
10. Yada T., Nakata M., Shiraishi T. et al.: 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. 1999; 126: 1205-1213.
11. Ishikawa M., Okajima F., Inoue N. et al.: Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin secretion from a beta-cell line, MIN6 cells. J. Atheroscler. Thromb. 2006; 13: 329-335.
12. Sampson U.K., Linton M.F., Fazio S.: Are statins diabetogenic? Curr. Opin. Cardiol. 2011; 26(4): 342-7.
13. Donath M.Y., Boni-Schnetzler M., Ellingsgaard H., Ehses J.A.: Islet inflammation impairs the pancreatic beta-cell in type 2 diabetes. Physiology (Bethesda) 2009; 24: 325-331.
14. Kruit J.K., Kremer P.H., Dai L. et al.: Cholesterol efflux via ATP-binding cassette transporter A1(ABCA1) and cholesterol uptake via the LDL receptor influences cholesterol-induced impairment of beta cell function in mice. Experimental evidence that cellular cholesterol fluxes regulate insulin export by the β-cell. Diabetologia 2010; 53: 1110-1119.
15. Nakata M., Uto N., Maruyama I., Yada T.: Nitric oxide induces apoptosis via Ca2+-dependent processes in the pancreatic beta-cell line MIN6. Cell Struct. Funct. 1999; 24: 451-455.
16. Chamberlain L.H.: Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett. 2001; 507: 357-361.
17. Goldstein M.R., Mascitelli L.: Statin-induced diabetes: perhaps, it’s the tip of the iceberg. QJM 2011; 104(2): 174-178.
18. Goldfine A.B.: Statins: Is It Really Time to Reassess Benefits and Risks? N. Engl. J. Med. 2012; 366: 1752-1755.
19. Colbert J.D., Stone J.A.: Statin use and the risk of incident diabetes mellitus: a review of the literature. Can. J. Cardiol. 2012; 28(5): 581-589.
20. Sattar N., Preiss D., Murray H.M.: Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. The Lancet 2010; 375(9716): 735-742.
21. Scandinavian Simvastatin Survival Study group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.
22. de Lemos J.A., Blazing M.A., Wiviott S.D. et al.; A to Z Investigators: Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292(11): 1307-1316.
23. Downs J.R., Clearfield M., Weis S. et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615-1622.
24. Barzilay J.I., Davis B.R., Pressel S.L. et al.; ALLHAT Collaborative Research Group: Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study. Circ. Cardiovasc. Qual. Outcomes 2012; 5: 153-162.
25. Sever P.S., Dahlof B., Poulter N.R. et al.; ASCOT investigators: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicenter randomised controlled trial. Lancet 2003; 361: 1149-1158.
26. Kjekshus J., Apetrei E., Barrios V. et al.: Rosuvastatin in older patients with systolic heart failure. N. Engl. J. Med. 2007; 357: 2248-2261.
27. GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico): Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? Ital. Heart J. 2000; 1: 810-820.
28. Collins R., Armitage J., Parish S., Sleigh P., Peto R.; for the Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005-2016.
29. Pedersen T.R., Faergeman O., Kastelein J.J. et al.; Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group: Highdose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005; 294(19): 2437-2445.
30. Ridker P.M., Danielson E., Fonseca F.A.H. et al.: Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373: 1175-1182.
31. Keech A., Colquhoun D., Best J. et al.: Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose-results from the LIPID trial. Diabetes Care 2003; 26: 2713-2721.
32. Nakamura H., Arakawa K., Itakura H. et al.: Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006; 368: 1155-1163.
33. Shepherd J., Blauw G.J., Murphy M.B. et al.; PROSPER Study Group: Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623-1630.
34. Cannon C.P., Braunwald E., McCabe C.H. et al.; Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22 Investigators: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 2004; 350(15): 1495-1504.
35. Armitage J., Bowman L., Wallendszus K. et al.; Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group: Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010; 376(9753): 1658-1669.
36. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 2006; 355: 549-559.
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