Diabetogenic effect of statins: A double-edged sword?

Diabetes and Metabolism Journal

Volumn 37, Issue 6, 2013, Pages 415-422

  Yoon, Ji Sung ^a   Lee, Hyoung Woo ^a  

^a Yeungnam University College of Medicine   (South Korea)

Author keywords

Cardiovascular diseases; Diabetes; Statins

Indexed keywords

ATORVASTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN;

CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DIABETOGENESIS; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG SAFETY; HUMAN; HYPERLIPIDEMIA; NONHUMAN; PATHOPHYSIOLOGY; PATIENT IDENTIFICATION; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; TREATMENT OUTCOME;

EID: 84892187236     PISSN: 22336079     EISSN: 22336087     Source Type: Journal    
DOI: 10.4093/dmj.2013.37.6.415     Document Type: Review

References (42)

1. Gotto AM Jr, Moon JE. Management of cardiovascular risk: the importance of meeting lipid targets. Am J Cardiol 2012;110(1 Suppl):3A-14A.
2. Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks. Curr Opin Cardiol 2013;28:554-60.
3. Metz SA, Rabaglia ME, Stock JB, Kowluru A. Modulation of insulin secretion from normal rat islets by inhibitors of the post-translational modifications of GTP-binding proteins. Biochem J 1993;295(Pt 1):31-40.
4. Ohrvall M, Lithell H, Johansson J, Vessby B. A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia. Metabolism 1995;44:212-7.
5. Mills EJ, Wu P, Chong G, Ghement I, Singh S, Akl EA, Eyawo O, Guyatt G, Berwanger O, Briel M. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM 2011;104:109-24.
6. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 2009;32:1924-9.
7. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-42.
8. Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011;305:2556-64.
9. Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001;103:357-62.
10. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
11. U.S. Food and Drug Administration: FDA drug safety communication: important safety label changes to cholesterol lowering statin drugs. Available from: http://www.fda.gov/drugs/drugsafety/ucm293101.htm (update 2012 Feb 28).
12. Collins R, Armitage J, Parish S, Sleigh P, Peto R; 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;361:2005-16.
13. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; 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 multicentre randomised controlled trial. Drugs 2004;64 Suppl 2:43-60.
14. Keech A, Colquhoun D, Best J, Kirby A, Simes RJ, Hunt D, Hague W, Beller E, Arulchelvam M, Baker J, Tonkin A; LIPID Study Group. 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;26:2713-21.
15. Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamenskỳ G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248-61.
16. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 2012;380:565-71.
17. Preiss D, Sattar N. Pharmacotherapy: statins and new-onset diabetes: the important questions. Nat Rev Cardiol 2012;9:190-2.
18. Waters DD, Ho JE, DeMicco DA, Breazna A, Arsenault BJ, Wun CC, Kastelein JJ, Colhoun H, Barter P. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol 2011;57:1535-45.
19. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol 2007;99:410-4.
20. Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, Manson JE, Qiao Y, Liu S, Merriam PA, Rahilly-Tierny C, Thomas F, Berger JS, Ockene JK, Curb JD, Ma Y. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 2012;172:144-52.
21. Guclu F, Ozmen B, Hekimsoy Z, Kirmaz C. Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome. Biomed Pharmacother 2004;58:614-8.
22. Koh KK, Sakuma I, Quon MJ. Differential metabolic effects of distinct statins. Atherosclerosis 2011;215:1-8.
23. Sugiyama S, Fukushima H, Kugiyama K, Maruyoshi H, Kojima S, Funahashi T, Sakamoto T, Horibata Y, Watanabe K, Koga H, Sugamura K, Otsuka F, Shimomura I, Ogawa H. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis 2007;194:e43-51.
24. Takagi T, Matsuda M, Abe M, Kobayashi H, Fukuhara A, Komuro R, Kihara S, Caslake MJ, McMahon A, Shepherd J, Funahashi T, Shimomura I. Effect of pravastatin on the development of diabetes and adiponectin production. Atherosclerosis 2008;196:114-21.
25. Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract 2010;87:98-107.
26. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ 2013;346:f2610.
27. Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-25.
28. American Diabetes Association. Standards of medical care in diabetes: 2011. Diabetes Care 2011;34(Suppl 1):S11-61.
29. Goldstein MR, Mascitelli L. Do statins cause diabetes? Curr Diab Rep 2013;13:381-90.
30. Sampson UK, Linton MF, Fazio S. Are statins diabetogenic? Curr Opin Cardiol 2011;26:342-7.
31. Sattar N, Taskinen MR. Statins are diabetogenic: myth or reality? Atheroscler Suppl 2012;13:1-10.
32. Yada T, Nakata M, Shiraishi T, Kakei M. 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;126:1205-13.
33. Xia F, Xie L, Mihic A, Gao X, Chen Y, Gaisano HY, Tsushima RG. Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic beta-cells. Endocrinology 2008;149:5136-45.
34. Hao M, Head WS, Gunawardana SC, Hasty AH, Piston DW. Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction. Diabetes 2007;56:2328-38.
35. Mabuchi H, Higashikata T, Kawashiri M, Katsuda S, Mizuno M, Nohara A, Inazu A, Koizumi J, Kobayashi J. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb 2005;12:111-9.
36. Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev 2012;40:188-94.
37. Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner J 2010;10:16-21.
38. Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia 2006;49:1881-92.
39. Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett 2001;507:357-61.
40. 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;24:451-5.
41. Draeger A, Monastyrskaya K, Mohaupt M, Hoppeler H, Savolainen H, Allemann C, Babiychuk EB. Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. J Pathol 2006;210:94-102.
42. Khamseh ME, Malek M, Aghili R, Emami Z. Sarcopenia and diabetes: pathogenesis and consequences. Br J Diabetes Vasc Dis 2011;11:230-4.