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Pathogenesis and Management of the Diabetogenic Effect of Statins: a Role for Adiponectin and Coenzyme Q10?

  • Statin Drugs (BS Wiggins, Section Editor)
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Abstract

There is growing evidence to suggest that statin therapy is associated with an increased risk of incident diabetes. The risk for statin-related diabetes depends upon many factors including age, pre-existing diabetic risk, type and potency of statin. Several mechanisms have been suggested for the diabetogenic effects of statins involving processes that alter islet ß-cell function, resulting in impaired glucose metabolism. Recent evidence suggests that the association of statin therapy with the development of diabetes may be partly mediated by a statin-induced decrease in circulating adiponectin and coenzyme Q10. The available evidence suggests the benefit of statins in reducing cardiovascular events outweigh the risk of developing diabetes. Moreover, statin therapy does not impair glycemic control in diabetic patients. Expert recommendations for the use of statins in people at risk of developing diabetes have recently been published. However, further research is required to elucidate both the association between statin use and incident diabetes as well as underlying mechanisms.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major important

  1. International Diabetes Federation (IDF). IDF diabetes atlas. Epidemiology and morbidity. [http://www.idf.org/].

  2. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Supplement 1):S14–80.

    Google Scholar 

  3. Collins R, Armitage J, Parish S, Sleigh P, Peto R. 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.

    PubMed  Google Scholar 

  4. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S1–S45. Very recent guideline on the treatment of lipid disorders.

    PubMed  Google Scholar 

  5. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195. This study supports the notion that statin therapy increases the risk of incident diabetes.

    CAS  PubMed  Google Scholar 

  6. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42.

    CAS  PubMed  Google Scholar 

  7. Shah RV, Goldfine AB. Statins and risk of new-onset diabetes mellitus. Circulation. 2012;126:e282–e4.

    PubMed  Google Scholar 

  8. Sattar NA, Ginsberg H, Ray K, et al. The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice. Atheroscler Suppl. 2014;15:1–15. Very recent and comprehensive review on the diabetogenic effect of statin and guidance for clinical practice.

    PubMed  Google Scholar 

  9. Bell DS, Dinicolantonio J, O’Keefe J. Is statin-induced diabetes clinically relevant? A comprehensive review of the literature. Diabetes Obes Metab. 2014;16:689–94.

    CAS  PubMed  Google Scholar 

  10. Cholesterol Treatment Trialists’ (CTT) Collaborators. 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.

    Google Scholar 

  11. Ray KK, Seshasai SRK, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65 229 participants. Arch Intern Med. 2010;170:1024–31.

    CAS  PubMed  Google Scholar 

  12. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.

    PubMed  Google Scholar 

  13. Freeman DJ, Norrie J, Sattar N, et al. 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.

    CAS  PubMed  Google Scholar 

  14. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.

    CAS  PubMed  Google Scholar 

  15. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–57.

    Google Scholar 

  16. Sever PS, Dahlöf B, Poulter NR, et al. 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 tria. Lancet. 2003;361:1149–58.

    CAS  PubMed  Google Scholar 

  17. Waters DD, Ho JE, DeMicco DA, et al. 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.

    CAS  PubMed  Google Scholar 

  18. Collins R, Armitage J, Parish S, Sleight P, Peto R. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet. 2002;360:7–22.

    Google Scholar 

  19. 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. This study supports the notion that the absolute benefit of treatment outweighs the diabetic risk with statin therapy statin therapy increase the risk of incident diabetes.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Coleman CI, Reinhart K, Kluger J, White MC. The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2008;24:1359–62.

    PubMed  Google Scholar 

  22. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48:438–45.

    CAS  PubMed  Google Scholar 

  23. Preiss D, Seshasai SRK, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. JAMA. 2011;305:2556–64. A high impact meta-analysis showing that intense-dose statin therapy was associated with an increased risk of incident diabetes.

    CAS  PubMed  Google Scholar 

  24. Dormuth CR, Filion KB, Paterson JM, et al. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ. 2014;348:g3244.

    PubMed Central  PubMed  Google Scholar 

  25. 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. A population based cohort study with time to event analyses to estimate the relation between use of different statins and incident diabetes.

    PubMed Central  PubMed  Google Scholar 

  26. Masana L. Pitavastatin in cardiometabolic disease: therapeutic profile. Cardiovasc Diabetol. 2013;12 Suppl 1:S2.

    PubMed Central  PubMed  Google Scholar 

  27. Teramoto T. Pitavastatin: clinical effects from the LIVES study. Atheroscler Suppl. 2011;12:285–8.

    CAS  PubMed  Google Scholar 

  28. Kawai Y, Sato-Ishida R, Motoyama A, Kajinami K. Place of pitavastatin in the statin armamentarium: promising evidence for a role in diabetes mellitus. Drug Des Dev Ther. 2011;5:283–97.

    CAS  Google Scholar 

  29. Ishihara Y, Ohmori K, Mizukawa M, Ul Hasan A, Noma T, Kohno M. Beneficial direct adipotropic actions of pitavastatin in vitro and their manifestations in obese mice. Atherosclerosis. 2010;212:131–8.

    CAS  PubMed  Google Scholar 

  30. Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8:222–32.

    CAS  PubMed  Google Scholar 

  31. Fryirs M, Barter PJ, Rye K-A. Cholesterol metabolism and pancreatic β-cell function. Curr Opin Lipidol. 2009;20:159–64.

    CAS  PubMed  Google Scholar 

  32. Sampson UK, Linton MF, Fazio S. Are statins diabetogenic? Curr Opin Cardiol. 2011;26:342–7. A comprehensive review on the mechanisms of action by which statins increase the risk of developing diabetes.

    PubMed Central  PubMed  Google Scholar 

  33. Sattar N, Taskinen M-R. Statins are diabetogenic—myth or reality? Atheroscler Suppl. 2012;13:1–10.

    CAS  PubMed  Google Scholar 

  34. 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 β‐cells. Br J Pharmacol. 1999;126:1205–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Mcguire TF, Xu X-Q, Corey SJ, Romero GG, Sebti SM. Lovastatin disrupts early events in insulin signaling: a potential mechanism of lovastatins anti-mitogenic activity. Biochem Biophys Res Commun. 1994;204:399–406.

    CAS  PubMed  Google Scholar 

  36. Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett. 2001;507:357–61.

    CAS  PubMed  Google Scholar 

  37. 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.

    CAS  PubMed  Google Scholar 

  38. Hao M, Head WS, Gunawardana SC, Hasty AH, Piston DW. Direct effect of cholesterol on insulin secretion. A novel mechanism for pancreatic β-cell dysfunction. Diabetes. 2007;56(9):2328–38.

    CAS  PubMed  Google Scholar 

  39. Donath MY, Böni-Schnetzler M, Ellingsgaard H, Ehses JA. Islet inflammation impairs the pancreatic β-cell in type 2 diabetes. Physiology. 2009;24:325–31.

    CAS  PubMed  Google Scholar 

  40. Nakata M, Uto N, Maruyama I, Yada T. Nitric oxide induces apoptosis via Ca2+−dependent processes in the pancreatic β-cell line MIN6. Cell Struct Funct. 1999;24:451–5.

    CAS  PubMed  Google Scholar 

  41. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.

    CAS  PubMed  Google Scholar 

  42. Sirvent P, Fabre O, Bordenave S, et al. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins. Toxicol Appl Pharmacol. 2012;259:263–8.

    CAS  PubMed  Google Scholar 

  43. Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme a reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomized trials. Lancet. 2014. doi:10.1016/S0140-6736(14)61183-1.

    PubMed  Google Scholar 

  44. Frayling TM. Statins and type 2 diabetes: genetic studies on target. Lancet. 2014. doi:10.1016/S0140-6736(14)61639-1.

    Google Scholar 

  45. Takaguri A, Satoh K, Itagaki M, Tokumitsu Y, Ichihara K. Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes. J Pharmacol Sci. 2008;107:80–9.

    CAS  PubMed  Google Scholar 

  46. Koh KK, Quon MJ, Han SH, et al. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis. 2009;204:483–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Takagi T, Matsuda M, Abe M, et al. Effect of pravastatin on the development of diabetes and adiponectin production. Atherosclerosis. 2008;196:114–21.

    CAS  PubMed  Google Scholar 

  48. Frayn K, Karpe F, Fielding B, Macdonald I, Coppack S. Integrative physiology of human adipose tissue. Int J Obes. 2003;27:875–88.

    CAS  Google Scholar 

  49. Pittas AG, Joseph NA, Greenberg AS. Adipocytokines and insulin resistance. J Clin Endocrinol Metab. 2004;89:447–52.

    CAS  PubMed  Google Scholar 

  50. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004;24:29–33.

    CAS  PubMed  Google Scholar 

  51. Kishida K, Funahashi T, Shimomura I. Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin. Endocr Metab Immune Disord Drug Targets. 2012;12:118–31. A comprehensive review on the role of adiponectin in diabetes and atherosclerosis.

    CAS  PubMed  Google Scholar 

  52. Sattar N, Wannamethee G, Sarwar N, et al. Adiponectin and coronary heart disease. A prospective study and meta-analysis. Circulation. 2006;114:623–9.

    CAS  PubMed  Google Scholar 

  53. Wu Z, Cheng Y, Aung LHH, Li B. Association between adiponectin concentrations and cardiovascular disease in diabetic patients: a systematic review and meta-analysis. PLoS ONE. 2013;8:e78485.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Farvid M, Ng T, Chan D, Barrett P, Watts G. Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia. Diabetes Obes Metab. 2005;7:406–13.

    CAS  PubMed  Google Scholar 

  55. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:930–5.

    Google Scholar 

  56. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Gastr L Physiol. 2003;285:E527–33.

    CAS  Google Scholar 

  57. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302:179–88.

    CAS  PubMed  Google Scholar 

  58. Han L, Wu Q, Jiao M, et al. Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, −11377C>G, −11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetologia. 2011;54:2303–14.

    CAS  PubMed  Google Scholar 

  59. Dastani Z, Hivert M-F, Timpson N, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8:e1002607.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Mori Y, Otabe S, Dina C, et al. Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes. 2002;51:1247–55.

    CAS  PubMed  Google Scholar 

  61. Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7.

    CAS  PubMed  Google Scholar 

  62. Kim J-Y, van de Wall E, Laplante M, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117:2621–37.

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–6.

    CAS  PubMed  Google Scholar 

  64. Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes. 2002;51:1884–8.

    CAS  PubMed  Google Scholar 

  65. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116:1784–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Rabe K, Lehrke M, Parhofer KG, Broedl UC. Adipokines and insulin resistance. Mol Med. 2008;14:741–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Yoon MJ, Lee GY, Chung J-J, Ahn YH, Hong SH, Kim JB. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator–activated receptor α. Diabetes. 2006;55:2562–70.

    CAS  PubMed  Google Scholar 

  68. Okamoto M, Ohara-Imaizumi M, Kubota N, et al. Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration. Diabetologia. 2008;51:827–35.

    CAS  PubMed  Google Scholar 

  69. Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler MB. Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 2010;285:33623–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Qiao L, Kinney B, Yoo HS, Lee B, Schaack J, Shao J. Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1. Diabetes. 2012;61:1463–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Tsatsanis C, Zacharioudaki V, Androulidaki A, et al. Adiponectin induces TNF-α and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun. 2005;335:1254–63.

    CAS  PubMed  Google Scholar 

  72. Argiles J, Lopez-Soriano J, Lopez-Soriano F. Cytokines and diabetes: the final step? Involvement of TNF-alpha in both type I and II diabetes mellitus. Horm Metab Res. 1994;26:447–9.

    CAS  PubMed  Google Scholar 

  73. Miyagishima K, Hiramitsu S, Kato S, et al. Efficacy of atorvastatin therapy in ischaemic heart disease—effects on oxidized low-density lipoprotein and adiponectin. J Int Med Res. 2007;35:534–9.

    CAS  PubMed  Google Scholar 

  74. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol. 2005;45:1649–53.

    CAS  PubMed  Google Scholar 

  75. Anagnostis P, Selalmatzidou D, Polyzos SA, et al. Comparative effects of rosuvastatin and atorvastatin on glucose metabolism and adipokine levels in non-diabetic patients with dyslipidaemia: a prospective randomised open-label study. Int J Clin Pract. 2011;65:679–83.

    CAS  PubMed  Google Scholar 

  76. Thongtang N, Ai M, Otokozawa S, et al. Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation. Am J Cardiol. 2011;107:387–92.

    CAS  PubMed  Google Scholar 

  77. Koh KK, Quon MJ, Han SH, et al. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes Care. 2008;31:776–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Forst T, Pfützner A, Lübben G, et al. Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT study. Metabolism. 2007;56:491–6.

    CAS  PubMed  Google Scholar 

  79. Devaraj S, Siegel D, Jialal I. Simvastatin (40 mg/day), adiponectin levels, and insulin sensitivity in subjects with the metabolic syndrome. Am J Cardiol. 2007;100:1397–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Sonmez A, Dogru T, Tasci I, et al. The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia. Clin Endocrinol (Oxf). 2006;64:567–72.

    CAS  Google Scholar 

  81. Sugiyama S, Fukushima H, Kugiyama K, et al. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis. 2007;194:e43–51.

    CAS  PubMed  Google Scholar 

  82. Yokoyama H, Saito S, Daitoku K, et al. Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease. Fundam Clin Pharmacol. 2011;25:378–87.

    CAS  PubMed  Google Scholar 

  83. Qu HY, Xiao YW, Jiang GH, Wang ZY, Zhang Y, Zhang M. Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. Pharm Res. 2009;26:958–64.

    CAS  PubMed  Google Scholar 

  84. Kim W, Hong MJ, Woo JS, Kang WY, Hwang SH, Kim W. Rosuvastatin does not affect fasting glucose, insulin resistance, or adiponectin in patients with mild to moderate hypertension. Chonnam Med J. 2013;49:31–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  85. 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.

    CAS  PubMed  Google Scholar 

  86. Kostapanos M, Milionis H, Agouridis AD, Rizos C, Elisaf M. Rosuvastatin treatment is associated with an increase in insulin resistance in hyperlipidaemic patients with impaired fasting glucose. Int J Clin Pract. 2009;63:1308–13.

    CAS  PubMed  Google Scholar 

  87. Mita T, Nakayama S, Abe H, et al. Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia. J Diabetes Investig. 2013;4:297–303.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Nomura S, Taniura T, Shouzu A, et al. Effects of pitavastatin on plasminogen activator inhibitor-1 in hyperlipidemic patients. Int J Gen Med. 2012;5:535–40.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Inami N, Nomura S, Shouzu A, et al. Effects of pitavastatin on adiponectin in patients with hyperlipidemia. Pathophysiol Haemost Thromb. 2007;36:1–8.

    CAS  PubMed  Google Scholar 

  90. Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37:31–7.

    CAS  PubMed  Google Scholar 

  91. Chew G, Watts G. Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the ‘recoupling hypothesis’. QJM. 2004;97:537–48.

    CAS  PubMed  Google Scholar 

  92. Molyneux SL, Young JM, Florkowski CM, Lever M, George PM. Coenzyme Q10: is there a clinical role and a case for measurement? Clin Biochem Rev. 2008;29:71–82.

    PubMed Central  PubMed  Google Scholar 

  93. Ates O, Bilen H, Keles S, et al. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy. Int J Ophthalmol. 2013;6:675–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. McCarty M. Can correction of sub-optimal coenzyme Q status improve b-cell function in type II diabetics? Med Hypotheses. 1999;52:397–400.

    CAS  PubMed  Google Scholar 

  95. Littarru GP, Langsjoen P. Coenzyme Q10 and statins: biochemical and clinical implications. Mitochondrion. 2007;7:S168–74.

    CAS  PubMed  Google Scholar 

  96. Stocker R, Pollicino C, Gay CA, et al. Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: a prospective case–control study from the LIPID study. Atherosclerosis. 2006;187:198–204.

    CAS  PubMed  Google Scholar 

  97. Mabuchi H, Higashikata T, Kawashiri M, et al. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb. 2005;12:111–9.

    CAS  PubMed  Google Scholar 

  98. Maechler P, Li N, Casimir M, Vetterli L, Frigerio F, Brun T. Role of mitochondria in β-cell function and dysfunction. Adv Exp Med Biol. 2010;654:193–216.

    CAS  PubMed  Google Scholar 

  99. Draeger A, Monastyrskaya K, Mohaupt M, et al. Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. J Physiol. 2006;210:94–102.

    CAS  Google Scholar 

  100. Khamseh ME, Malek M, Aghili R, Emami Z. Sarcopenia and diabetes: pathogenesis and consequences. Br J Diabetes Vasc Dis. 2011;11:230–4.

    Google Scholar 

  101. Hodgson J, Watts G, Playford D, Burke V, Croft K. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002;56:1137–42.

    CAS  PubMed  Google Scholar 

  102. Shimura Y, Hogimoto S. Significance of coenzyme Q10 on the treatment of diabetes mellitus. Jpn J Clin Exp Med. 1981;58:1349–52.

    Google Scholar 

  103. Singh R, Niaz M, Rastogi S, Shukla P, Thakur A. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. 1999;13:203–8.

    CAS  PubMed  Google Scholar 

  104. Schroeder MM, Belloto Jr RJ, Hudson RA, McInerney MF. Effects of antioxidants coenzyme Q10 and lipoic acid on interleukin-1β-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets. Immunopharmacol Immunotoxicol. 2005;27:109–22.

    CAS  PubMed  Google Scholar 

  105. Amin MM, Asaad GF, Salam RMA, El-Abhar HS, Arbid MS. Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats. PLoS ONE. 2014;9:e89169.

    PubMed Central  PubMed  Google Scholar 

  106. Ganesan S, Ito MK. Coenzyme Q10 ameliorates the reduction in GLUT4 transporter expression induced by simvastatin in 3T3-L1 adipocytes. Metab Syndr Relat Disord. 2013;11:251–5.

    CAS  PubMed  Google Scholar 

  107. Zhou Y, Yuan Y, Cai R-R, et al. Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis. Expert Opin Pharmacother. 2013;14:1575–84.

    CAS  PubMed  Google Scholar 

  108. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–818.

    PubMed  Google Scholar 

  109. Rydén L, Grant PJ, Anker SD, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013;34:3035–87. A recent guideline on the management of diabetes, pre-diabetes and cardiovascular disease.

    PubMed  Google Scholar 

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Conflict of Interest

Dick C. Chan, Jing Pang and Gerald F. Watts declare that they have no conflict of interest.

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Authors and Affiliations

  1. Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

    Dick C. Chan, Jing Pang & Gerald F. Watts

  2. Cardiometabolic Medicine, Royal Perth Hospital, Perth, Western Australia, Australia

    Gerald F. Watts

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  1. Dick C. Chan
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  2. Jing Pang
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  3. Gerald F. Watts
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Corresponding author

Correspondence to Gerald F. Watts.

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This article is part of the Topical Collection on Statin Drugs

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Chan, D.C., Pang, J. & Watts, G.F. Pathogenesis and Management of the Diabetogenic Effect of Statins: a Role for Adiponectin and Coenzyme Q10?. Curr Atheroscler Rep 17, 472 (2015). https://doi.org/10.1007/s11883-014-0472-7

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  • DOI: https://doi.org/10.1007/s11883-014-0472-7

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