Statin therapy and new-onset diabetes: Molecular mechanisms and clinical relevance

Current Pharmaceutical Design

Volumn 19, Issue 27, 2013, Pages 4904-4912

  Banach, Maciej ^a   Malodobra Mazur, Malgorzata ^b   Gluba, Anna ^a   Katsiki, Niki ^c   Rysz, Jacek ^a   Dobrzyn, Agnieszka ^b  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

^b NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY   (Poland)

^c ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

Author keywords

Insulin resistance; Lipids; New onset diabetes mellitus; Statins; Therapy

Indexed keywords

ADIPOCYTOKINE; ATORVASTATIN; COLESEVELAM; EZETIMIBE; FIBRIC ACID DERIVATIVE; FLUINDOSTATIN; GLUCOSE; GLUCOSE TRANSPORTER 4; HEMOGLOBIN A1C; INSULIN; INSULIN RECEPTOR; LOW DENSITY LIPOPROTEIN; MEVINOLIN; NICOTINIC ACID; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN;

ADIPOCYTE; ARTICLE; AUTOPHOSPHORYLATION; CYTOKINE RELEASE; DIABETES MELLITUS; DIABETIC HYPERTENSION; DYSLIPIDEMIA; GLUCOSE BLOOD LEVEL; GLUCOSE TRANSPORT; HEMOGLOBIN BLOOD LEVEL; HIGH RISK POPULATION; HUMAN; INSULIN RELEASE; INSULIN SENSITIVITY; LIPID BLOOD LEVEL; META ANALYSIS (TOPIC); NEW ONSET DIABETES; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION;

ADIPOCYTES; ADIPOKINES; ANIMALS; DIABETES MELLITUS, TYPE 2; DYSLIPIDEMIAS; EVIDENCE-BASED MEDICINE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN-SECRETING CELLS; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION;

EID: 84881329514     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319270014     Document Type: Article

References (91)

1. Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (London) 2005, 2: 5.
2. Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Dyslipidaemia of obesity, metabolic syndrome and type 2 diabetes mellitus: the case for residual risk reduction after statin treatment. Open Cardiovasc Med J 2011; 5: 24-34.
3. Mikhailidis DP, Elisaf M, Rizzo M, et al. "European panel on low density lipoprotein (LDL) subclasses": a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses: executive summary. Curr Vasc Pharmacol 2011; 9: 531-2.
4. Mikhailidis DP, Elisaf M, Rizzo M, et al. "European panel on low density lipoprotein (LDL) subclasses": a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses. Curr Vasc Pharmacol 2011; 9: 533-71.
5. Bergman RN, Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 2000; 11: 351-6.
6. Hsueh WA, Law R. The central role of fat and effect of peroxisome proliferator-activated receptor-gamma on progression of insulin resistance and cardiovascular disease. Am J Cardiol 2003; 92(4A): 3J-9J.
7. Wong V, Stavar L, Szeto L, et al. Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. Atherosclerosis 2006; 184: 348-55.
8. Zoungas S, Patel A. Cardiovascular outcomes in type 2 diabetes: the impact of preventative therapies. Ann N Y Acad Sci 2010; 1212: 29-40.
9. Lewis SJ. Lipid-lowering therapy: who can benefit? Vasc Health Risk Manag 2011; 7: 525-34.
10. Sukhija R, Prayaga S, Marashdeh M, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med 2009; 57: 495-9
11. 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: 2195-207.
12. 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.
13. Kohanski RA. Insulin receptor autophosphorylation. I. Autophosphorylation kinetics of the native receptor and its cytoplasmic kinase domain. Biochemistry 1993; 32: 5766-72.
14. Boura-Halfon S, Zick Y. Phosphorylation of IRS protein, insulin action and insulin resistance. Am J Physiol Endocrinol Metab 2009; 296: 581-91.
15. Hawkins PT, Anderson KE, Davidson K, Stephens LR. Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans 2006; 34: 647-662.
16. Pilch RF. The mass action hypothesis: formation of Glut4 storage vesicles, a tissue-specific, regulated exocytic compartment. Acta Physiol 2008; 192: 89-101.
17. Mäuser W, Perwitz N, Meier B, Fasshauer M, Klein J. Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake. Eur J Pharmacol 2007; 564: 37-46.
18. McGuire TF, Xu XQ, Corey SJ, Romero GG, Sebti SM. Lovastatin disrupts early events in insulin signaling: a potential mechanism of lovastatin's anti-mitogenic activity. Biochem Biophys Res Commun 1994; 204: 399-406.
19. 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.
20. Pylypenko O, Goud B. Posttranslational modifications of Rab GTPases help their insertion into membranes. Proc Natl Acad Sci U S A 2012; 109: 5555-6.
21. Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett 2001; 507: 357-61.
22. Koh KK, Sakuma I, Quon M J. Differential metabolic effects of distinct statins. Atherosclerosis 2011; 215: 1-8.
23. Lalli CA, Pauli JR, Prada PO, et al. Statin modulates insulin signaling and insulin resistance in liver and muscle of rats fed a high-fat diet. Metabolism. 2008; 57: 57-65.
24. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305: 2556-64.
25. Wanders D, Plaisance EP, Judd RL. Pharmacological effects of lipid-lowering drugs on circulating adipokines. World J Diabetes 2010; 1: 116-28.
26. Lang J. Molecular mechanism and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem 1999; 259: 3-17.
27. Newsholme P, Haber EP, Hirabara SM, et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and nonmitochondrial ROS production and activity. J Physiol 2007; 583: 9-24.
28. Ma ZA, Zhao Z, Turk J. Mitochondrial dysfunction and-cell failure in type 2 diabetes mellitus. Exp Diabetes Res 2012; 2012: 703538.
29. Papa S, Martino PL, Capitanio G, et al. The oxidative phosphorylation system in mammalian mitochondria. Adv Exp Med Biol 2012; 942: 3-37.
30. Quinzii CM, DiMauro S, Hirano M. Human Coenzyme Q10 deficiency. Neurochem Res 2007; 32: 723-7.
31. 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.
32. Chu CS, Kou HS, Lee CJ, Lee KT, Chen SH, et al. Effect of atorvastatin withdrawal on circulating coenzyme Q10 concentration in patients with hypercholesterolemia. Biofactors 2006; 28: 177-84.
33. Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol 2004; 61: 889-92.
34. Ishikawa M, Okajima F, Inoue N, et al. Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin secretion from a betacell line, MIN6 cells. J Atheroscler Thromb 2006; 13: 329-35.
35. Metz SA, Rabaglia ME, Stock JB, Kowluru A. Modulation of insulin secretion from normal rat islets by inhibitors of the posttranslational modifications of GTP-binding proteins. Biochem J 1993; 295: 31-40.
36. Amin R, Chen HQ, Tannous M, Gibbs R, Kowluru A. Inhibition of glucose-and calcium-induced insulin secretion from betaTC3 cells by novel inhibitors of protein isoprenylation. J Pharmacol Exp Ther 2002; 303: 82-8.
37. 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.
38. Xia F, Xie L, Mihic A, et al. Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic beta-cells. Endocrinology 2008; 149: 5136-45.
39. Mita T, Watada H, Nakayama S, et al. Preferable effect of pravastatin compared to atorvastatin on beta cell function in Japanese early-state type 2 diabetes with hypercholesterolemia. Endocr J 2007; 54: 441-7
40. Abe M, Toyohara T, Ishii A, et al. The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides. Drug Metab Pharmacokinet 2010; 25: 274-82.
41. Koh KK, Quon MJ, Sakuma I, et al. Differential metabolic effects of rosuvastatin and pravastatin in hypercholesterolemic patients. Int J Cardiol. 2011 Dec 26. doi: 10.1016/j.ijcard.2011.11.028
42. Stpie M, Wlazé RN, Paradowski M, et al. Serum concentrations of adiponectin, leptin, resistin, ghrelin and insulin and their association with obesity indices in obese normo-and hypertensive patients-pilot study. Arch Med Sci 2012; 8: 431-6.
43. Kolovou GD, Anagnostopoulou KK, Cokkinos DV. Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med J 2005; 81: 358-66.
44. Annuzzi G, Bozzetto L, Patti L, et al. Type 2 diabetes mellitus is characterized by reduced postprandial adiponectin response: a possible link with diabetic postprandial dyslipidemia. Metabolism 2010; 59: 567-74.
45. Mojiminiyi OA, Abdella NA, Al Arouj M, Nakhi B. Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patient with type 2 diabetes. Int J Obes 2007; 31: 213-20.
46. Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50: 1126-33.
47. Statnick MA, Beavers LS, Conner LJ, et al. Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 2000; 1: 81-8.
48. Koh KK, Quon MJ, Sakuma I, et al. Effects of simvastatin therapy on circulating adipocytokines in patients with hypercholesterolemia. Int J Cardiol 2011; 146: 434-7.
49. Bogan J S, Lodish H F. Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4. J Cell Biol 1999; 146: 609-20.
50. Yokoyama H, Saito S, Daitoku K, et al. Okumura K. 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.
51. Tsutamoto T, Yamaji M, Kawahara C, et al. Effect of simvastatin vs. rosuvastatin on adiponectin and haemoglobin A1c levels in patients with non-ischaemic chronic heart failure. Eur J Heart Fail 2009; 11: 1195-201.
52. 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.
53. Su Y-M, Li J, Luan Y, Wang L-F. Effect of statins therapy on leptin levels in patients with coronary heart disease. Peptides 2010; 31, 1205-7.
54. Aabuzek K, Budak A, Budak-Duawa A, et al. Atorvastatin and fenofibric acid differentially affect the release of adipokines in the visceral and subcutaneous cultures of adipocytes that were obtained from patients with and without mixed dyslipidemia. Pharmacol Reports 2011; 63, 1124-36.
55. Szotowska M, Czerwienska B, Adamczak M, Chudek J, Wiecek A. Effect of low-dose atorvastatin on plasma concentrations of adipokines in patients with metabolic syndrome. Kidney Blood Press Res 2012; 35: 226-32.
56. Khan T, Hamilton MP, Mundy DI, Chua SC, Scherer PE. Impact of simvastatin on adipose tissue: pleiotropic effects in vivo. Endocrinology 2009; 150: 5262-72.
57. Mandosi E, Fallarino M, Gatti A, et al. Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes. J Atheroscler Thromb 2010; 17: 539-45.
58. Mallinson JE, Constantin-Teodosiu D, Sidaway J, Westwood FR, Greenhaff PL. Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol 2009; 587: 219-30.
59. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 2012; 172: 144-52.
60. Katsiki N, Banach M. Statin use and risk of diabetes mellitus in postmenopausal women. Clin Lipidol 2012;7: 267-270.
61. Athyros VG, Mikhailidis DP. Pharmacotherapy: statins and newonset diabetes mellitus--a matter for debate. Nat Rev Endocrinol 2012; 8: 133-4.
62. Sattar N, Taskinen MR. Statins are diabetogenic-Myth or reality? Atheroscler Suppl 2012; 13: 1-10.
63. 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.
64. http://www.pharmacytimes.com/publications/issue/2005/2005-03/2005-03-9399
65. Ma T, Tien L, Fang CL, Liou YS, Jong GP. Statins and new-onset diabetes: a retrospective longitudinal cohort study. Clin Ther 2012; 34: 1977-83.
66. Ma T, Chang MH, Tien L, Liou YS, Jong GP. The long-term effect of statins on the risk of new-onset diabetes mellitus in elderly Taiwanese patients with hypertension and dyslipidaemia: a retrospective longitudinal cohort study. Drugs Aging 2012; 29: 45-51.
67. Zaharan NL, Williams D, Bennett K. Statins and Risk of Treated Incident Diabetes in a Primary Care Population. Br J Clin Pharmacol 2012 Jul 30. doi: 10.1111/j.1365-2125.2012.04403.x
68. Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Lipidlowering agents and new onset diabetes mellitus. Expert Opin Pharmacother 2010; 11: 1965-70.
69. Lee CY, Huang KH, Lin CC, Tsai TH, Shih HC. A Neutral Risk on the Development of New-Onset Diabetes Mellitus (NODM) in Taiwanese Patients with Dyslipidaemia Treated with Fibrates. Scientific World Journal 2012; 2012: 392734.
70. Lioudaki E, Ganotakis ES, Mikhailidis DP. Ezetimibe; more than a low density lipoprotein cholesterol lowering drug? An update after 4 years. Curr Vasc Pharmacol 2011; 9: 62-86.
71. Moutzouri E, Liberopoulos E, Mikhailidis DP, et al. Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance. Int J Clin Pract 2011; 65: 1141-8.
72. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet 2010; 375: 735-42.
73. 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.
74. Wright JM. Do statins have a role in primary prevention? An update. Ther Lett 2010; 77: 1-2.
75. Banach M, Mikhailidis DP, Kjeldsen SE, Rysz J. Time for new indications for statins? Med Sci Monit. 2009; 15:MS1-5.
76. Barylski M, Mayszko J, Rysz J, Myβliwiec M, Banach M. Lipids, blood pressure, kidney-what was new in 2011? Arch Med Sci. 2011; 7: 1055-66.
77. 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.
78. Waters DD, JE Ho, A. 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.
79. Newman CB, Szarek M, Colhoun HM, CARDS Investigators et al. The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabet Vasc Dis Res 2008; 5: 177-83.
80. Otocka-Kmiecik A, Rysz J, Banach M. Prodiabetic effect of statins-Do we know the mechanisms of this phenomenon? Post Biochem 2012; 58:195-203.
81. Bielecka-Dabrowa A, Aronow WS, Rysz J, Banach M. Current place of beta-blockers in the treatment of hypertension. Curr Vasc Pharmacol 2010; 8: 733-41.
82. Vulic D, Loncar S, Krneta M, Skrbic R, Lazarevic A, Lee BT, Lopez VA, Wong ND. Risk factor control and adherence to treatment in patients with coronary heart disease in the Republic of Srpska, Bosnia and Herzegovina in 2005-2006. Arch Med Sci 2010; 6, 2: 270-5.
83. Watts GF, Ooi EM. Balancing the cardiometabolic benefits and risks of statins. Lancet 2012; 380: 541-3.
84. Athyros VG, Hatzitolios AI, Karagiannis A, et al. IMproving the imPlemEntation of cuRrent guidelines for the mAnagement of major coronary hearT disease rIsk factors by multifactorial interVEntion. The IMPERATIVE renal analysis. Arch Med Sci 2011; 7:984-92.
85. Mearns BM. Dyslipidemia: Statins and risk of diabetes mellitus. Nat Rev Cardiol 2012; (in press), DOI: 10.1038/nrcardio.2012.126
86. Wang KL, Liu CJ, Chao TF, et al. Statins, Risk of Diabetes, and Implications on Outcomes in the General Population. J Am Coll Cardiol 2012; (in press), DOI:10.1016/j.jacc.2012.05.019.
87. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs (2-28-2012). http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm
88. Athyros VG, Elisaf MS, Alexandrides T, et al; Assessing the Treatment Effect in Metabolic Syndrome Without Perceptible Diabetes (ATTEMPT) Collaborative Group. Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis. Angiology 2012; 63: 358-66.
89. Goldfine AB. Statins: Is It Really Time to Reassess Benefits and Risks? N Engl J Med 2012; 366:1752-5.
90. Katsiki N, Banach M. Statins and the risk of diabetes: the debate. Arch Intern Med. 2012; 172:895-6.
91. Paraskevas KI, Koupidis S, Gentimi F, Tzovaras AA. Statin discontinuation: counterbalancing the benefits with the potential risks. Arch Med Sci 2011; 7:1076-7.