A retrospective study on the impact of statins on blood glucose levels in Lebanese controlled type two diabetic patients
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Abstract
Objective: The American Food and Drug Administration have warned about a possible association between statins and the development of new-onset diabetes. Lebanese studies lack sufficient data about this correlation. This study was conducted to evaluate the clinical implication of statins on blood glucose levels among diabetic Lebanese hospitalized patients.
Methods: A four-month retrospective observational study was conducted from February till May 2017. It included 131 type II diabetic patients stabilized on statins for a minimum of one year. In addition to statin type, strength, and duration, fasting blood glucose (FBG), glycosylated hemoglobin (Hba1c), body mass index (BMI), and lipid profiles were recorded.
Results: The mean baseline FBG levels before the initiation of statins and post-statin intake were 115.25 mg/dL and 175.81 mg/dL for atorvastatin 10mg, 110.63 mg/dL and 183.16 mg/dL for atorvastatin 20mg, 119.25 mg/dL and 189.11mg/dl for atorvastatin 40mg, 123.21mg/dL and 202.05mg/dL for rosuvastatin 10mg, 114.53 mg/dL and 169.50 mg/dL for rosuvastatin 20mg, and 118.56 mg/dL and 174.64mg/dL for simvastatin 20mg. The association between statins at different doses and mean FBG levels was statistically significant (p<0.05). The mean baseline glycosylated hemoglobin before statin prescription was 5.63% and significantly increased to 7.5% three months after statin intake (p-value of 0.03).
Conclusion: In view of the evidence, it is difficult to refute that an association exists between statin use and elevated blood glucose levels. Patients on statins should carefully monitor their glucose levels to assess the risk and benefit of statin use.
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References
[2]. Bellosta S, Paoletti R, and Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109, 23 Suppl 1: III-50.
[3]. US Food and Drug Administration. Statin drugs—drug safety communication: class labelling change. 2012. https://www.fda.gov. Accessed 13 Jul 2016
[4]. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C- reactive protein. N Engl J Med. 2008; DOI: 10.1056/NEJMoa0807646
[5]. 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(3):357–62.
[6]. 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.
[7]. Sever PS, Dahlof B, Poulter NR, et al. ASCOT investigators Prevention of coronary and stroke events with atorvastatin in hyper-tensive 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. Lancet.2003;361:1149–58.
[8]. Henriksbo BD, Lau TC, Cavallari JF, et al. Fluvastatin causes NLRP3 inflammasome-mediated adipose insulin resistance. Diabetes. 2014; Doi:10.2337/db13-1398.
[9]. Wen H, Gris D, Lei Y, et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011; 12:408–415pmid:21478880.
[10]. Mitchell P, Marette A: Statin-induced insulin resistance through inflammasome activation: sailing between Scylla and Charybdis. Diabetes.2014; Doi: 10.2337/db14-1059.
[11]. 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(10):5136–45.
[12]. Nakata M, Nagasaka S, Kusaka I, et al. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49(8):1881–92.
[13]. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A. 1990;87(22):8931–4.
[14]. Goto T, Nagai H, Egawa K, et al. Farnesyl pyrophosphate regulates adipocyte functions as an endogenous PPARgamma agonist. Biochem J. 2011;438(1):111–9.
[15]. Carlberg M, Dricu A, Blegen H, et al. Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin- like growth factor-1 receptor to the cell surface: evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth. J Biol Chem. 1996;271(29):17453–62.
[16]. Chetboun M, Abitbol G, Rozenberg K, et al. Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin. J Cell Biochem. 2012;113(6):1966–76.
[17]. Maeda T, Horiuchi N. Simvastatin suppresses leptin expression in 3 T3-L1 adipocytes via activation of the cyclic AMP-PKA pathway induced by inhibition of protein prenylation. J Biochem. 2009;145(6):771–81.
[18]. Azar ST, Hantash HA, Jambart S, et al. Factors influencing dyslipidemia in statin-treated patients in Lebanon and Jordan: results of the Dyslipidemia International Study. Vasc Health Risk Manag. 2014; 10:225-35.
[19]. El Masr FA, Soubra L, Kabbani S, et al. Patterns of statins prescription, and goals attainments in a sample of Lebanese patients: a retrospective study (abstract) retrieved from https://www.bau.edu.lb/Pharmacy/Thesis/2010-2011
[20]. Yamakawa T, Takano T, Tanaka S, Kadonosono K, Terauchi Y. Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus. J Atheroscler Thromb. 2008; 15:269–275.
[21]. Kryzhanovski V, Gumprecht J, Zhu B, Yu CY, Hounslow N, Sponseller CA. Atorvastatin but not pitavastatin significantly increases fasting plasma glucose in patients with type 2 diabetes and combined dyslipidemia (abstract). J Am Coll Cardiol. 2011; 57: E575.
[22]. Simsek S, Schalkwijk CG, Wolffenbuttel BH. Effects of rosuvastatin and atorvastatin on glycaemic control in type 2 diabetes—the CORALL study. Diabet Med. 2012; 29:628–631.
[23].Angelidi A, Stambolliu E, Adamopoulou K, et al.Is atorvastatin associated with new onset diabetes or deterioration of glycemic control? Systemic review using data from 1.9 million patients. Int J Endocrinol 2018: 17, ID 8380192.
[24]. Cederberg H, Stančáková A, Yaluri N, et al.: 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. 2015;58(5):1109–17.
[25]. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a metaanalysis. JAMA. 2011; 305; Doi: 10.1001/jama.2011.860.
[26]. Yousef A, Tu JV, Wang J, Donovan L, Ko DT. The association of intensive statin therapy on long-term risks of cardiovascular events and diabetes following acute myocardial infarction (abstract). Circulation. 2012; 125: e859.
[27]. Hashiguchi M, Maruyama J, Shimizu M, et al. Risk factor for diabetes mellitus and high blood glucose with HMG-CoA reductase inhibitors using a postmarketing surveillance database in Japan. Clin Pharmacol Drug Dev 2018; 7(8): 800-810.