Hidroksi Metil Glutaril Coenzyme-A (HMG CoA) Reduktase Inhibitor and New Onset Diabetes Mellitus: A Review of Correlation and Clinical Implication
DOI:
10.29303/jppipa.v9i9.5274Published:
2023-09-25Issue:
Vol. 9 No. 9 (2023): SeptemberKeywords:
Diabetes mellitus, HMG-CoA reductase inhibitor, Insulin resistance, StatinReview
Downloads
How to Cite
Downloads
Metrics
Abstract
Treatment of lipid abnormalities with HMG CoA reductase inhibitor (statin) has been used for diabetic and non diabetic patients. Various studies have describe increased risk of new onset diabetes associated with statin therapy. This review aims to explain potential mechanism that related to diabetogenic effect of statin. This research was created by collecting literature that relevant to the topic. The types of literature used are clinical trials, meta analyzes and systematic reviews between 2013 until 2021. HMG CoA reductase is the target of statin therapy and the acting of this enzyme is inhibited by statin in competitive way. In vivo and in vitro studies reveal that statin reduce synthesis of mevalonate pathway and increase cholesterol transport that influence B cell function and decrease of insulin sensitivity and insulin secretion by multiple mechanism. Recent genetic study suggest that increased risk of type 2 diabetes mellitus pathway explained by gene variant target for LDL cholesterol lowering drugs. Accumulating evidence from several statin studies suggest that pravastatin is the least diabetogenic statin. Simvastatin, atorvastatin and rosurvastatin are more diabetogenic statin. The used of statin in clinical practice should concerned about benefit on cardiovascular while still considering the possible risk of developing type 2 diabetes mellitus. Regular monitoring of patients glycemic control is mandatory
References
Abbasi F, Lamendola C, Harris CS, Harris V, Tsai M-S, Tripathi P, Abbas F, Reaven GM, Reaven PD, Snyder MP, et al. (2021). Statins are associated with increased insulin resistance and secretion. Arterioscler Thromb Vasc Biol, 41, 2786–2797. https://10.1161/ATVBAHA.121.316159
Angelidi AM, Stambolliu E, Adamopoulou KI, Kousoulis AA. (2018). Is atorvastatin associated with new onset diabetes or deterioration of glycemic control? Systematic review using data from 1.9 Million Patients. Int J Endocrinol, 2018, 8380192. https://doi.org/10.1155/2018/8380192
Azemawah V, Movahed MR, Centuori P, et al. (2019). State of the art comprehensive review of individual statins, their differences, pharmacology, and clinical implications. Cardiovasc Drugs Ther, 33(5),625-39.
Cai R, Yuan Y, Zhou Y, Xia W, Wang P, Sun H, Yang Y, Huang R, Wang S. (2014). Lower intensified target LDL-c level of statin therapy results in a higher risk of incident diabetes: a meta-analysis. PLoS One, 9, e104922. https://doi.org/10.1371/journal.pone.0104922
Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. (2013). Risk of incident diabetes among patients treated with statins: population based study. BMJ, 346, f2610. https://doi.org/10.1136/bmj.f2610
Casula M, Mozzanica F, Scotti L, Tragni E, Pirillo A, Corrao G, Catapano AL. (2017). Statin use and risk of new-onset diabetes: a meta-analysis of observational studies. Nutr Metab Cardiovasc Dis, 27, 396–406. https://doi.org/10.1016/j.numecd.2017.03.001
Ference BA, Robinson JG, Brook RD, Catapano AL, Chapman MJ, Neff DR, Voros S, Giugliano RP, Davey Smith G, Fazio S, et al. (2016). Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med, 375, 2144–2153. https://doi.org/10.1056/NEJMoa1604304
Fong, C.W. (2014). Statins in therapy: Understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3- methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies. Eur. J. Med. Chem, 85, 661–674. https://doi.org/10.1016/j.ejmech.2014.08.037
Galicia-Garcia U, Jebari S, Larrea-Sebal A, et al. (2020). Statin treatment-induced development of type 2 diabetes: From clinical evidence to mechanistic insights. Int J Mol Sci, 21(13), 4725. https://doi.org/10.3390/ijms21134725
Handelsman Y, Jellinger PS, Guerin CK, Bloomgarden ZT, Brinton EA, Budoff MJ, Davidson MH, Einhorn D, Fazio S, Fonseca VA, et al. (2020). Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm - 2020 Executive Summary. Endocr Pract, 26, 1196–1224. https://10.4158/CS-2020-0490
Henriksbo BD, Tamrakar AK, Phulka JS, et al. (2020). Statins activate the NLRP3 inflammasome and impair insulin signaling via p38 and mTOR. Am J Physiol Endocrinol Metab, 319(1), E110-16. https://doi.org/10.1152/ajpendo.00125.2020
Jahanshahi, P.; Wu, R.; Carter, J.D.; Nunemaker, C.S. (2009). Evidence of diminished glucose stimulation and endoplasmic reticulum function in nonoscillatory pancreatic islets. Endocrinology, 150, 607–615. https://doi.org/10.1210/en.2008-0773
Khan SU, Rahman H, Okunrintemi V, Riaz H, Khan MS, Sattur S, Kaluski E, Lincoff AM, Martin SS, Blaha MJ. (2019). Association of lowering low-density lipoprotein cholesterol with contemporary lipid-lowering therapies and risk of diabetes mellitus: a systematic review and meta-analysis. J Am Heart Assoc, 8, e011581. https://doi.org/10.1161/JAHA.118.011581
Ko MJ, Jo AJ, Kim YJ, Kang SH, Cho S, Jo SH, Park CY, Yun SC, Lee WJ, Park DW. (2019). Time- and dose-dependent association of statin use with risk of clinically relevant new-onset diabetes mellitus in primary prevention: a Nationwide Observational Cohort Study. J Am Heart Assoc, 8, e011320. https://doi.org/10.1161/JAHA.118.011320
Navarese EP, Buffon A, Andreotti F, et al. (2013). Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol, 111(8), 1123–30. https://doi.org/10.1016/j.amjcard.2012.12.037
Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, et al; American Heart Association Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint Committee of the Council on Atherosclerosis, Thrombosis and Vascular Biology and Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; and Stroke Council. (2019). Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol, 39, e38–e81. doi: https://doi.org/10.1161/ATV.0000000000000073
Oesterle A, Laufs U, Liao JK. (2017). Pleiotropic effects of statins on the cardiovascular system. Circulation research, 120(1), 229-43. https://doi.org/10.1016/j.amjcard.2012.12.037
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, et al. (2011). Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA, 305, 2556–2564. doi: https://doi.org/10.1001/jama.2011.860
Rocco MB. (2012). Statins and diabetes risk: Fact, fiction, and clinical implications. Clev Clin J Med, 79, 883-93. https://doi.org/10.3949/ccjm.79a.12091
Sampson UK, Linton MF, Fazio S. (2011). Are statins diabetogenic?. Curr Opin Cardiol, 26(4), 342-7. https://doi.org/10.1097/hco.0b013e3283470359
Sattar, N., Preiss, D., Murray, H. M., Welsh, P., Buckley, B. M., de Craen, A. J., Seshasai, S. R., McMurray, J. J., Freeman, D. J., Jukema, J. W., Macfarlane, P. W., Packard, C. J., Stott, D. J., Westendorp, R. G., Shepherd, J., Davis, B. R., Pressel, S. L., Marchioli, R., Marfisi, R. M., Maggioni, A. P., … Ford, I. (2010). Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet (London, England), 375(9716), 735–742. https://doi.org/10.1016/S0140-6736(09)61965-6
Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA, et al; DIAGRAM Consortium; MAGIC Consortium; InterAct Consortium. (2015). HMG-coenzyme a reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet, 385, 351–361. https://doi.org/10.1016/S0140-6736(14)61183-1
Taylor F, Huffman MD, Macedo AF et al. (2013). Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev, CD004816. https://10.1002/14651858.CD004816.pub5
Thakker D, Nair S, Pagada A, Jamdade V, Malik A. (2016). Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf, 25, 1131–1149. https://doi.org/10.1002/pds.4020
Yoon D, Sheen SS, Lee S, Choi YJ, Park RW, Lim HS. (2016). Statins and risk for new-onset diabetes mellitus: a real-world cohort study using a clinical research database. Medicine (Baltimore), 95, e5429. https://doi.org/10.1097/MD. 0000000000005429
Author Biography
Indah Sapta Wardani, Departement of Internal Medicine, Faculty of Medicine, Mataram University
License
Copyright (c) 2023 Indah Sapta Wardani
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with Jurnal Penelitian Pendidikan IPA, agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC-BY License). This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Jurnal Penelitian Pendidikan IPA.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
