Low concentration of plasma cholesterol and type 2. diabetes mellitus

Czech version

Authors: Jaroslav A. Hubáček ^1,2
Authors‘ workplace: Centrum experimentální medicíny, IKEM, Praha ¹; III. interní klinika – klinika endokrinologie a metabolismu 1. LF UK a VFN v Praze ²
Published in: AtheroRev 2021; 6(1): 40-43
Category:

Overview

Statins are the most commonly prescribed drugs, effective and with a low incidence of undesirable side effects. Among the undesirable side effects of statin therapy, the increased risk of type 2 diabetes (T2DM) is discussed. A quarter of century ago, a lower incidence of diabetes was observed in patients with familial hypercholesterolemia. Increased risk of T2DM in statin users has also been observed in some clinical trials. A Mendelian randomization study showed that the increased risk of developing T2DM has causality in the inhibition of HMGCoA reductase activity – activity, whose is blocked by statins. Other genes whose variants have been used as “proxies” to analyze the causality between lowering cholesterol and increasing the risk of T2DM are NPC1L1 (an inhibitor of intestinal cholesterol absorption) and PCSK9 (a protein that controls LDL-receptor degradation). Also here has been confirmed, that genetic variants associated with lower cholesterol levels are also associated with increased risk of T2DM. The risk assessment of the development of complex “civilization” noncommunicable diseases should be strictly individualized and comprehensive, with careful consideration of all potential undesirable side effects of (not only) dyslipidemic treatment for each individual.

Keywords:

diabetes – ezetimibe – familial hypercholesterolemia – Genetics – mendelian randomisation – PCSK9 inhibitor – statin

Sources

Guirgis FW, Donnelly JP, Dodani S et al. Cholesterol levels and long-term rates of community-acquired sepsis. Crit Care 2016; 20(1): 408. Dostupné z DOI: <http://10.1186/s13054–016–1579–8>.
Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol 2020; 21(4): 225–245. Dostupné z DOI: <http://10.1038/s41580–019–0190–7>.
Soška V, Kyselák O. Co je nového v léčbě hypercholesterolémie? Interni Med 2016; 18(1): 6–8. Dostupné z WWW: <https://www.internimedicina.cz/pdfs/int/2016/01/02.pdf>.
Goláň L. Chyby a úskalí terapie statiny. Interni Med 2003; 5(11): 552–553. Dostupné z WWW: <http://www.internimedicina.cz/pdfs/int/2003/11/06.pdf>.
Vrablík M. Inhibitory PCSK9 ve světle posledních údajů. Interv Akut Kardiol 2016; 15(1): 54–57. Dostupné z WWW: <https://www.iakardiologie.cz/pdfs/kar/2016/01/10.pdf>.
Karásek D. Ezetimib v léčbě hypercholesterolemie. Interni Med 2019; 21(2): 112–116. Dostupné z WWW: <https://www.internimedicina.cz/pdfs/int/2019/02/10.pdf>.
Haluzík M. Metformin a jeho postavení v léčbě diabetes mellitus 2. typu. Interni Med 2014; 16(2): 67–69. Dostupné z WWW: <https://www.internimedicina.cz/pdfs/int/2014/02/05.pdf>.
Krejčí H. Diabetes mellitus 2. typu – od porozumění patogeneze k možnostem jeho remise. DMEV 2020; 23(2): 53–65. Dostupné z WWW: <http://www.tigis.cz/images/stories/DMEV/2020/DMEV_2_2020/DMEV_2_2020_krejcil.pdf>.
Vrablík M. Co se děje v současnosti kolem statinů? Remedia 2013; 23: 151–154. Dostupné z WWW: <http://www.remedia.cz/Okruhy-temat/Endokrinologie-a-metabolismus/Co-se-deje-v-soucasnosti-kolem-statinu/8-W-1tf.magarticle.aspx>.
Piťha J. Aktuální klinická data o vybraných nežádoucích účincích statinů: diabetes mellitus, kognitivní, renální a hepatální funkce, krvácivé mozkové příhody a katarakta. Konsensus odborníků Evropské společnosti pro aterosklerózu. Hyper Kardiovask Prevence 2020; 1: 6–12. Dostupné z WWW: http://hypertension.cz/sqlcache/hypertenze-cislo-1–2020.pdf
Katsiki N, Athyros VG, Karagiannis A et al. Statins and type 2 diabetes mellitus: an update after 1 year. Curr Pharm Des 2016; 22(18): 2723–2735. Dostupné z DOI: <http://dx.doi.org/10.2174/1381612822666160125114626>.
Vaclová M, Vrablík M. Novinky o familiární hypercholesterolémii pro kardiology. Kardiol Rev 2019; 2: 60–67. Dostupné z WWW: https://www.kardiologickarevue.cz/casopisy/kardiologicka-revue/2019–2-18/novinky-o-familiarni-hypercholesterolemii-pro-kardiology-113073/download?hl=cs
Vrablik M, Tichy L, Freiberger T et al. Genetics of familial hypercholesterolemia: New insights. Front Genet 2020; 11: 574474. Dostupné z WWW: <https://www.frontiersin.org/articles/10.3389/fgene.2020.574474/full>.
Vohl MC, Gaudet D, Moorjani S et al. Comparison of the effect of two low-density lipoprotein receptor class mutations on coronary heart disease among French-Canadian patients heterozygous for familial hypercholesterolaemia. Eur J Clin Invest 1997; 27(5): 366–373. Dostupné z DOI: <http://dx.doi.org/10.1046/j.1365–2362.1997.1250669.x>.
Climent E, Pérez-Calahorra S, Marco-Benedí V et al. Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia. Sci Rep 2017; 7: 5596. Dostupné z DOI: <http://dx.doi.org/10.1038/s41598–017–06101–6>.
Besseling J, Kastelein JJ, Defesche JC et al. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 2015; 313(10): 1029–1036. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2015.120>.
Fuentes F, Alcala-Diaz JF, Watts GF et al. Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study. Int J Cardiol 2015; 201: 79–84. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ijcard.2015.07.107>.
Ridker PM, Pradhan A, MacFadyen JG et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012; 380(9841): 565–571. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(12)61190–8>.
Hubáček J.A. Mendelovské randomizační studie: princip a příklady využití v oblasti kardiovaskulární medicíny. AtheroRev 2020; 5(3): 176–180. Dostupné z WWW: <https://www.atheroreview.eu/casopisy/athero-review/2020–3-23/mendelovske-randomizacni-studie-princip-a-priklady-vyuziti-v-oblasti-kardiovaskularni-mediciny-124884/download?hl=cs>.
Sekula P, Del Greco M F, Pattaro C et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016; 27(11): 3253–3265. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2016010098>.
Swerdlow DI, Preiss D, Kuchenbaecker KB et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 2015; 385(9965): 351–361. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)61183–1>.
Lotta LA, Sharp SJ, Burgess S et al. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: A Meta-analysis. JAMA 2016; 316(13): 1383–1391. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2016.14568>.
White J, Swerdlow DI, Preiss D et al. Association of lipid fractions with risks for coronary artery disease and diabetes. JAMA Cardiol. 2016; 1(6): 692–699. Dostupné z DOI: <http://dx.doi.org/10.1001/jamacardio.2016.1884>.
Besseling J, Hutten BA. Is there a link between diabetes and cholesterol metabolism? Expert Rev Cardiovasc Ther 2016; 14(3): 259–261. Dostupné z DOI: <http://dx.doi.org/10.1586/14779072.2016.1133292>.
Muscogiuri G, Sarno G, Gastaldelli A et al. The good and bad effects of statins on insulin sensitivity and secretion. Endocr Res 2014; 39(4): 137–143. Dostupné z DOI: <http://dx.doi.org/10.3109/07435800.2014.952018>.
Sampson UK, Linton MF, Fazio S. Are statins diabetogenic? Curr Opin Cardiol 2011; 26(4): 342–347. Dostupné z DOI: <http://dx.doi.org/10.1097/HCO.0b013e3283470359>.
Carmena R, Betteridge DJ. Diabetogenic action of statins: Mechanisms. Curr Atheroscler Rep 2019; 21(6): 23. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–019–0780-z>.
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(9716): 735–742. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(09)61965–6>.