Vnitr Lek 2016, 62(7-8):652-660
A near future of treatment of dyslipidemia in type 2 diabetics
- Centrum preventivní kardiologie III. interní kliniky - kliniky endokrinologie a metabolizmu 1. LF UK a VFN v Praze
Dyslipidemia in type 2 diabetics represents a complex change of lipoprotein metabolism that is highly proatherogenic. It originates on a genetic background in the context of insulin resistance and affects lipoprotein metabolism at multiple levels (e.g. hepatocyte, enterocyte, intravascular processing) mainly in the postprandial phase. The treatment of diabetic (atherogenic) dyslipidemia is an effective option to lower the risk of both macro- and microvascular complications of diabetes. Lifestyle changes effectively impact on dyslipidemia in diabetics, however, it is impossible to reach treatment goals and achieve necessary risk reduction without lipid lowering medications. Statins remain the corner stone of pharmacological therapy and they should be combined with ezetimibe (or a resin) in case of insufficient LDL-cholesterol lowering or with fenofibrate when triglyceride levels remain elevated. In near future these drugs will be available in new fixed-dose combination formulas. Moreover, very soon PCSK9 inhibitors will get to clinical practice offering patients with diabetes additional LDL-cholesterol lowering by more than 50 %. Selective modulators of PPARα receptors are under development and these shall offer better efficacy and tolerability compared with fibrates. Other future options for the management of diabetic dyslipidemia will be drugs utilizing the anti-sense technology interfering with translation of genes coding for metabolic pathways of lipoprotein species typically perturbed in type 2 diabetes (e.g. anti-sense oligonucleotides against mRNA of apolipoprotein CIII).
Keywords: anti-sense therapy; diabetic dyslipidemia; ezetimibe; fibrates; PCSK9 inhibitors; resins; statins
Received: August 11, 2016; Accepted: August 15, 2016; Published: July 1, 2016 Show citation
References
- Češka R. Cholesterol a ateroskleróza, léčba dyslipidémií. Triton: Praha 2005. ISBN 80-7254-738-0.
- Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome - new worldwide definition. Lancet 2005; 366(9491): 1059-1062.
Go to original source...
Go to PubMed...
- Grundy SM, Cleeman JI, Merz CN et al. [Coordinating Committee of the National Cholesterol Education Program]. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Arterioscler Thromb Vasc Biol 2004; 24(8): e149-e161.
Go to original source...
Go to PubMed...
- Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet 2004; 5: 189-218.
Go to original source...
Go to PubMed...
- Adiels M, Olofsson SO, Taskinen MR et al. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Atheroscler Thromb Vasc Biol 2008; 28(7): 1225-1236.
Go to original source...
Go to PubMed...
- Hsieh J, Hayashi AA, Webb J et al. Postprandial dyslipidemia in insulin resistence: Mechanisms and role of intestinal insulin sensitivity. Atheroscler Suppl 2008; 9(2): 7-13. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosissup.2008.05.011>.
Go to original source...
Go to PubMed...
- Rivellese AA, De Natale C, Di Marino L et al. Exogenous and endogenous postprandial lipid abnormalities in type 2 diabetic patients with optimal blood glucose control and optimal fasting triglyceride levels. J Clin Endocrinol Metab 2004; 89(5): 2153-2159.
Go to original source...
Go to PubMed...
- Varbo A, Benn M, Nordestgaard BG. Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment. Pharmacol Ther 2014; 141(3): 358-367.
Go to original source...
Go to PubMed...
- Jorgensen AB, Frikke-Schmidt R, West AS et al. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013; 34(24): 1826-1833.
Go to original source...
Go to PubMed...
- Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014; 384(9943): 626-635.
Go to original source...
Go to PubMed...
- Nordestgaard BG, Langsted A, Mora S et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016; 37(35): 1944-1958.
Go to original source...
Go to PubMed...
- Catapano AL, Reiner Z, 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). Atherosclerosis 2011; 217(1): 3-46.
Go to original source...
Go to PubMed...
- Soška V. Léčba dyslipidemie u diabetiků. Interní Med 2007; 9(4): 163-166.
- Kearney PM, Blackwell L, Collins R et al. [Cholesterol Treatment Trialists' (CTT) Collaborators]. Efficacy of cholesterol-lowering therapy in 18686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371(9607): 117-125.
Go to original source...
Go to PubMed...
- de Vries FM, Kolthof J, Postma MJ et al. Efficacy of Standard and Intensive Statin Treatment for the Secondary Prevention of Cardiovascular and Cerebrovascular Events in Diabetes Patients: A Meta-Analysis. PLoS ONE 2014; 9(11): e111247. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0111247>.
Go to original source...
Go to PubMed...
- Huang CH, Huang YY, Hsu BR. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. J Diabet Invest 2016; Jan 18. Dostupné z DOI: <http://dx.doi.org/10.1111/jdi.12483>.
Go to original source...
Go to PubMed...
- Baigent C, Landray MJ, Reith C et al. [SHARP Investigators]. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377 (9784): 2181-2192.
Go to original source...
Go to PubMed...
- Cannon CP, Blazing MA, Giugliano RP et al. [IMPROVE-IT Investigators]. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372(25): 2387-2397.
Go to original source...
Go to PubMed...
- Špinar J, Špinarová L, Vítovec J. Studie IMPROVE-IT u pacientů s diabetes mellitus. Kardiol Rev Int Med 2015; 17(3): 253-256.
- Handelsman Y. Role of bile acid sequestrants in the treatment of type 2 diabetes. Diabetes Care 2011; 34(Suppl 2): S244-S250.
Go to original source...
Go to PubMed...
- Ginsberg HN, Elam MB, Lovato LC et al. [ACCORD Study Group]. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362(17): 1563-1574.
Go to original source...
Go to PubMed...
- Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond) 2011; 25(7): 843-849.
Go to original source...
Go to PubMed...
- Cha KH, Cho KJ, Kim MS et al. Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide. Int J Nanomedicine 2012; 7: 5565-5575. Dostupné z DOI: <http://dx.doi.org/10.2147/IJN.S36939>.
Go to original source...
Go to PubMed...
- Fruchart JC. Selective peroxisome proliferator-activated receptorα modulators (SPPARM&alpha): The next generation of peroxisome proliferator-activated receptor α-agonists. Cardiovasc Diabetol 2013; 12: 82. Dostupné z DOI: <http://dx.doi.org/10.1186/1475-2840-12-82>.
Go to original source...
Go to PubMed...
- Foucher C, Aubonnet P, Reichert P et al. [Cholib study Investigators]. New Fixed-Dose Combinations of Fenofibrate/Simvastatin Therapy Significantly Improve the Lipid Profile of High-Risk Patients with Mixed Dyslipidemia Versus Monotherapies. Cardiovasc Ther 2015; 33(6): 329-337.
Go to original source...
Go to PubMed...
- Hatala R, Pella D, Hatalová K et al. Optimization of blood pressure treatment with fixed-combination perindopril/amlodipine in patients with arterial hypertension. Clin Drug Investig 2012; 32(9): 603-612.
Go to original source...
- Sever P, Dahlof B, Poulter N et al. [ASCOT Steering Committee Members]. Potential synergy between lipid-lowering and blood-pressure lowering in the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J 2006; 27(24): 2982-2988. Erratum in Eur Heart J 2007; 28(1): 142.
Go to original source...
Go to PubMed...
- Vrablík M. Biologická léčba v kardiologii: nové studie s protilátkami proti PCSK9. Acta Medicinae 2015; 4(1): 15-18.
- Češka R. Inhibice PCKS9 jako nová naděje pro nemocné s familiární hypercholesterolemií, statinovou intolerancí a posléze pro všechny pacienty v nejvyšším kardiovaskulárním riziku? Zaměřeno na alirocumab - Praluent. Vnitř Lék 2015; 61(11): 946-951.
Go to PubMed...
- Lipinski MJ, Escarcega RO, Lhermusier T et al. The impact of PCSK9 Inhibitors on lipid levels and outcomes in patients with primary hypercholesterolemia: a network meta-analysis. Eur Heart J 2016; 37(6): 536-545.
Go to original source...
Go to PubMed...
- Blom DJ, Hala T, Bolognese M et al. [DESCARTES Investigators]. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014; 370(19): 1809-1819.
Go to original source...
Go to PubMed...
- Robinson JG, Farnier M, Krempf M et al. [ODYSSEY LONG TERM Investigators]. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372(16): 1489-1499.
Go to original source...
Go to PubMed...
- Češka R, Táborský M, Vrablík M. Stanovisko k nové moderní hypolipidemické léčbě. Vnitř Lék 2015; 61(11): 933-935.
Go to PubMed...
- Sattar N, Preiss D, Robinson JG et al. Lipid-Lowering Efficacy of the PCSK9 Inhibitor Evolocumab (AMG 145) in Patients with Type 2 Diabetes: a Meta-analysis of Individual Patient Data. Lancet Diabetes Endocrinol 2016; 4(5): 403-410. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213-8587(16)00003-6>.
Go to original source...
Go to PubMed...
- Kastelein JJ, Wedel MK, Baker BF et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 2006; 114(16): 1729-1735.
Go to original source...
Go to PubMed...
- Kramer W. Antilipidemic drug therapy of today and in the future. Handb Exp Pharmacol 2016; 233: 373-435. Dostupné z DOI: <http://dx.doi.org/10.1007/164_2015_15>.
Go to original source...
Go to PubMed...