#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A near future of treatment of dyslipidemia in type 2 diabetics


Authors: Michal Vrablík
Authors‘ workplace: Centrum preventivní kardiologie III. interní kliniky – kliniky endokrinologie a metabolizmu 1. LF UK a VFN v Praze
Published in: Vnitř Lék 2016; 62(7-8): 652-660
Category: Reviews

Overview

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).

Key words:
anti-sense therapy – diabetic dyslipidemia – ezetimibe – fibrates – PCSK9 inhibitors – resins – statins


Sources

1. Češka R. Cholesterol a ateroskleróza, léčba dyslipidémií. Triton: Praha 2005. ISBN 80–7254–738–0.

2. Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome – new worldwide definition. Lancet 2005; 366(9491): 1059–1062.

3. 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.

4. Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet 2004; 5: 189–218.

5. 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.

6. 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>.

7. 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.

8. 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.

9. 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.

10. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014; 384(9943): 626–635.

11. 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.

12. 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.

13. Soška V. Léčba dyslipidemie u diabetiků. Interní Med 2007; 9(4): 163–166.

14. 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.

15. 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>.

16. 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>.

17. 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.

18. 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.

19. Špinar J, Špinarová L, Vítovec J. Studie IMPROVE-IT u pacientů s diabetes mellitus. Kardiol Rev Int Med 2015; 17(3): 253–256.

20. Handelsman Y. Role of bile acid sequestrants in the treatment of type 2 diabetes. Diabetes Care 2011; 34(Suppl 2): S244-S250.

21. 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.

22. Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond) 2011; 25(7): 843–849.

23. 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>.

24. Fruchart JC. Selective peroxisome proliferator-activated receptorα modulators (SPPARMα): 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>.

25. 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.

26. 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.

27. 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.

28. Vrablík M. Biologická léčba v kardiologii: nové studie s protilátkami proti PCSK9. Acta Medicinae 2015; 4(1): 15–18.

29. 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.

30. 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.

31. 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.

32. 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.

33. Češka R, Táborský M, Vrablík M. Stanovisko k nové moderní hypolipidemické léčbě. Vnitř Lék 2015; 61(11): 933–935.

34. 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>.

35. 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.

36. 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>.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 7-8

2016 Issue 7-8

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#