Diabetology International

, Volume 5, Issue 3, pp 175–180 | Cite as

Effects of non-statin antilipemic drugs on vascular endothelial function in patients with type 2 diabetes with hypercholesterolemia

  • Motoya Koie
  • Yasushi Kondo
  • Tomohiro Santou
  • Yuka Kitamoto
  • Sei Morita
  • Masayuki Yamasaki
  • Mitsuo Fukushima
  • Nobuya Inagaki
  • Koichiro Yasuda
Original Article
  • 138 Downloads

Abstract

Introduction

Type 2 diabetes is a risk factor for atherosclerosis because concomitant hypercholesterolemia further exacerbates hyperglycemia. We compared the efficacy of non-statin and non-fibrate antilipemic drugs in type 2 diabetes patients with hypercholesterolemia, and evaluated the flow-mediated vasodilation (FMD), a marker of early atherosclerotic changes.

Patients and methods

Fifty outpatients (aged 39–79) with type 2 diabetes and low-density lipoprotein cholesterol levels of ≥120 mg/dl were randomly allocated into two groups: 23 patients first received ezetimibe for 4 months followed by eicosapentaenoic acid (EPA) for the next 4 months, and 27 patients first received eicosapentaenoic acid for 4 months followed by ezetimibe for the next 4 months. Glycated hemoglobin and serum lipid levels were measured before and 4 and 8 months after treatment. Ankle brachial pressure index, intimal medial thickness, and FMD were measured in 35 patients. A pretreatment group (group 0) was added. We compared data from groups 0, A (subjects receiving ezetimibe), and B (subjects receiving EPA) during and after treatment.

Results

Non-high-density lipoprotein cholesterol levels decreased significantly in group A compared with groups 0 and B. No significant difference in serum high-density lipoprotein cholesterol levels was observed among the groups, whereas triglyceride levels decreased significantly in group B compared with group 0. FMD increased significantly in groups A and B compared with group 0.

Conclusion

FMD investigation may affect the evaluation of early atherosclerotic changes, and the administration of ezetimibe and EPA may be useful for patients with type 2 diabetes with hypercholesterolemia because it improves vascular endothelial function.

Keywords

Flow-mediated vasodilation Eicosapentaenoic acid Ezetimibe Atherosclerosis Hypercholesterolemia 

References

  1. 1.
    Lerman A, Zeiher AM. Endothelial function—cardiac events. Circulation. 2005;111:363–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–95.PubMedGoogle Scholar
  3. 3.
    Cohn JN, Quyyumi AA, Hollenberg NK et al. Surrogate markers for cardiovascular disease: functional markers. Circulation. 2004; 109(suppl IV):31–46.Google Scholar
  4. 4.
    Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292(21):2585–90.PubMedCrossRefGoogle Scholar
  5. 5.
    Chatzizisis YS, Koskinas KC, Misirli G, et al. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment. Drug Saf. 2010;33(3):171–87.PubMedCrossRefGoogle Scholar
  6. 6.
    Harris WS. N-3 Fatty acids and serum lipoprotein: human studies. Am J Clin Nutr. 1997;65(suppl):1645S–54S.PubMedGoogle Scholar
  7. 7.
    Tagawa H, Shimokawa H, Tagawa T, et al. Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease. J Cardiovasc Pharmacol. 1999;33:633–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Yano T, Kawano H, Yamashita M, et al. Effects of ethyl-all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), pravastatin and their combination serum lipids and intimal thickening of cuff-sheathed carotid artery in rabbits. Life Sci. 1997;61:2007–15.Google Scholar
  9. 9.
    Sato M, Katsuki Y, Kanehiro H, et al. Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on the physical properties of arterial walls in high cholesterol diet-fed rabbits. J Cardiovasc Pharmacol. 1993;22:1–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Calder PC. Polyunsaturated fatty acids, inflammation, and immunity. Lipids. 2001;35:1007–24.CrossRefGoogle Scholar
  11. 11.
    Knapp HR. Dietary fatty acids in human thrombosis and hemostasis. Am J Clin Nutr. 1997;65(suppl):1687S–98S.PubMedGoogle Scholar
  12. 12.
    West SG, Hecker KD, Mustad VA, et al. Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes. Diabetologia. 2005;48(1):113–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Goodfellow J, Bellamy MF, Ramsey MW, et al. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol. 2000;35(2):265–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Kastelein JJP, Akdim F, Stroes ESG, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima–media thickness. N Engl J Med. 2009;361(22):2113–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Meaney A, Ceballos G, Asbun J, et al. The VYtorin on Carotid intima–media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009;49(7):838–47.Google Scholar
  17. 17.
    Miyashita Y, Endo K, Saiki A, et al. Effect of ezetimibe monotherapy on lipid metabolism and arterial stiffness assessed by cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb. 2010;17(10):1070–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Maki-Petaja KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll. 2007;50(9):852–8.CrossRefGoogle Scholar
  19. 19.
    Yunoki K, Nakamura K, Miyoshi T, et al. Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. Atherosclerosis. 2011;217(2):486–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Nakamura T, Hirano M, Kitta Y, et al. A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. J Cardiol. 2012;60(1):12–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Yunoki K, Nakamura K, Miyoshi T, et al. Impact of hypertriglyceridemia on endothelial dysfunction during statin ± ezetimibe therapy in patients with coronary heart disease. Am J Cardiol. 2011;108(3):333–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Ishiguro J, Tada T, Ogihara T, et al. Studies on the metabolic disposition of ethyl eicosapentaenoate (EPA-E) in rats and dogs. Drug Metab Pharmacokinet. 1987;2(6):683–702.Google Scholar
  23. 23.
    Patrick JE, Kosoglou T, Stauber KL, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos. 2002;30(4):430–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Sever PS, Poulter NR, Dahlof B, et al. The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure. Eur Heart J. 2008;29(4):499–508.Google Scholar
  25. 25.
    Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Diabetes Society 2013

Authors and Affiliations

  • Motoya Koie
    • 1
  • Yasushi Kondo
    • 1
    • 2
  • Tomohiro Santou
    • 1
  • Yuka Kitamoto
    • 1
  • Sei Morita
    • 1
  • Masayuki Yamasaki
    • 3
  • Mitsuo Fukushima
    • 4
  • Nobuya Inagaki
    • 2
  • Koichiro Yasuda
    • 1
  1. 1.Department of Diabetology and EndocrinologyOsaka Saiseikai Noe HospitalOsakaJapan
  2. 2.Department of Diabetes, Endocrinology and Nutrition, Graduate School of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of Clinical ExaminationOsaka Saiseikai Noe HospitalOsakaJapan
  4. 4.Department of Nutrition Science, Faculty of Health and Welfare ScienceOkayama Prefectural UniversityOkayamaJapan

Personalised recommendations