Korean Diabetes J.  2009 Dec;33(6):494-502. 10.4093/kdj.2009.33.6.494.

Effects of Adding omega-3 Fatty Acids to Simvastatin on Lipids, Lipoprotein Size and Subspecies in Type 2 Diabetes Mellitus with Hypertriglyceridemia

• Kim WJ
• Lee CB
• Park CY
• Park SE
• Rhee EJ
• Lee WY
• Oh KW
• Park SW
• Kim DJ
• Kim HJ
• Han SJ
• Cho HK

• KMID: 2298055
• DOI: http://doi.org/10.4093/kdj.2009.33.6.494

Abstract

BACKGROUND
omega-3 fatty acids are known to improve lipid profiles, the distribution of lipoprotein subclasses, and secondary prevention against post-myocardial infarction. Rare reports have emerged of synergistic results of omega-3 fatty acids with simvastatin in cases of type 2 diabetes mellitus with hypertriglyceridemia. The purpose of this study was to determine the combined relationship of omega-3 fatty acids plus simvastatin on lipid, lipoprotein size and the types of subspecies. METHODS: This randomized, multi-center, comparison study evaluated eight weeks of combination therapy (omega-3 fatty acids (Omacor) 4 g/day plus simvastatin 20 mg/day) or monotherapy (simvastatin 20 mg/day) for at least six weeks in 62 diabetic patients. Subjects with a triglyceride concentration of more than 200 mg/dL were eligible for inclusion. RESULTS: No significant differences for omega-3 fatty acids + simvastatin versus simvastatin alone were observed for triglycerides (-22.7% vs. -14.3%, P = 0.292), HDL peak particle size (+2.8% vs. -0.4%, P = 0.076), LDL mean particle size (+0.4% vs -0.1%, P = 0.376) or LDL subspecies types, although the combination therapy showed a tendency toward lower triglycerides, larger HDL, and LDL particle sizes than did the monotherapy. There were no significant differences between the two groups in regard to HDL-C, LDL-C, or HbA1c levels. There were no serious adverse events and no abnormalities in the laboratory values associated with this study. CONCLUSION: omega-3 fatty acids were a safeform of treatment in hypertriglyceridemic patients with type 2 diabetes mellitus. But, regarding efficacy, a much larger sample size and longer-term follow-up may be needed to distinguish between the effects of combination therapy and monotherapy.

Keyword

Fatty acids; Hypertriglyceridemia; Omega-3; Simvastatin; Type 2 diabetes mellitus

MeSH Terms

Diabetes Mellitus, Type 2
Fatty Acids
Fatty Acids, Omega-3
Follow-Up Studies
Humans
Hypertriglyceridemia
Infarction
Lipoproteins
Particle Size
Sample Size
Secondary Prevention
Simvastatin
Triglycerides
Fatty Acids
Fatty Acids, Omega-3
Lipoproteins
Simvastatin
Triglycerides

Reference

1. Malmberg K, Yusuf S, Gerstein HC, Brown J, Zhao F, Hunt D, Piegas L, Calvin J, Keltai M, Budaj A. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry. Circulation. 2000. 102:1014–1019.

2. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008. 358:2545–2559.

3. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008. 358:2560–2572.

4. Syvanne M, Taskinen MR. Lipids and lipoproteins as coronary risk factors in non insulin dependent diabetes mellitus. Lancet. 1997. 350:suppl 1. S120–S123.

5. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-years cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993. 16:434–444.

6. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007. 115:450–458.

7. Mueller O, Chang E, Deng D, Franz T, Jing D, Kincaid R, Konigshofer Y, Kratzmeier M, McNulty M, Qian H, Schneider J, Schulte H, Seedorf U, Tian X, Van Cleve M, Yang D, Assmann G. PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol. Clin Chem Lab Med. 2008. 46:490–498.

8. Campos H, Genest JJ Jr, Blijlevens E, McNamara JR, Jenner JL, Ordovas JM, Posner BM, Wilson PW, Schaefer EJ. Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb. 1992. 12:187–195.

9. Koba S, Yokota Y, Hirano T, Ito Y, Ban Y, Tsunoda F, Sato T, Shoji M, Suzuki H, Geshi E, Kobayashi Y, Katagiri T. Small LDL-cholesterol is superior to LDL cholesterol for determining severe coronary atherosclerosis. J Atheroscler Thromb. 2008. 15:250.

10. Barter P, Ginsberg HN. Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia. Am J Cardiol. 2008. 102:1040–1045.

11. Marchioli R, Schweiger C, Tavazzi L, Valagussa F. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lipids. 2001. 36:suppl. S119–S126.

12. Bays H. Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J Cardiol. 2006. 98:71–76.

13. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, Ballantyne CM, Ginsberg HN. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemia patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007. 29:1354–1367.

14. Nordøy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Intern Med. 1998. 243:163–170.

15. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridemia. Heart. 2001. 85:544–548.

16. Dominiczak MH. Hyperlipidaemia and cardiovascular disease: nonfasting triglycerides gain momentum-but nothing changes on the metabolic syndrome front. Curr Opin Lipidol. 2008. 19:326–327.

17. Nordestgaard BG, Been M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007. 298:299–308.

18. Balk E, Lichtenstein AH, Cuhng M, Kupeinick B, Chew P, Lau J. Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease: a systemic review. Atherosclerosis. 2006. 189:19–30.

19. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol. 2008. 102:429–433.

20. Chan DC, Watts GF, Barrett PH, Berlin LJ, Redgrave TG, Mori TA. Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes. 2002. 51:2377–2386.

21. Chan DC, Watts GF, Nguyen MN, Barrett PH. Factorial study of the effect of n-3-fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity. Am J Clin Nutr. 2006. 84:37–43.

22. Valdivielso P, Rioja J, García-Arias C, Sánchez-Chaparro MA, González-Santos P. Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report. Cardiovasc Diabetol. 2009. 8:1–6.

23. Cohen J. Statistical power analysis for the behavioral sciences. 1988. 2nd ed. Hillsdale: Erlbaum.