Skip to main content
SpringerLink
Log in

Impact of eicosapentaenoic acid/arachidonic acid ratio on left ventricular structure in patients with diabetes

  • Original Article
  • Published:
Diabetology International Aims and scope Submit manuscript

Abstract

Objective

This study aimed at investigating the relationship among the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio, the left ventricular (LV) structure and function in patients with diabetes.

Research design and methods

Inpatients with diabetes (n = 91) were included in the study. Serum fatty acid levels (EPA, AA, and docosahexaenoic acid) and lipid profiles were measured. The LV dimension and wall thickness were measured using echocardiography.

Results

The mean age was 56 ± 17 years, and 49 % were men. The average number of days per week with a fish-based diet was 4 ± 2. The mean EPA/AA ratio was 0.34 ± 0.18. Linear regression analysis identified no significant relationships between EPA/AA ratio and LV parameters. Setting the study-specific threshold value of the EPA/AA ratio group at 0.43, which indicates the highest value of EPA/AA ratio group calculated by quartiles, the higher group (EPA/AA ≥0.43) and the lower group (EPA/AA <0.43) were compared for LV parameters. Interventricular septal thickness and posterior wall thickness were significantly thinner in the higher EPA/AA ratio group than the lower group (p < 0.05, respectively). Left ventricular mass index was not significantly different between the groups. In multiple regression analysis, the association between the higher EPA/AA ratio group and LV wall thickness remained significant after adjustments for confounding variables (p = 0.01, p < 0.05, respectively).

Conclusions

A higher EPA/AA ratio was associated with reduced LV wall thickness. The EPA/AA ratio may play an important role in preventing LV wall thickness in patients with diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Caterina RD. n-3 fatty acids in cardiovascular disease. N Engl J Med. 2011;364:2439–50.

    Article  PubMed  Google Scholar 

  2. Din JN, Newby DE, Flapan AD. Omega 3 fatty acids and cardiovascular disease-fishing for a natural treatment. BMJ. 2004;328:30–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Thie F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, Grimble RF. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomized controlled trial. Lancet. 2003;361:477–85.

    Article  Google Scholar 

  4. Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oil. Circulation. 2003;107:2646–52.

    Article  PubMed  Google Scholar 

  5. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: meta regression analysis of randomized trials. J Hypertens. 2002;20:1493–9.

    Article  CAS  PubMed  Google Scholar 

  6. Lee TH, Hoover RL, Williams JD, Sperling RI, Ravalese J 3rd, Spur BW, Robinson DR, Corey EJ, Lewis RA, Austen KF. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotorien generation and neutrophil function. N Eng J Med. 1985;312:1217–24.

    Article  CAS  Google Scholar 

  7. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Eng J Med. 1989;320:265–71.

    Article  CAS  Google Scholar 

  8. Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol. 2009;32:365–72.

    Article  PubMed  Google Scholar 

  9. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ichikawa Y, Oikawa S, Sakai J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzaka Y. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease -secondary prevention analysis from JELIS. Circ J. 2009;73:1283–90.

    Article  CAS  PubMed  Google Scholar 

  10. Oikawa S, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ichikawa Y, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K. Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: sub-analysis of the Japan EPA lipid intervention study (JELIS). Atherosclerosis. 2009;206:535–9.

    Article  CAS  PubMed  Google Scholar 

  11. Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, Hanafusa T, Haneda M, Ueki K. Report of the Committee of the diagnostic criteria of diabetes mellitus: the Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus. Diabetol Int. 2010;1:2–20.

    Article  Google Scholar 

  12. Kashiwagi A, Kasuga M, Araki E, Oka Y, Hnafusa T, Ito H, Tominaga M, Oikawa S, Noda M, Kawamura T, Sanke T, Namba M, Hashiramoto M, Sasahara T, Nishio Y, Kuwa K, Ueki K, Takei I, Umemoto M, Murkami M, Yamakado M, Yatomi Y, Ohashi H, Committee on the Standardization of Diabetes Mellitus-Related Laboratory Testing of Japan Diabetes Society. International clinical harmonization of glycated hemoglobin in Japan: from Japan diabetes society to National Glycohemoglobin Standardization Program values. Diabetol Int. 2012;3:8–10.

    Article  Google Scholar 

  13. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A. Collaborators developing the Japanese equation for GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  PubMed  Google Scholar 

  14. Devereux RB, Reicheck N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation. 1977;55:613–8.

    Article  CAS  PubMed  Google Scholar 

  15. Yano Y, Hoshide S, Tamaki N, Inokuchi T, Nagata M, Yokota N, Hidaka T, Kanemaru Y, Matsuda S, Kuwabara M, Shimada K, Kario K. Regional differences in hypertensive cardiovascular remodeling between fishing and farming communities in Japan. Am J Hypertens. 2011;24:437–43.

    Article  CAS  PubMed  Google Scholar 

  16. Duda MK, O’Shea KM, Tintinu A, Xu W, Khairallah RJ, Barrows BR, Chess DJ, Azimzadeh AM, Harris WS, Sharov VG, Sabbah HN, Stanley WC. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovasc Res. 2009;81:319–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, American College of Cardiology Foundation, American Heart Association. 2009 focused update incorporated into the ACC/AHA, 2005 guidelines for the diagnosis and management of heart failure in adults, a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines developed in collaboration with the international society for heart and lung transplantation. J Am Coll Cardiol. 2009;53:1–90.

    Article  Google Scholar 

  18. Palmieri V, Tracy RP, Roman MJ, Liu JE, Best LG, Bella JN, Robbins DC, Howard BV, Devereux RB, Strong Heart Study. Relation of left ventricular hypertrophy to inflammation and albuminuria in adults with type 2 diabetes: the strong heart study. Diabetes Care. 2003;26:2764–969.

    Article  PubMed  Google Scholar 

  19. Romen MJ, Pickering TG, Schwartz JE, Pini R, Devereux RB. Association of carotid atherosclerosis and left ventricular hypertrophy. J Am Coll Cardiol. 1995;25:83–90.

    Article  Google Scholar 

  20. Lindholm LH, Ibsen H, Dahlöf B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S, LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:1004–10.

    Article  CAS  PubMed  Google Scholar 

  21. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793–801.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kuwahara F, Kai H, Tokuda K, Niiyama H, Tahara N, Kusaba K, Takemiya K, Jalalidin A, Koga M, Nagata T, Shibata R, Imaizumi T. Roles of intercellular adhesion molecule-1 in hypertensive cardiac remodeling. Hypertension. 2003;41:819–23.

    Article  CAS  PubMed  Google Scholar 

  23. Bozkurt B, Kribbs SB, Clubb FJ Jr, Michael LH, Didenko VV, Hornsby PJ, Seta Y, Oral H, Spinale FG, Mann DL. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998;97:1382–91.

    Article  CAS  PubMed  Google Scholar 

  24. Masiha S, Sundström J, Lind L. Inflammatory markers are associated with left ventricular hypertrophy and diastolic dysfunction in a population-based sample of elderly men and women. J Hum Hypertens. 2013;27:13–7.

    Article  CAS  PubMed  Google Scholar 

  25. Bo S, Mandrile C, Milanesio N, Pagani A, Gentile L, Gambino R, Villois P, Ghinamo L, Canil S, Durazzo M, Cassader M, Cavallo-Perin P. Is left ventricular hypertrophy a low-level inflammatory state? A population-based cohort study. Nutr Metab Cardiovasc Dis. 2012;22:668–76.

    Article  CAS  PubMed  Google Scholar 

  26. Satoh N, Shimatsu A, Kotani K, Sakane N, Yamada K, Suganami T, Kuzuya H, Ogawa Y. Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome. Diabetes Care. 2007;30:144–6.

    Article  CAS  PubMed  Google Scholar 

  27. Moertl D, Hammer A, Steiner S, Hutuleac R, Vonbank K, Berger R. Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study. Am Heart J. 2011;161(915):e1–9.

    PubMed  Google Scholar 

  28. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000;71:343S–8S.

    CAS  PubMed  Google Scholar 

  29. Sirbu A, Stanca I, Copaescu C, Martin S, Albu A, Barbu C, Fica S. Association of serum adiponectin and IGF-I levels with parameters of cardiac remodeling in severely obese patients. J Endocrinol Invest. 2013;36:686–92.

    Google Scholar 

  30. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinea in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. Endocrinol Med. 2001;86:1030–5.

    Google Scholar 

  31. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, Kawano H, Yano T, Aoe S, Takeya M, Shimatsu A, Kuzuya H, Kamei Y, Ogawa Y. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol. 2007;27:1918–25.

    Article  CAS  PubMed  Google Scholar 

  32. Domei T, Yokoi H, Kuramitsu S, Soga Y, Arita T, Ando K, Shirai S, Kondo K, Sakai K, Goya M, Iwabuchi M, Ueeda M, Nobuyoshi M. Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ J. 2012;76:423–9.

    Article  CAS  PubMed  Google Scholar 

  33. Dolecek TA, Grandis G. Dietary polyunsaturated fatty acids and mortality in multiple risk factor intervention trial (MRFIT). World Rev Nutr Diet. 1991;66:205–16.

    CAS  PubMed  Google Scholar 

  34. Kondo T, Ogawa K, Satake T, Kitazawa M, Taki K, Sugiyama S. Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor. Clin Cardiol. 1986;9:413–6.

    Article  CAS  PubMed  Google Scholar 

  35. Okuyama H. High n-6 to n-3 ratio of dietary fatty acids rather than serum cholesterol as a major risk factor for coronary heart disease. Eur J Lipid Sci Technol. 2001;103:418–22.

    Article  CAS  Google Scholar 

  36. Nakamura T, Azuma A, Kuribayashi T, Sugihara H, Okuda S, Nakagawa M. Serum fatty acid levels, dietary style and coronary heart disease in three neighbouring areas in Japan: the Kunihama study. Br J Nutr. 2003;89:267–72.

    Article  CAS  PubMed  Google Scholar 

  37. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K. Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet. 2007;369:1090–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

There were no relevant conflicts of interest to disclose in our study.

Author information

Authors and Affiliations

  1. Diabetes Center, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Kaya Okamoto, Asako Sato, Keiko Matsukawa, Takaomi Kasuga & Yasuko Uchigata

  2. Department of Clinical Laboratory, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Asako Sato

Authors
  1. Kaya Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Asako Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keiko Matsukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takaomi Kasuga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuko Uchigata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kaya Okamoto.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okamoto, K., Sato, A., Matsukawa, K. et al. Impact of eicosapentaenoic acid/arachidonic acid ratio on left ventricular structure in patients with diabetes. Diabetol Int 6, 46–54 (2015). https://doi.org/10.1007/s13340-014-0172-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13340-014-0172-0

Keywords

Search

Navigation