Skip to main content
SpringerLink
Log in

EPA and Mixed Omega-3 Fatty Acids: Impact on Dyslipidemia and Cardiovascular Events in Patients with Diabetes

  • Chapter
  • First Online:
Lipoproteins in Diabetes Mellitus

Part of the book series: Contemporary Diabetes ((CDI))

  • 376 Accesses

Abstract

Diabetes is a global issue, affecting 537 million people worldwide and projected to reach 783 million by 2045. Patients with type 2 diabetes mellitus have up to a threefold increased risk for atherosclerotic cardiovascular disease (ASCVD). While statins help reduce this risk, residual risk persists. Elevated triglyceride levels contribute to residual CV risk and have been shown to be an independent risk factor for ASCVD. Prescription omega-3 fatty acids (OM3FAs) are approved to reduce elevated triglyceride levels, and in 2019, the highly purified eicosapentaenoic acid agent, icosapent ethyl, became the only OM3FA approved to reduce the risk of CV events in patients with established ASCVD or those with diabetes and at least two other risk factors. This chapter provides insight on the impact of OM3FAs on lipid levels, proposed mechanisms of action conferring cardioprotective effects, results of key clinical trials, and current guidelines for use of OM3FAs in patients with diabetes.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;3:1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Abdul-Ghani M, DeFronzo RA, Del Prato S, Chilton R, Singh R, Ryder REJ. Cardiovascular disease and type 2 diabetes: has the dawn of a new era arrived? Diabetes Care. 2017;40(7):813–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. IDF diabetes atlas. IDF diabetes atlas. 10th ed. Brussels, Belgium: International Diabetes Federation; 2021.

    Google Scholar 

  5. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Boren J, Catapano AL, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schofield JD, Liu Y, Rao-Balakrishna P, Malik RA, Soran H. Diabetes dyslipidemia. Diabetes Ther. 2016;7(2):203–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fruchart JC, Sacks FM, Hermans MP, Assmann G, Brown WV, Ceska R, et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. Diab Vasc Dis Res. 2008;5(4):319–35.

    Article  PubMed  Google Scholar 

  8. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35.

    Article  CAS  PubMed  Google Scholar 

  9. Morieri ML, Perrone V, Veronesi C, Degli Esposti L, Andretta M, Plebani M, et al. Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets’ attainment in subjects with and without type 2 diabetes. Cardiovasc Diabetol. 2021;20(1):144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased residual cardiovascular risk in patients with diabetes and high vs. normal triglycerides despite statin-controlled LDL cholesterol. Diabetes Obes Metab. 2019;21(2):366–71.

    Article  CAS  PubMed  Google Scholar 

  11. Fan W, Philip S, Granowitz C, Toth P, Wong N. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019;13:100–8.

    Article  PubMed  Google Scholar 

  12. Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.

    Article  CAS  PubMed  Google Scholar 

  13. The ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR III, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.

    Article  PubMed Central  Google Scholar 

  14. Gæde P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016;59(11):2298–307.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Reaven PD, Moritz TE, Schwenke DC, Anderson RJ, Criqui M, Detrano R, et al. Intensive glucose-lowering therapy reduces cardiovascular disease events in Veterans Affairs diabetes trial participants with lower calcified coronary atherosclerosis. Diabetes. 2009;58(11):2642–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.

    Article  CAS  PubMed  Google Scholar 

  17. Skulas-Ray AC, Wilson PWF, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140(12):e673–e91.

    Article  CAS  PubMed  Google Scholar 

  18. Lovaza. Lovaza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2020.

    Google Scholar 

  19. Vascepa. Vascepa [package insert]. Bridgewater, NJ: Amarin Pharma Inc.; 2019.

    Google Scholar 

  20. Omtryg. Omtryg [package insert]. Arlington, VA: Trygg Pharma, Inc.; 2014.

    Google Scholar 

  21. Epanova. Epanova [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

    Google Scholar 

  22. Bhatt DL, Steg G, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  23. Norris JM, Rich SS. Genetics of glucose homeostasis: implications for insulin resistance and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2012;32(9):2091–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Storlien LH, Kraegen EW, Chisholm DJ, Ford GL, Bruce DG, Pascoe WS. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science. 1987;237(4817):885–8.

    Article  CAS  PubMed  Google Scholar 

  25. Al Rijjal D, Liu Y, Lai M, Song Y, Danaei Z, Wu A, et al. Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired β-cell function. iScience. 2021;24(8):102909.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kalupahana NS, Claycombe K, Newman SJ, Stewart T, Siriwardhana N, Matthan N, et al. Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation. J Nutr. 2010;140(11):1915–22.

    Article  CAS  PubMed  Google Scholar 

  27. Kato T, Shimano H, Yamamoto T, Ishikawa M, Kumadaki S, Matsuzaka T, et al. Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. Diabetes. 2008;57(9):2382–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vessby B, Boberg M. Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. J Intern Med. 1990;228(2):165–71.

    Article  CAS  PubMed  Google Scholar 

  29. Schectman G, Kaul S, Kissebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes. 1988;37(11):1567–73.

    Article  CAS  PubMed  Google Scholar 

  30. Hendra TJ, Britton ME, Roper DR, Wagaine-Twabwe D, Jeremy JY, Dandona P, et al. Effects of fish oil supplements in NIDDM subjects. Controlled study. Diabetes Care. 1990;13(8):821–9.

    Article  CAS  PubMed  Google Scholar 

  31. Holness MJ, Smith ND, Greenwood GK, Sugden MC. Acute omega-3 fatty acid enrichment selectively reverses high-saturated fat feeding-induced insulin hypersecretion but does not improve peripheral insulin resistance. Diabetes. 2004;53(Suppl 1):S166–71.

    Article  CAS  PubMed  Google Scholar 

  32. Friday KE, Childs MT, Tsunehara CH, Fujimoto WY, Bierman EL, Ensinck JW. Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation in type II diabetes. Diabetes Care. 1989;12(4):276–81.

    Article  CAS  PubMed  Google Scholar 

  33. Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1988;108(5):663–8.

    Article  CAS  PubMed  Google Scholar 

  34. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110(7):984–92.

    Article  CAS  PubMed  Google Scholar 

  35. Oikawa S, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, et al. 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(2):535–9.

    Article  CAS  PubMed  Google Scholar 

  36. Bhatt DL, Brinton EA, Miller M, Steg G, Jacobson TA, Ketchum SB, et al. Icosapent ethyl provides consistent cardiovascular benefit in patients with diabetes in REDUCE-IT [presentation]. Annual Scientific Sessions of the American Diabetes Association; 2020.

    Google Scholar 

  37. Wang JF, Zhang HM, Li YY, Xia S, Wei Y, Yang L, et al. A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial. Lipids Health Dis. 2019;18(1):106.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bays HE, Braeckman RA, Ballantyne CM, Kastelein JJ, Otvos JD, Stirtan WG, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). J Clin Lipidol. 2012;6(6):565–72.

    Article  PubMed  Google Scholar 

  39. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8.

    Article  CAS  PubMed  Google Scholar 

  40. Brinton EA, Ballantyne CM, Bays HE, Kastelein JJ, Braeckman RA, Soni PN. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study. Cardiovasc Diabetol. 2013;12(1):100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen C, Yu X, Shao S. Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS One. 2015;10(10):e0139565.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gao H, Geng T, Huang T, Zhao Q. Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis. Lipids Health Dis. 2017;16(1):131.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Akinkuolie AO, Ngwa JS, Meigs JB, Djousse L. Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials. Clin Nutr. 2011;30(6):702–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Qian F, Ardisson Korat AV, Imamura F, Marklund M, Tintle N, Virtanen JK, et al. n-3 Fatty acid biomarkers and incident type 2 diabetes: an individual participant-level pooling project of 20 prospective cohort studies. Diabetes Care. 2021;44(5):1133–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lalia AZ, Lanza IR. Insulin-sensitizing effects of omega-3 fatty acids: lost in translation? Nutrients. 2016;8(6):329.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Li D. Omega-3 polyunsaturated fatty acids and non-communicable diseases: meta-analysis based systematic review. Asia Pac J Clin Nutr. 2015;24(1):10–5.

    PubMed  Google Scholar 

  47. Flachs P, Rossmeisl M, Kopecky J. The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity. Physiol Res. 2014;63(Suppl 1):S93–118.

    Article  CAS  PubMed  Google Scholar 

  48. Innes JK, Calder PC. The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiometabolic risk factors: a systematic review. Int J Mol Sci. 2018;19(2):532.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. P T. 2013;38(11):681–91.

    PubMed  PubMed Central  Google Scholar 

  50. Ito MK. A comparative overview of prescription omega-3 fatty acid products. P T. 2015;40(12):826–57.

    PubMed  PubMed Central  Google Scholar 

  51. Oscarsson J, Hurt-Camejo E. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review. Lipids Health Dis. 2017;16(1):149.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Tajuddin N, Shaikh A, Hassan A. Prescription omega-3 fatty acid products: considerations for patients with diabetes mellitus. Diabetes Metab Syndr Obes. 2016;9:109–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Peng J, Luo F, Ruan G, Peng R, Li X. Hypertriglyceridemia and atherosclerosis. Lipids Health Dis. 2017;16(1):233.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Backes J, Anzalone D, Hilleman D, Catini J. The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis. 2016;15(1):118.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Nelson JR, Budoff MJ, Wani OR, Le V, Patel DK, Nelson A, et al. EPA’s pleiotropic mechanisms of action: a narrative review. Postgrad Med. 2021;133(6):651–64.

    Article  PubMed  Google Scholar 

  56. Shearer GC, Savinova OV, Harris WS. Fish oil—how does it reduce plasma triglycerides? Biochim Biophys Acta. 2012;1821(5):843–51.

    Article  CAS  PubMed  Google Scholar 

  57. GISSI Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354(9177):447–55.

    Article  Google Scholar 

  58. ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, et al. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379(16):1540–50.

    Article  Google Scholar 

  59. Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation. 2010;122(21):2152–9.

    Article  CAS  PubMed  Google Scholar 

  60. Kromhout D, Giltay EJ, Geleijnse JM. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–26.

    Article  CAS  PubMed  Google Scholar 

  61. ORIGIN Trial Investigators. n-3 Fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367(4):309–18.

    Article  Google Scholar 

  62. The Risk and Prevention Study Collaborative Group. n-3 Fatty acids in patients with multiple cardiovascular risk factors: the Risk and Prevention Study Collaborative Group. N Engl J Med. 2013;368:1800–8.

    Article  Google Scholar 

  63. Kalstad AA, Myhre PL, Laake K, Tveit SH, Schmidt EB, Smith P, et al. Effects of n-3 fatty acid supplements in elderly patients after myocardial infarction: a randomized controlled trial. Circulation. 2020;143(6):528–39.

    Article  PubMed  Google Scholar 

  64. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32.

    Article  CAS  PubMed  Google Scholar 

  65. Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135–40.

    Article  CAS  PubMed  Google Scholar 

  67. FDA. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups [news release]. U.S. Food and Drug Administration; 2019. https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups.

  68. Bhatt DL, Brinton EA, Steg PG, Ketchum SB, Juliano RA, Jiao L, et al. Substantial cardiovascular risk reduction with icosapent ethyl regardless of diabetes status or BMI: REDUCE-IT BMI [abstract 256-OR]. Diabetes. 2021;70(Suppl 1):256-OR.

    Article  Google Scholar 

  69. Daida H, Nishizaki Y, Iwata H, Inoue T, Hirayama A, Kimura K, et al. Randomized trial for evaluation in secondary prevention efficacy of combination therapy - statin and eicosapentaenoic acid (RESPECT-EPA) [oral presentation]. Chicago: IL. Annual Scientific Sessions of the American Heart Association; 2022.

    Google Scholar 

  70. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, et al. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb. 2011;18(2):99–107.

    Google Scholar 

  71. Bhatt DL, Miller M, Steg G, Brinton EA, Jacobson TA, Ketchum SB, et al. EPA levels and cardiovascular outcomes in the reduction of cardiovascular events with icosapent ethyl-intervention trial [oral presentation]. Chicago: IL. Annual Scientific Session of the American College of Cardiology; 2020.

    Google Scholar 

  72. Sherratt SCR, Lero M, Mason RP. Are dietary fish oil supplements appropriate for dyslipidemia management? A review of the evidence. Curr Opin Lipidol. 2020;31(2):94–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chatzopoulou S, Eriksson NL, Eriksson D. Improving risk assessment in the European Food Safety Authority: lessons from the European Medicines Agency. Front Plant Sci. 2020;11:349.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Albert BB, Derraik JG, Cameron-Smith D, Hofman PL, Tumanov S, Villas-Boas SG, et al. Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA. Sci Rep. 2015;5:7928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mason RP, Libby P, Bhatt DL. Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid. Arterioscler Thromb Vasc Biol. 2020;40(5):1135–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Suvarna R, Rao SS, Joshi C, Kedage V, Muttigi MS, Shetty JK, et al. Paraoxonase activity In type 2 diabetes mellitus patients with and without complications. J Clin Diagn Res. 2011;5(1):63–5.

    CAS  Google Scholar 

  77. Golzari MH, Hosseini S, Koohdani F, Saboor Yaraghi AA, Javanbakht MH, Mohammadzadeh-Honarvar N, et al. The effect of eicosapentaenoic acid on the serum levels and enzymatic activity of paraoxonase 1 in the patients with type 2 diabetes mellitus. Acta Med Iran. 2017;55(8):486–95.

    PubMed  Google Scholar 

  78. Golzari MH, Javanbakht MH, Ghaedi E, Mohammadi H, Djalali M. Effect of eicosapentaenoic acid supplementation on paraoxonase 2 gene expression in patients with type 2 diabetes mellitus: a randomized double-blind clinical trial. Clin Nutr Res. 2019;8(1):17–27.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Sherratt SCR, Libby P, Bhatt DL, Mason RP. Comparative effects of mineral oil, corn oil, eicosapentaenoic acid, and docosahexaenoic acid in an in vitro atherosclerosis model. J Am Heart Assoc. 2023;12:e029109.

    Google Scholar 

  80. Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7):514–25.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421–6.

    Article  CAS  PubMed  Google Scholar 

  82. Hong YJ, Jeong MH, Choi YH, Song JA, Ahmed K, Kim DH, et al. Relationship between microalbuminuria and vulnerable plaque components in patients with acute coronary syndrome and with diabetes mellitus. Virtual histology-intravascular ultrasound. Circ J. 2011;75(12):2893–901.

    Article  PubMed  Google Scholar 

  83. Lee CC, Sharp SJ, Wexler DJ, Adler AI. Dietary intake of eicosapentaenoic and docosahexaenoic acid and diabetic nephropathy: cohort analysis of the diabetes control and complications trial. Diabetes Care. 2010;33(7):1454–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Han E, Yun Y, Kim G, Lee YH, Wang HJ, Lee BW, et al. Effects of omega-3 fatty acid supplementation on diabetic nephropathy progression in patients with diabetes and hypertriglyceridemia. PLoS One. 2016;11(5):e0154683.

    Article  PubMed  PubMed Central  Google Scholar 

  85. DiNicolantonio JJ, O’Keefe JH. The benefits of omega-3 fats for stabilizing and remodeling atherosclerosis. Mo Med. 2020;117(1):65–9.

    PubMed  PubMed Central  Google Scholar 

  86. Yahagi K, Kolodgie FD, Lutter C, Mori H, Romero ME, Finn AV, et al. Pathology of human coronary and carotid artery atherosclerosis and vascular calcification in diabetes mellitus. Arterioscler Thromb Vasc Biol. 2017;37(2):191–204.

    Article  CAS  PubMed  Google Scholar 

  87. Kim U, Leipsic JA, Sellers SL, Shao M, Blanke P, Hadamitzky M, et al. Natural history of diabetic coronary atherosclerosis by quantitative measurement of serial coronary computed tomographic angiography: results of the PARADIGM study. JACC Cardiovasc Imaging. 2018;11(10):1461–71.

    Article  PubMed  Google Scholar 

  88. Nakanishi R, Ceponiene I, Osawa K, Luo Y, Kanisawa M, Megowan N, et al. Plaque progression assessed by a novel semi-automated quantitative plaque software on coronary computed tomography angiography between diabetes and non-diabetes patients: a propensity-score matching study. Atherosclerosis. 2016;255:73–9.

    Article  CAS  PubMed  Google Scholar 

  89. Sugiyama T, Yamamoto E, Bryniarski K, Xing L, Fracassi F, Lee H, et al. Coronary plaque characteristics in patients with diabetes mellitus who presented with acute coronary syndromes. J Am Heart Assoc. 2018;7(14):e009245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mita T, Watada H, Ogihara T, Nomiyama T, Ogawa O, Kinoshita J, et al. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes. Atherosclerosis. 2007;191(1):162–7.

    Article  CAS  PubMed  Google Scholar 

  91. Katoh A, Ikeda H. Daily intake of eicosapentaenoic acid inhibits the progression of carotid intimal-media thickness in patients with dyslipidemia [in Japanese]. Ther Res. 2011;32(6):863–8.

    Google Scholar 

  92. Budoff MJ, Bhatt DL, Kinninger A, Lakshmanan S, Muhlestein JB, Le VT, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J. 2020;41(40):3925–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Watanabe T, Ando K, Daidoji H, Otaki Y, Sugawara S, Matsui M, et al. A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins. J Cardiol. 2017;70(6):537–44.

    Article  PubMed  Google Scholar 

  94. Niki T, Wakatsuki T, Yamaguchi K, Taketani Y, Oeduka H, Kusunose K, et al. Effects of the addition of eicosapentaenoic acid to strong statin therapy on inflammatory cytokines and coronary plaque components assessed by integrated backscatter intravascular ultrasound. Circ J. 2016;80(2):450–60.

    Article  CAS  PubMed  Google Scholar 

  95. Costantini L, Molinari R, Farinon B, Merendino N. Impact of omega-3 fatty acids on the gut microbiota. Int J Mol Sci. 2017;18(12):2645.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Menni C, Zierer J, Pallister T, Jackson MA, Long T, Mohney RP, et al. Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women. Sci Rep. 2017;7(1):11079.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Fu Y, Wang Y, Gao H, Li D, Jiang R, Ge L, et al. Associations among dietary omega-3 polyunsaturated fatty acids, the gut microbiota, and intestinal immunity. Mediat Inflamm. 2021;2021:8879227.

    Article  Google Scholar 

  98. Bidu C, Escoula Q, Bellenger S, Spor A, Galan M, Geissler A, et al. The transplantation of ω3 PUFA-altered gut microbiota of fat-1 mice to wild-type littermates prevents obesity and associated metabolic disorders. Diabetes. 2018;67(8):1512–23.

    Article  CAS  PubMed  Google Scholar 

  99. Zhuang P, Li H, Jia W, Shou Q, Zhu Y, Mao L, et al. Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice. Microbiome. 2021;9(1):185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Balfegó M, Canivell S, Hanzu FA, Sala-Vila A, Martínez-Medina M, Murillo S, et al. Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial. Lipids Health Dis. 2016;15:78.

    Article  PubMed  PubMed Central  Google Scholar 

  101. American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S111–s34.

    Article  Google Scholar 

  102. American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S125–s50.

    Article  Google Scholar 

  103. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J. 2020;41(2):255–323.

    Article  PubMed  Google Scholar 

  104. Virani SS, Morris PB, Agarwala A, Ballantyne CM, Birtcher KK, Kris-Etherton PM, et al. 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;8(9):960–93.

    Article  Google Scholar 

  105. Orringer CE, Jacobson TA, Maki KC. National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk. J Clin Lipidol. 2019;13(6):860–72.

    Article  PubMed  Google Scholar 

  106. Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2020 executive summary. Endocr Pract. 2020;26(1):107–39.

    Article  PubMed  Google Scholar 

  107. Arnold SV, Bhatt DL, Barsness GW, Beatty AL, Deedwania PC, Inzucchi SE, et al. Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association. Circulation. 2020;141(19):e779–806.

    Article  PubMed  Google Scholar 

  108. Handelsman Y, Jellinger PS, Guerin CK, Bloomgarden ZT, Brinton EA, Budoff MJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm—2020 executive summary. Endocr Pract. 2020;26(10):1196–224.

    Article  PubMed  Google Scholar 

  109. Newman CB, Blaha MJ, Boord JB, Cariou B, Chait A, Fein HG, et al. Lipid management in patients with endocrine disorders: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2020;105(12):3613–82.

    Article  Google Scholar 

  110. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364–467.

    Article  PubMed  Google Scholar 

  111. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111–88.

    Article  PubMed  Google Scholar 

  112. Pearson GJ, Thanassoulis G, Anderson TJ, Barry AR, Couture P, Dayan N, et al. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2021;37(8):1129–50.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Amarin Pharma, Inc., Bridgewater, NJ, USA.

Author information

Authors and Affiliations

  1. Clinical Research and Adult Diabetes sections, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA, USA

    Om P. Ganda

  2. Department of Medicine, Community Endocrine Group, Albany Medical Center, Albany, NY, USA

    Robert Busch

  3. California Cardiovascular Institute, Fresno, CA, USA

    J. R. Nelson

  4. Medical Affairs, Amarin Pharma, Inc., Bridgewater, NJ, USA

    Sephy Philip

Authors
  1. Om P. Ganda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Busch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. R. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sephy Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sephy Philip .

Editor information

Editors and Affiliations

  1. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    Alicia J. Jenkins

  2. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Peter P. Toth

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ganda, O.P., Busch, R., Nelson, J.R., Philip, S. (2023). EPA and Mixed Omega-3 Fatty Acids: Impact on Dyslipidemia and Cardiovascular Events in Patients with Diabetes. In: Jenkins, A.J., Toth, P.P. (eds) Lipoproteins in Diabetes Mellitus. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-031-26681-2_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-26681-2_25

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-031-26680-5

  • Online ISBN: 978-3-031-26681-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation