Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 8/2007

01-08-2007 | Meta-analysis

Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes

Authors: J. Hartweg, A. J. Farmer, R. Perera, R. R. Holman, H. A. W. Neil

Published in: Diabetologia | Issue 8/2007

Login to get access

Abstract

Aims/hypothesis

To determine the effects of marine-derived n-3 polyunsaturated fatty acids (PUFA) on established and emerging lipid and lipoprotein cardiovascular risk markers in patients with type 2 diabetes.

Materials and methods

We performed a systematic review and meta-analysis of randomised controlled trials comparing dietary or non-dietary intake of n-3 PUFA with placebo in patients with type 2 diabetes by searching databases from 1966 to December 2006. Changes in the following variables were recorded triacylglycerol; total cholesterol; HDL, LDL and VLDL and their subfractions; lipid ratios; apolipoproteins; and cholesterol particle sizes.

Results

There were 23 trials on non-dietary supplementation, involving 1,075 subjects with a mean treatment duration of 8.9 weeks, with sufficient data to permit pooling. Compared with placebo, n-3 PUFA had a statistically significant effect on four outcomes, reducing levels of (1) triacylglycerol (18 trials, 969 subjects) by 25% (mean 0.45 mmol/l; 95% CI −0.58 to −0.32; p < 0.00001); (2) VLDL-cholesterol (7 trials, 238 subjects) by 36% (0.07 mmol/l; 95% CI −0.13 to 0.00; p = 0.04); and (3) VLDL-triacylglycerol (6 trials, 178 subjects) by 39.7% (0.44 mmol/l; 95% CI −0.83 to −0.05; p = 0.03); while slightly increasing LDL (16 trials, 565 subjects) by 5.7% (0.11 mmol/l; 95% CI 0.00 to 0.22; p = 0.05). There were no significant effects on total cholesterol, apolipoproteins, lipid subfractions or ratios.

Conclusions/interpretation

In addition to recognised triacylglycerol-lowering effects, n-3 PUFA supplementation decreases VLDL-cholesterol and VLDL-triacylglycerol, but may have an adverse effect on LDL-cholesterol. Larger and longer term clinical trials are required to conclusively establish the effect of n-3 PUFA on cardiovascular risk markers and outcomes in type 2 diabetic patients.
Appendix
Available only for authorised users
Literature
1.
Bucher HC, Hengstler P, Schindler C, Meier G (2002) n-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 112:298–304PubMedCrossRef
2.
Burr ML, Ashfield-Watt PA, Dunstan FD et al (2003) Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr 57:193–200PubMedCrossRef
3.
Raitt MH, Connor WE, Morris C et al (2005) Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 293:2884–2891PubMedCrossRef
4.
Hooper L, Thompson RL, Harrison RA et al (2006) Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 332:752–760PubMedCrossRef
5.
Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE (2003) Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation 107:1852–1857PubMedCrossRef
6.
Das UN (2000) Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fat Acids 63:351–362CrossRef
7.
Erkkila AT, Lichtenstein AH, Mozaffarian D, Herrington DM (2004) Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr 80:626–632PubMed
8.
Manzella D, Barbieri M, Rizzo MR et al (2001) Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: effects of metabolic control. J Clin Endocrinol Metab 86:2769–2774PubMedCrossRef
9.
Farmer A, Montori V, Dinneen S, Clar C (2001) Fish oil in people with type 2 diabetes mellitus. Cochrane Database Syst Rev:CD003205
10.
Balk E, Chung M, Lichtenstein A et al (2004) Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease. Evidence Report/Technology Assessment No. 93. Agency for Healthcare Research and Quality, Tufts-New England Medical Center Evidence-based Practice Center, Rockville, MD
11.
Lewis A, Lookinland S, Beckstrand RL, Tiedeman ME (2004) Treatment of hypertriglyceridemia with omega-3 fatty acids: a systematic review. J Am Acad Nurse Pract 16:384–395PubMedCrossRef
12.
Frayn KN (2002) Insulin resistance, impaired postprandial lipid metabolism and abdominal obesity. A deadly triad. Med Princ Pract 11(Suppl 2):31–40PubMedCrossRef
13.
Mori TA, Burke V, Puddey IB et al (2000) Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 71:1085–1094PubMed
14.
Mori TA, Vandongen R, Masarei JR (1990) Fish oil-induced changes in apolipoproteins in IDDM subjects. Diabetes Care 13:725–732PubMedCrossRef
15.
Harris WS (1989) Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res 30:785–807PubMed
16.
Leigh-Firbank EC, Minihane AM, Leake DS et al (2002) Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr 87:435–445PubMedCrossRef
17.
Hartweg J, Farmer A, Holman R, Neil A (2007) Meta-analysis of the effects of omega-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes. Diabetologia 50:250–258PubMedCrossRef
18.
Dickersin K, Scherer R, Lefebvre C (1994) Identifying relevant studies for systematic reviews. BMJ 309:1286–1291PubMed
19.
Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12PubMedCrossRef
20.
Tramer MR, Reynolds DJ, Moore RA, McQuay HJ (1997) Impact of covert duplicate publication on meta-analysis: a case study. BMJ 315:635–640PubMed
21.
Rice JA (1995) Mathematical statistics and data analysis, 2nd ed. Duxbury, Belmont
22.
Alekseeva RI, Sharafetdinov K, Plotnikova OA, Meshcheriakova VA, Mal’tsev GI, Kulakova SN (2000) Effects of diet therapy including eiconol on clinical and metabolic parameters in patients with type 2 diabetes mellitus. Vopr Pitan 69:36–39 [Russian]PubMed
23.
Annuzzi G, Rivellese A, Capaldo B et al (1991) A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Atherosclerosis 87:65–73PubMedCrossRef
24.
Axelrod L, Camuso J, Williams E, Kleinman K, Briones E, Schoenfeld D (1994) Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. Diabetes Care 17:37–44PubMedCrossRef
25.
Boberg M, Pollare T, Siegbahn A, Vessby B (1992) Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 22:645–650PubMedCrossRef
26.
Borkman M, Chisholm DJ, Furler SM et al (1989) Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Diabetes 38:1314–1319PubMedCrossRef
27.
Brennan GM, McVeigh GE, Johnston GD, Hayes JR (1992) Dietary fish oil augments EDRF production or release in patients with non-insulin dependent diabetes mellitus [Abstract]. Br J Clin Pharmacol 33:531
28.
Connor WE, Prince MJ, Ullmann D et al (1993) The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Ann N Y Acad Sci 683:337–340PubMedCrossRef
29.
Goh YK, Jumpsen JA, Ryan EA, Clandinin MT (1997) Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients. Diabetologia 40:45–52PubMedCrossRef
30.
Hendra TJ, Britton ME, Roper DR et al (1990) Effects of fish oil supplements in NIDDM subjects. Controlled study. Diabetes Care 13:821–829PubMedCrossRef
31.
Jain S, Gaiha M, Bhattacharjee J, Anuradha S (2002) Effects of low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress––a prospective preliminary study. J Assoc Phys India 50:1028–1033
32.
Luo J, Rizkalla SW, Vidal H et al (1998) Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care 21:717–724PubMedCrossRef
33.
Maffettone A (1996) Long-term effects (six months) of omega-3 polyunsaturated fatty acids on insulin sensitivity and lipid metabolism in patients with type 2 diabetes and hypertriglyceridemia. G Ital Diabetol 16:185–193
34.
McGrath LT, Brennan GM, Donnelly JP, Johnston GD, Hayes JR, McVeigh GE (1996) Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus. Atherosclerosis 121:275–283PubMedCrossRef
35.
McManus RM, Jumpson J, Finegood DT, Clandinin MT, Ryan EA (1996) A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care 19:463–467PubMedCrossRef
36.
McVeigh GE, Brennan GM, Johnston GD et al (1993) Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36:33–38PubMedCrossRef
37.
McVeigh GE, Brennan GM, Cohn JN, Finkelstein SM, Hayes RJ, Johnston GD (1994) Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb 14:1425–1429PubMed
38.
Meshcheriakova VA., Plotnikova OA, Sharafetdinov KH, Alekseeva RI, Mal’tsev GI, Kulakova SN (2001) Comparative study of effects of diet therapy including eiconol or linseed oil on several parameters of lipid metabolism in patients with type 2 diabetes mellitus. Vopr Pitan 70:28–31PubMed
39.
Morgan WA, Raskin P, Rosenstock J (1995) A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM. Diabetes Care 18:83–86PubMedCrossRef
40.
Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin LJ (2003) Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 35:772–781PubMedCrossRef
41.
Mostad IL, Bjerve KS, Bjorgaas MR, Lydersen S, Grill V (2006) Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Am J Clin Nutr 84:540–550PubMed
42.
Patti L, Maffettone A, Iovine C et al (1999) Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia. Atherosclerosis 146:361–367PubMedCrossRef
43.
Pedersen H, Petersen M, Major-Pedersen A et al (2003) Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes. Eur J Clin Nutr 57:713–720PubMedCrossRef
44.
Pelikanova T, Kohout M, Valek J et al (1992) The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes. [Czech]. Cas Lek Ces 131:668–672
45.
Pelikanova T, Kohout M, Valek J, Kazdova L, Base J (1993) Metabolic effects of omega-3 fatty acids in type 2 (non-insulin-dependent) diabetic patients. Ann N Y Acad Sci 683:272–278PubMedCrossRef
46.
Petersen M, Pedersen H, Major-Pedersen A, Jensen T, Marckmann P (2002) Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. Diabetes Care 25:1704–1708PubMedCrossRef
47.
Puhakainen I, Ahola I, Yki-Jarvinen H (1995) Dietary supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. Am J Clin Nutr 61:121–126PubMed
48.
Rivellese AA, Maffettone A, Iovine C et al (1996) Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care 19:1207–1213PubMedCrossRef
49.
Schectman G, Kaul S, Kissebah AH (1988) Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 37:1567–1573PubMedCrossRef
50.
Silvis N, Vorster HH, Mollentze WF, Jager JD, Huisman HW (1988) Metabolic and haemostatic consequences of dietary fibre and n-3 fatty acids in black type 2 (NIDDM) diabetic subjects: a placebo controlled study. Int Clin Nutr Rev 10:362–380
51.
Sirtori CR, Paoletti R, Mancini M et al (1997) N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter Study. Am J Clin Nutr 65:1874–1881PubMed
52.
Vessby B, Boberg M (1990) Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. J Intern Med 228:165–171PubMedCrossRef
53.
Westerveld HT, de Graaf JC, van Breugel HH et al (1993) Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM. Diabetes Care 16:683–688PubMedCrossRef
54.
Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ (2002) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 76:1007–1015PubMed
55.
Woodman RJ, Mori TA, Burke V et al (2003) Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 166:85–93PubMedCrossRef
56.
Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE (1998) Fish oil and glycemic control in diabetes. A meta-analysis. Diabetes Care 21:494–500PubMedCrossRef
57.
Montori VM, Farmer A, Wollan PC, Dinneen SF (2000) Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care 23:1407–1415PubMedCrossRef
58.
Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC (2005) Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 165:725–730PubMedCrossRef
59.
Mensink RP, Katan MB (1992) Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb 12:911–919PubMed
60.
Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219PubMedCrossRef
61.
Sucic M, Katica D, Kovacevic V (1998) Effect of dietary fish supplementation on lipoprotein levels in patients with hyperlipoproteinemia. Coll Antropol 22:77–83PubMed
62.
Harris WS, Bulchandani D (2006) Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 17:387–393PubMedCrossRef
63.
Stacpoole PW, Alig J, Ammon L, Crockett SE (1989) Dose-response effects of dietary marine oil on carbohydrate and lipid metabolism in normal subjects and patients with hypertriglyceridemia. Metab Clin Exper 38:946–956
64.
Shidfar F, Keshavarz A, Jallali M, Miri R, Eshraghian M (2003) Comparison of the effects of simultaneous administration of vitamin C and omega-3 fatty acids on lipoproteins, apo A-I, apo B, and malondialdehyde in hyperlipidemic patients. Int J Vitam Nutr Res 73:163–170PubMedCrossRef
65.
Yusuf S, Hawken S, Ounpuu S et al (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–952PubMedCrossRef
66.
Natarajan S, Glick H, Criqui M, Horowitz D, Lipsitz SR, Kinosian B (2003) Cholesterol measures to identify and treat individuals at risk for coronary heart disease. Am J Prev Med 25:50–57PubMedCrossRef
67.
Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE (2005) Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA 294:326–333PubMedCrossRef
68.
Wang T, Gona P, Larson MG et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355:2631–2639
69.
70.
71.
72.
73.
Galan P, de Bree A, Mennen L et al (2003) Background and rationale of the SU.FOL.OM3 study: double-blind randomized placebo-controlled secondary prevention trial to test the impact of supplementation with folate, vitamin B6 and B12 and/or omega-3 fatty acids on the prevention of recurrent ischemic events in subjects with atherosclerosis in the coronary or cerebral arteries. J Nutr Health Aging 7:428–435PubMed
Metadata
Title
Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes
Authors
J. Hartweg
A. J. Farmer
R. Perera
R. R. Holman
H. A. W. Neil
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0695-z

Other articles of this Issue 8/2007

Diabetologia 8/2007 Go to the issue

Editorial

To boldly go—or to go too boldly? The accelerator hypothesis revisited

Article

Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual

Article

Single residue (K332A) substitution in Kir6.2 abolishes the stimulatory effect of long-chain acyl-CoA esters: indications for a long-chain acyl-CoA ester binding motif

Review

Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology

Short Communication

Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study

Article

Bivariate genome-wide scan for metabolic phenotypes in non-diabetic Chinese individuals from the Stanford, Asia and Pacific Program of Hypertension and Insulin Resistance Family Study

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits