Department of Pharmacology and Toxicology, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
Copyright © 2018 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.
Reference | Sample size, % female subjects | Age, yr | BMI, kg/m2 | Duration, design | Disease, medication | Intervention (daily EPA/DHA dose) | Control group | Outcome, parameters |
---|---|---|---|---|---|---|---|---|
Hashemi et al. (2014) [30] | 70 (I: 41, C: 36) | I: 44±5.0 | I: 27.9±1.7 | 12 Weeks, parallel | T2DM subjects; treated with biguanides and sulfonylureas (76%), sulfonylureas (16%) or biguanides alone (8%) | EPA pearls (2,000 mg) | Placebo (corn oil) | Adiponectin |
C: 45±4.1 | C: 27.8±1.6 | |||||||
Jacobo-Cejudo et al. (2017) [31] | 54 (I: 70.6, C: 83.9) | I: 50.4±6.3 | I: 25.6±2.4 | 24 Weeks, parallel | T2DM; therapy with glibenclamide+metformin or metformin alone, received no additional dietary or lifestyle advice | Fish oil (320 mg EPA, 200 mg DHA) | Placebo (cornstarch) | Adiponectin, leptin, resistin |
C: 48.1±6.9 | C: 26.0±1.6 | |||||||
Kabir et al. (2007) [32] | 26 (all female) | I: 55±2.0 | 30±2.0 in both groups | 2 Months, parallel | Postmenopausal T2DM women without hypertriglyceridemia; 3 patients treated only with diet, 23 taking oral hypoglycemic treatment (7 only biguanides, 16 sulfonylureas and biguanides), 5 lipid-lowering agents, 6 hormone replacement therapy | Fish oil (1,080 mg EPA, 720 mg DHA) | Placebo (paraffin oil) | Adiponectin, leptin, TNF-α, IL-6, PAI-1 |
C: 55±1.0 | ||||||||
Krebs et al. (2006) [33] | 67 (all female) | 44.7±13.2 | 35.0±5.5 | 24 Weeks, parallel | Overweight or obese women with hyperinsulinemia | Fish oil (1,300 mg EPA, 2,900 mg DHA)+weight loss intervention (10% of body weight loss in 12 weeks, 12 weeks weight maintenance) | 5 g oil/day totaling 2.8 g linoleic acid and 1.4 g oleic acid+weight loss intervention (10% of body weight loss in 12 weeks, 12 weeks weight maintenance) | Adiponectin, leptin, TNF-α, IL-6 |
Lee et al. (2014) [34] | 37 (I: 62.5, C: 71.4) | I: 56.2±8.7 | I: 33.2±4.8 | 8 Weeks, parallel | Early stage T2DM (no evidence of end-stage organ damage secondary to diabetes) | Fish oil (3,580 mg EPA, 2,440 mg DHA) | Placebo (corn oil) | Leptin |
C: 59.9±9.8 | C: 34.8±5.3 | |||||||
Mazaherioun et al. (2017) [35] | 85 (I: 34.09, C: 41.4) | I: 51.5±7.45 | I: 29.22±3.58 | 10 Weeks, parallel | T2DM; no insulin, thiazolidinediones or anti-obesity medications | Omega-3 capsules (1,800 mg EPA, 900 mg DHA) | Placebo (paraffin) | Adiponectin |
C: 50.56±7.21 | C: 29.21±2.90 | |||||||
Mocking et al. (2012) [36] | 24 (I: 62, C: 42) | I: 53.1±13.8 | I: 29.3±5.1 | 12 Weeks, parallel | Diabetic patients with major depressive disorder (determined by the Composite International Diagnostic Interview standards); therapy with antidepressants for at least 2 months, diabetes treated with diet only, hypoglycemics, insulin, or both | Fish oil (at least 900 mg ethyl-EPA) | Placebo (rapeseed oil+medium chain triglycerides) | TNF-α, IL-6 |
C: 55.0±8.6 | C: 29.8±4.8 | |||||||
Malekshahi Moghadam et al. (2012) [37] | 84 (50% in both groups) | I: 55.36±9.88 | I: 27.72±3.47 | 8 Weeks, parallel | T2DM subjects (at least 2 years since diagnosis), all receiving anti-hyperglycemic treatment | Omega-3 capsules (1,548 mg EPA, 828 mg DHA) | Placebo (sunflower oil) | TNF-α |
C: 52.96±10.72 | C: 27.51±3.16 | |||||||
Mori et al. (2003) [38]a | 51 (I1: 17,6, I2: 27,7, C: 25) | I1: 61.2±2.3 | I1: 30.6±0.7 | 6 Weeks, parallel | Non-smoking, treated-hypertensive, T2DM men and postmenopausal women; antihypertensive therapy for a minimum of 3 months, oral hypoglycemic, but no insulin therapy | I1: 4 g EPA-capsules per day (96% EPA ethyl ester) | Placebo (olive oil) | TNF-α, IL-6 |
I2: 60.9±1.9 | I2: 27.9±0.8 | I2: 4 g DHA per day (92% DHA ethyl ester) | ||||||
C: 61.5±1.9 | C: 29.9±1.0 | |||||||
Ogawa et al. (2013) [39] | 26 (I: 69, C: 82) | I: 79.5±8.6 | I: 19.9±4.0 | 3 Mllel | Bedridden elderly T2DM patients | Liquid diet rich in EPA (25 mg/100 kcal) and DHA (17 mg/100 kcal)b | Liquid diet lacking EPA and DHA | Adiponectin, TNF-α, IL-6 |
C: 81.2±7.6 | C: 20.1±3.6 | |||||||
Poreba et al. (2017) [40] | 74 (I: 38,9, C: 31.6) | I: 64.4±6.7 | I: 30.9 (27.9–34.7) | 3 Months, parallel | T2DM patients with a history of coronary artery disease or peripheral artery disease | Omega-3 drink (1,000 mg EPA, 1,000 mg DHA) | Drink without omega-3 | Adiponectin, leptin, TNF-α, IL-6 |
C: 66.7±6.8 | C: 31.1 (28.1–32.7)c | |||||||
Spencer et al. (2013) [41] | 33 (I: 68,4, C: 64,2) | I: 48.8±2.3 | I: 33.4±2.3 | 12 Weeks, parallel | Non-diabetic subjects with either impaired fasting glucose, impaired glucose tolerance (23 subjects), or at least three signs of metabolic syndrome | Fish oil (1,860 mg EPA, 1,500 mg DHA) | Placebo (corn oil) | Adiponectin, leptin, TNF-α, IL-6, PAI-1, resistin |
C: 53.3±2.2 | C: 33.4±1.1 | |||||||
Stirban et al. (2014) [42] | 34, No specification of sex | 56.8±8.3 | 31.2±4.1 | 6 Weeks, cross-over | T2DM (duration 9.8± 6.6 years), no history of major cardiovascular events or a surgical or interventional history within the previous 6 months; treated with low dose aspirin (n=20), ACE-inhibitors or AR blockers (n=24), calcium channel blockers (n=5), β-blockers (n=15), diuretics (n=13), and statins (n=13), all withdrawn before measurements; diabetes medication: diet (n=3), oral therapy (n=16), insulin (n=4), oral hypoglycemic plus insulin (n=10), and incretin mimetics (n=1) | Omega-3 capsules (920 mg EPA, 760 mg DHA) | Placebo (olive oil) | Adiponectin, leptin |
Veleba et al. (2015) [43] | 29, 34 | I: 59.5 | I: 34.0 | 24 Weeks, parallel | T2DM (at least 3 months from diagnosis); metformin as monotherapy as a stable dose (0.5–3.0 g/day) for at least 1 month | Omega-3 concentrate (750 mg EPA, 2,000 mg DHA) | Placebo (corn oil) | Adiponectin, leptin |
C: 62.0 | C: 30.9 | |||||||
Wong et al. (2013) [44] | 25, 44 | 60±4.0 | I: 34±2.0 | 16 Weeks, parallel | Middle-aged, centrally obese, normotensive, dyslipidemic (elevated triglycerides, low HDL), insulin resistant adults; 6 subjects receiving lipid-lowering therapy (4 atorvastatin, 2 rosuvastatin), 5 anti-hypertensive treatment (2 on ACE inhibitors, 2 on AR blockers, 1 on β1-blocker) | Fish oil (1,840 mg EPA-ethyl ester, 1,520 mg ethyl-ester)+weight loss intervention (12 weeks hypocaloric diet with energy deficit of at least 1,900 kJ/day, followed by 4 weeks of weight maintenance with energy intake increased by 460 kJ/day) | Weight loss alone (protocol as in intervention group) | Adiponectin |
C: 33±1.0 |
Values are presented as mean±standard deviation.
BMI, body mass index; I, intervention group; C, control group; T2DM, type 2 diabetic mellitus; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; TNF-α, tumor necrosis factor α; IL-6, interleuk in 6; PAI-1, plasminogen-activator inhibitor 1; ACE, angiotensin-converting-enzyme; AR, angiotensin II receptor; HDL, high density lipoprotein.
aEPA and DHA were used in two separate treatment arms, bThe patients consumed 1,015.4±231.1 kcal/day, cValues are presented as median (interquartile range).
Reference | Sample size, % female subjects | Age, yr | BMI, kg/m2 | Duration, design | Disease, medication | Intervention (daily EPA/DHA dose) | Control group | Outcome, parameters |
---|---|---|---|---|---|---|---|---|
Hashemi et al. (2014) [ | 70 (I: 41, C: 36) | I: 44±5.0 | I: 27.9±1.7 | 12 Weeks, parallel | T2DM subjects; treated with biguanides and sulfonylureas (76%), sulfonylureas (16%) or biguanides alone (8%) | EPA pearls (2,000 mg) | Placebo (corn oil) | Adiponectin |
C: 45±4.1 | C: 27.8±1.6 | |||||||
Jacobo-Cejudo et al. (2017) [ | 54 (I: 70.6, C: 83.9) | I: 50.4±6.3 | I: 25.6±2.4 | 24 Weeks, parallel | T2DM; therapy with glibenclamide+metformin or metformin alone, received no additional dietary or lifestyle advice | Fish oil (320 mg EPA, 200 mg DHA) | Placebo (cornstarch) | Adiponectin, leptin, resistin |
C: 48.1±6.9 | C: 26.0±1.6 | |||||||
Kabir et al. (2007) [ | 26 (all female) | I: 55±2.0 | 30±2.0 in both groups | 2 Months, parallel | Postmenopausal T2DM women without hypertriglyceridemia; 3 patients treated only with diet, 23 taking oral hypoglycemic treatment (7 only biguanides, 16 sulfonylureas and biguanides), 5 lipid-lowering agents, 6 hormone replacement therapy | Fish oil (1,080 mg EPA, 720 mg DHA) | Placebo (paraffin oil) | Adiponectin, leptin, TNF-α, IL-6, PAI-1 |
C: 55±1.0 | ||||||||
Krebs et al. (2006) [ | 67 (all female) | 44.7±13.2 | 35.0±5.5 | 24 Weeks, parallel | Overweight or obese women with hyperinsulinemia | Fish oil (1,300 mg EPA, 2,900 mg DHA)+weight loss intervention (10% of body weight loss in 12 weeks, 12 weeks weight maintenance) | 5 g oil/day totaling 2.8 g linoleic acid and 1.4 g oleic acid+weight loss intervention (10% of body weight loss in 12 weeks, 12 weeks weight maintenance) | Adiponectin, leptin, TNF-α, IL-6 |
Lee et al. (2014) [ | 37 (I: 62.5, C: 71.4) | I: 56.2±8.7 | I: 33.2±4.8 | 8 Weeks, parallel | Early stage T2DM (no evidence of end-stage organ damage secondary to diabetes) | Fish oil (3,580 mg EPA, 2,440 mg DHA) | Placebo (corn oil) | Leptin |
C: 59.9±9.8 | C: 34.8±5.3 | |||||||
Mazaherioun et al. (2017) [ | 85 (I: 34.09, C: 41.4) | I: 51.5±7.45 | I: 29.22±3.58 | 10 Weeks, parallel | T2DM; no insulin, thiazolidinediones or anti-obesity medications | Omega-3 capsules (1,800 mg EPA, 900 mg DHA) | Placebo (paraffin) | Adiponectin |
C: 50.56±7.21 | C: 29.21±2.90 | |||||||
Mocking et al. (2012) [ | 24 (I: 62, C: 42) | I: 53.1±13.8 | I: 29.3±5.1 | 12 Weeks, parallel | Diabetic patients with major depressive disorder (determined by the Composite International Diagnostic Interview standards); therapy with antidepressants for at least 2 months, diabetes treated with diet only, hypoglycemics, insulin, or both | Fish oil (at least 900 mg ethyl-EPA) | Placebo (rapeseed oil+medium chain triglycerides) | TNF-α, IL-6 |
C: 55.0±8.6 | C: 29.8±4.8 | |||||||
Malekshahi Moghadam et al. (2012) [ | 84 (50% in both groups) | I: 55.36±9.88 | I: 27.72±3.47 | 8 Weeks, parallel | T2DM subjects (at least 2 years since diagnosis), all receiving anti-hyperglycemic treatment | Omega-3 capsules (1,548 mg EPA, 828 mg DHA) | Placebo (sunflower oil) | TNF-α |
C: 52.96±10.72 | C: 27.51±3.16 | |||||||
Mori et al. (2003) [ | 51 (I1: 17,6, I2: 27,7, C: 25) | I1: 61.2±2.3 | I1: 30.6±0.7 | 6 Weeks, parallel | Non-smoking, treated-hypertensive, T2DM men and postmenopausal women; antihypertensive therapy for a minimum of 3 months, oral hypoglycemic, but no insulin therapy | I1: 4 g EPA-capsules per day (96% EPA ethyl ester) | Placebo (olive oil) | TNF-α, IL-6 |
I2: 60.9±1.9 | I2: 27.9±0.8 | I2: 4 g DHA per day (92% DHA ethyl ester) | ||||||
C: 61.5±1.9 | C: 29.9±1.0 | |||||||
Ogawa et al. (2013) [ | 26 (I: 69, C: 82) | I: 79.5±8.6 | I: 19.9±4.0 | 3 Mllel | Bedridden elderly T2DM patients | Liquid diet rich in EPA (25 mg/100 kcal) and DHA (17 mg/100 kcal)b | Liquid diet lacking EPA and DHA | Adiponectin, TNF-α, IL-6 |
C: 81.2±7.6 | C: 20.1±3.6 | |||||||
Poreba et al. (2017) [ | 74 (I: 38,9, C: 31.6) | I: 64.4±6.7 | I: 30.9 (27.9–34.7) | 3 Months, parallel | T2DM patients with a history of coronary artery disease or peripheral artery disease | Omega-3 drink (1,000 mg EPA, 1,000 mg DHA) | Drink without omega-3 | Adiponectin, leptin, TNF-α, IL-6 |
C: 66.7±6.8 | C: 31.1 (28.1–32.7)c | |||||||
Spencer et al. (2013) [ | 33 (I: 68,4, C: 64,2) | I: 48.8±2.3 | I: 33.4±2.3 | 12 Weeks, parallel | Non-diabetic subjects with either impaired fasting glucose, impaired glucose tolerance (23 subjects), or at least three signs of metabolic syndrome | Fish oil (1,860 mg EPA, 1,500 mg DHA) | Placebo (corn oil) | Adiponectin, leptin, TNF-α, IL-6, PAI-1, resistin |
C: 53.3±2.2 | C: 33.4±1.1 | |||||||
Stirban et al. (2014) [ | 34, No specification of sex | 56.8±8.3 | 31.2±4.1 | 6 Weeks, cross-over | T2DM (duration 9.8± 6.6 years), no history of major cardiovascular events or a surgical or interventional history within the previous 6 months; treated with low dose aspirin (n=20), ACE-inhibitors or AR blockers (n=24), calcium channel blockers (n=5), β-blockers (n=15), diuretics (n=13), and statins (n=13), all withdrawn before measurements; diabetes medication: diet (n=3), oral therapy (n=16), insulin (n=4), oral hypoglycemic plus insulin (n=10), and incretin mimetics (n=1) | Omega-3 capsules (920 mg EPA, 760 mg DHA) | Placebo (olive oil) | Adiponectin, leptin |
Veleba et al. (2015) [ | 29, 34 | I: 59.5 | I: 34.0 | 24 Weeks, parallel | T2DM (at least 3 months from diagnosis); metformin as monotherapy as a stable dose (0.5–3.0 g/day) for at least 1 month | Omega-3 concentrate (750 mg EPA, 2,000 mg DHA) | Placebo (corn oil) | Adiponectin, leptin |
C: 62.0 | C: 30.9 | |||||||
Wong et al. (2013) [ | 25, 44 | 60±4.0 | I: 34±2.0 | 16 Weeks, parallel | Middle-aged, centrally obese, normotensive, dyslipidemic (elevated triglycerides, low HDL), insulin resistant adults; 6 subjects receiving lipid-lowering therapy (4 atorvastatin, 2 rosuvastatin), 5 anti-hypertensive treatment (2 on ACE inhibitors, 2 on AR blockers, 1 on β1-blocker) | Fish oil (1,840 mg EPA-ethyl ester, 1,520 mg ethyl-ester)+weight loss intervention (12 weeks hypocaloric diet with energy deficit of at least 1,900 kJ/day, followed by 4 weeks of weight maintenance with energy intake increased by 460 kJ/day) | Weight loss alone (protocol as in intervention group) | Adiponectin |
C: 33±1.0 |
Values are presented as mean±standard deviation. BMI, body mass index; I, intervention group; C, control group; T2DM, type 2 diabetic mellitus; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; TNF-α, tumor necrosis factor α; IL-6, interleuk in 6; PAI-1, plasminogen-activator inhibitor 1; ACE, angiotensin-converting-enzyme; AR, angiotensin II receptor; HDL, high density lipoprotein. aEPA and DHA were used in two separate treatment arms, bThe patients consumed 1,015.4±231.1 kcal/day, cValues are presented as median (interquartile range).