BackgroundDespite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis.PurposeTo investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy.MethodsWe conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study.ResultsMajority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group.ConclusionsIn conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests.The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0523-9) contains supplementary material, which is available to authorized users.

BackgroundGrowing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.PurposeWe sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).MethodsWe conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 20) or placebo (n = 28).ResultsAs compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4 % (P < 0.0001), reduction of leptin by 22 % (P < 0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5 % (P < 0.0001) at 30 days, but not at 3–5 days. Compared with placebo adiponectin was 12.7 % higher (P = 0.0042), leptin was 16.7 % lower (P < 0.0001) and A/L ratio was 33.3 % higher (P < 0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P = 0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P < 0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P < 0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P < 0.0001) were: assigned treatment, current smoking and hyperlipidemia.ConclusionsIn high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.Electronic supplementary materialThe online version of this article (doi:10.1007/s10557-013-6457-x) contains supplementary material, which is available to authorized users.