Abstract
OBJECTIVE: Offspring of patients with type 2 diabetes (OPDs) exhibits endothelial dysfunction (ED) associated with a chronic inflammatory state. N-3 polyunsaturated fatty acids (n-3 PUFA) may have antioxidant and anti-inflammatory properties that are beneficial for cardiovascular and metabolic health. Therefore, in the present study, we tested the hypothesis that dietary supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise healthy OPDs. METHODS AND DESIGN: A double-blind, placebo-controlled trial was conducted with 50 OPDs. Participants were randomized to treatment with either placebo or n-3 PUFA (2g/day) for 12 weeks. Before and after treatment we evaluated endothelial function (using flow-mediated dilation (FMD) of the brachial artery), circulating inflammatory markers (adiponectin, TNF-alpha, and high sensitivity-CRP), and insulin resistance (QUICKI). RESULTS: No significant changes were observed in study outcomes in subjects treated with placebo. By contrast, when compared with baseline values, subjects treated with n-3 PUFA had significant improvement in FMD (9.1+/-5.8% vs. 11.7+/-4.4%, p=0.02) that was accompanied by decreased plasma triglycerides (117+/-73mg/dl vs. 86+/-44mg/dl, p=0.001) and TNF-alpha levels (8.9+/-2.3pg/ml vs. 6.8+/-2.7pg/ml, p=0.001), and a trend towards increased plasma adiponectin levels (7.8+/-4.5microg/ml vs. 9.5+/-5.1microg/ml, p=0.09). When data were analyzed by multiple regression analysis, decreased TNF-alpha after treatment with n-3 PUFA predicted increased FMD. CONCLUSION: Dietary supplementation with n-3 PUFA significantly improved endothelial function and reduced pro-inflammatory markers in OPDs. Thus, fish oil consumption may have beneficial cardiovascular and metabolic health effects in otherwise healthy subjects predisposed to diabetes and its vascular complications.