A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: The Sysdimet study

Low-grade inflammation and endothelial dysfunction may play a role in the pathogenesis of type 2 diabetes and cardiovascular disease. We evaluated whether a diet high in fatty fish, bilberries and wholegrain products (Healthy Diet) improves biomarkers reflecting inflammation and endothelial dysfunction in individuals with impaired glucose metabolism. We recruited individuals with impaired glucose metabolism and features of the metabolic syndrome into a 12 week, parallel design, dietary intervention trial conducted at the Department of Clinical Nutrition, University of Eastern Finland (Kuopio, Finland). Randomisation was performed by matching according to sex and medians of age, BMI and fasting plasma glucose of the study population at screening. The primary endpoint in the present study was the change in plasma inflammatory markers and the measurements were performed blinded to group assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin responses were also analysed separately in participants not using statins (n = 76). Altogether, 131 individuals were assigned to either the Healthy Diet (n = 44), a whole-grain-enriched diet (WGED) (n = 42) or a control (n = 45) diet, and 104 participants (mean +/- SD: age 59 +/- 7 years; BMI 31.1 +/- 3.5 kg/m(2)) who had completed the study, were analysed (Healthy Diet n = 36, WGED n = 34 and control diet n = 34). Plasma E-selectin decreased only in the Healthy Diet group. This occurred in all group participants (p < 0.05) and also after excluding participants using statins (p < 0.05). Plasma hsCRP levels decreased in the Healthy Diet (median -17%, p < 0.05) and WGED (median -27%, p < 0.01) groups in participants not using statins. Controlling for confounding factors, including BMI or insulin sensitivity, did not alter the results. A greater increase in plasma concentration of very-long-chain n-3 fatty acids and in the intake of fibre during the study was associated with a greater decrease in plasma E-selectin (p < 0.05). The intake of test breads consumed during the Healthy Diet and WGED interventions was inversely associated with the change in hsCRP levels (p < 0.001). Our results suggest that the combined effect of fatty fish, bilberries and wholegrain products may improve endothelial dysfunction and inflammation in overweight and obese individuals at high risk of developing diabetes. ClinicalTrials.gov NCT00573781 The study was funded by the Academy of Finland (117844 and 118590 [to M. Uusitupa]; 131460 [to K. Poutanen]; 130469 [to H. Mykkanen] and 131593 [to V. D. F. de Mello]); the Kuopio University Hospital (5106, 5168, 5254 [to M. Uusitupa]); the Finnish Diabetes Research Foundation; the Sigrid Juselius Foundation; the Nordic Centre of Excellence on 'Systems biology in controlled dietary interventions and cohort studies' (SYSDIET; 070014); and the European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD-CT-2005-514008).