Platelet Redox Balance in Diabetic Patients With Hypertension Improved by n-3 Fatty Acids

• Published in: Diabetes care Vol. 36; no. 4; pp. 998 - 1005
• Main Authors: MCDONALD, Denise M, O'KANE, Fiona, MCCONVILLE, Maeve, DEVINE, Adrian B, MCVEIGH, Gary E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2013
• Subjects: Aged; Biological and medical sciences; Blood Platelets - metabolism; Cardiovascular diseases; Complications and side effects; Cross-Over Studies; Development and progression; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diet therapy; Diabetes. Impaired glucose tolerance; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Fatty Acids, Omega-3 - therapeutic use; Female; Fish oils; Genetic aspects; Humans; Hypertension - blood; Hypertension - diet therapy; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous; Mortality; Nitric oxide; Original Research; Oxidation-Reduction; Physiological aspects; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk factors; Studies; Superoxides - metabolism; Type 2 diabetes; United Kingdom; Endocrinopathy; Human; Hypertension; Nutrition; Diabetes mellitus; Lipids; Cardiovascular disease; Patient; Metabolic diseases; n-3 fatty acid; Platelet; Unsaturated fatty acid; Balance; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc12-0304

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance. We randomized hypertensive T2DM patients (T2DM HT; n = 22) and age-and-sex matched hypertensive study participants without diabetes (HT alone; n = 23) in a double-blind, crossover fashion to receive 8 weeks of n-3 PUFAs (1.8 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid) or identical olive oil capsules (placebo), with an intervening 8-week washout period. Platelet nitrite and superoxide were measured and compared before and after treatment; 8-isoprostane was determined by ELISA and subcellular compartmentalization of the NAD(P)H oxidase subunit p47-phox examined by Western blotting. The n-3 PUFA supplementation reduced 8-isoprostane and superoxide levels in platelets from T2DM HT, but not HT alone, participants, without effect on nitrite production. This coincided with a significant decrease in p47-phox membrane localization and a similar reduction in superoxide to that achieved with apocynin. At baseline, a subcohort of T2DM HT and HT alone participants showed evidence of nitric oxide synthase (NOS)-derived superoxide production, indicating defective enzymatic activity. This was reversed significantly in T2DM HT participants after treatment, demonstrating improved NOS function. Our finding that n-3 PUFAs diminish platelet superoxide production in T2DM HT patients in vivo suggests a therapeutic role for these agents in reducing the vascular-derived oxidative stress associated with diabetes.