Title: Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men Authors
Submitted to: Metabolic Syndrome and Disorders
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 15, 2011
Publication Date: February 1, 2012
Citation: Kelley, D.S., Adkins, Y.C., Woodhouse, L.R., Swislocki, A., Mackey, B.E., Siegel, D. 2012. Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men. Metabolic Syndrome and Disorders. 10(1):32-38. Interpretive Summary: Insulin resistance (IR) is a reduced ability of insulin to exert its metabolic effects on its target tissues (muscle, liver, and adipose). It is associated with increased plasma concentrations of several lipids, glucose, and insulin. It increases the risks for metabolic syndrome, diabetes, and cardiovascular disease. In 2005 over 40% of people aged 20 and over in the U.S.A. had IR and the prevalence has increased since then. Diets high in saturated, trans-, and omega-6 fatty acids, and low in omega-3 fatty acids are one of the major factors that contribute to the development of IR. We studied the effects of DHA (one of the omega-3 fatty acids in fish oils) supplementation on the circulating concentration of glucose, insulin, and lipid markers of IR. Men with elevated triglycerides (17/group) supplemented their diets with either DHA oil (DHA 3 g/d) or olive oil for 90 days; 12-h fasting, and postprandial (2, 4, 6, 8 h after a test meal) blood samples were drawn before and at the end of DHA supplementation. DHA significantly decreased circulating concentrations of several lipid markers (free fatty acids, triglyceride to HDL-C ratio, small dense LDL particles) of IR, but did not alter concentration of circulating insulin and other markers based on insulin. Our results show that markers of IR based on plasma lipids are more sensitive to DHA supplementation than those based on plasma glucose and insulin concentrations. These findings demonstrate that DHA can reverse dyslipidemia which may further lead to hyperglycemia and diabetes.
Technical Abstract: Background: Obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR. Methods: By using a placebo controlled, parallel study design, we examined the effects of DHA supplementation (3 g/d, 90 d) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group). Results: DHA supplementation increased fasting plasma glucose concentration by 4.9%, (p<0.05) but did not alter other indices of IR based on fasting (insulin and HOMA-IR) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). It decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of non-esterified fatty acids (13.0%), small dense LDL particles (21.7%), and TG:HDL-C ratio (34.0%) (p<0.05 for each variable). None of the variables changed in the placebo group. Conclusions: Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than glucocentric markers. Future studies with DHA in pre-diabetic subjects and direct measures of insulin sensitivity are needed.