Effects of n−3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation

Background Effects of fish oil supplements on metabolic variables are insufficiently clarified in type 2 diabetes. Objective We aimed to investigate short-term (1 wk) and longer-term (9 wk) effects of n-3 fatty acids. Design Twenty-six subjects with type 2 diabetes without hypertriacylglycerolemia participated in a double-blind controlled study. Median intake in the intervention group was 17.6 mL fish oil/d (1.8 g 20:5n-3, 3.0 g 22:6n-3, and 5.9 g total n-3 fatty acids). The control group received 17.8 mL corn oil/d (8.5 g 18:2n-6). Results Plasma phospholipid 20:5n-3 and 22:6n-3 increased, whereas 18:2n-6 decreased, in the fish oil group compared with the corn oil group after 1 wk. The two n-3 fatty acids also increased in adipose tissue biopsy samples taken after 9 wk in the fish oil group. Glucose concentrations (home-monitored) were approximately 1 mmol/L higher in the fish oil group than in the corn oil group at the end of the intervention (P = 0.035). Glucose utilization measured by using an isoglycemic clamp was lowered in the fish oil group compared with that in the corn oil group at the end of the intervention (P = 0.049), whereas glucagon-stimulated C-peptide tended to increase (P = 0.078). The fish oil group utilized less fat for oxidation after 1 wk, with a change to more fat and less carbohydrate oxidation after 9 wk (P = 0.040), than did the corn oil group. Conclusion A high intake of fish oil moderately increases blood glucose and decreases insulin sensitivity in persons with type 2 diabetes without hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time-dependent manner.