Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus

Abstract Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n- 3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n- 3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n -3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5 n -3: median, 1.5% [interquartile range, 0.6%] vs −0.2% [0.2%], P = .001; 22:6 n -3: 0.8% [0.4%] vs −0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production ( P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat ( P = .062) compared with Intralipid only, correlating with the rise in individual n -3 NEFA ( r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F 2 -isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n- 3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.