title: 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 (20:5n-3: median, 1.5% [interquartile range, 0.6%] vs -0.2% [0.2%], P = .001; 22:6n-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.
authors.affiliation: Division of Clinical Nutrition, Department of Clinical Service, St. Olavs Hospital, N-7006 Trondheim, Norway. ingrid.mostad@stolav.no
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Mostad
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Bjerve
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.forename: Pauline
authors.initials: P
authors.lastname: Sutton
authors.forename: Keith N
authors.initials: KN
authors.lastname: Frayn
authors.forename: Valdemar
authors.initials: V
authors.lastname: Grill
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001823:Body Composition / Q000187:drug effects; D002096:C-Peptide; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet; D015237:Dinoprost / Q000378:metabolism; D004311:Double-Blind Method; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D007328:Insulin; D028421:Isoprostanes; D005934:Glucagon; D015237:Dinoprost