Long-Term Effects of Fish Oil on Insulin Resistance and Plasma Lipoproteins in NIDDM Patients With Hypertriglyceridemia

Abstract

OBJECTIVE The aim of this study was to evaluate the long-term (6-month) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS The study has been performed according to a randomized double-blind placebo-controlled design with a parallel group sequence. After a washout period of 4 weeks and a run-in period of 3 weeks, 16 NIDDM patients with hypertriglyceridemia (triglyceride [TG], 2.25–5.65 mmol/l) were randomly assigned to either fish oil (2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months, then 1.7 g/day for 4 more months) (n = 8) or placebo (n = 8). Diet and hypoglycemic drugs remained unchanged throughout the whole experiment. At baseline and after 6 months, insulin sensitivity was measured by euglycemic hyperinsulinemic clamp (insulin infused, 2.0 mIU · kg−1 body wt · min−1). At the same time, blood glucose control, fasting and postprandial serum insulin and nonesterified fatty acid (NEFA) concentrations, and fasting plasma lipoprotein concentrations were evaluated. RESULTS In the group treated with ffish oil compared with the baseline, there was: 1) a significant reduction in both plasma TG (2.92 ± 0.23 vs. 3.85 ± 0.32 [mean ± SE] mmol/l, P < 0.001) and VLDL-TG (2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l, P < 0.01), without significant changes in blood glucose control; 2) a significant reduction in fasting NEFA concentrations (572 ± 100 vs. 825 ± 131 μmol/l, P < 0.01); and 3) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids. In the placebo group, there were no changes in any of the variables analyzed. The insulin-mediated glucose uptake was unchanged in both groups (fish oil, 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months; placebo, 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months). CONCLUSIONS In NIDDM patients with hypertriglyceridemia, moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides, VLDL triglycerides, and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids, without deteriorating blood glucose control. However, this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients.