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

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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.

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