LONG-TERM EFFECTS OF FISH-OIL ON INSULIN-RESISTANCE AND PLASMA-LIPOPROTEINS IN NIDDM PATIENTS WITH HYPERTRIGLYCERIDEMIA

OBJECTIVE - The aim of this study was to evaluate the long-term (6-mon th) effects of moderate fish oil supplementation on insulin sensitivit y 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 hypo glycemic drugs remained unchanged throughout the whole experiment. At baseline and after 6 months, insulin sensitivity was measured by eugly cemic hyperinsulinemic clamp (insulin infused, 2.0 mIU . kg(-1) body w t . min(-1)). At the same time, blood glucose control, fasting and pos tprandial serum insulin and nonesterified fatty acid (NEFA) concentrat ions, and fasting plasma lipoprotein concentrations were evaluated. RE SULTS - In the group treated with fish oil compared with the baseline, there was: 1) a significant reduction in both plasma TG (2.92 +/- 0.2 3 vs. 3.85 +/- 0.32 [mean +/- SE] mmol/l, P < 0.01) and VLDL-TG (2.35 +/- 0.24 vs. 4.25 +/- 0.66 mmol/l, P < 0.01), without significant chan ges in blood glucose control; 2) a significant reduction in fasting NE EA concentrations (572 +/- 100 vs. 825 +/- 131 mu mol/l, P < 0.01); an d 3) a significant enrichment in long-chain omega-3 fatty acids of ery throcyte membrane phospholipids. In the placebo group, there were no c hanges 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 NIDD M patients with hypertriglyceridemia, moderate amounts of fish oil ind uce a long-term significant reduction in plasma triglycerides, VLDL tr iglycerides, and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain omega-3 fatty acids, without deteri orating blood glucose control. However, this amount of omega-3 fatty a cids was unable to improve insulin sensitivity in this group of patien ts.