Effects of an acute increase in plasma triglyceride levels on glucose metabolism in man

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2. Opposite results were found for lipid oxidation, which remained unchanged during test 1 as compared with the control period but significantly decreased during tests 2 and 3. Hepatic glucose production was less inhibited during test 1 than during tests 2 and 3, and less so during test 2 than test 3. In conclusion, at least under these particular conditions, acute hypertriglyceridemia induced by Intralipid infusion seems to decrease forearm glucose uptake, glucose oxidation, and insulin-induced suppressibility of hepatic glucose production. Taking our results together, it seems that the triglyceride effect on carbohydrate metabolism occurs via triglyceride hydrolysis using the intracellular pathways of FFA without interference with the circulating FFA pool.