Chronic Low-Dose Lipid Infusion in Healthy Patients Induces Markers of Endothelial Activation Independent of Its Metabolic Effects

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Elevated plasma triglyceride/free fatty acid (FFA) levels and insulin resistance may promote atherosclerosis through endothelial activation (ie, increased expression of intercellular adhesion molecule 1 [ICAM-1]/vascular adhesion molecule 1 [VCAM-1], and endothelin-1 [ET-1]) in patients with the metabolic syndrome, but this has never been directly tested. The authors measured endothelial activation and insulin sensitivity (euglycemic insulin clamp with [3-3H]-glucose) after a 4-day low-dose lipid infusion that elevated plasma FFA to levels observed in the metabolic syndrome in 20 lean, non-diabetic insulin-resistant subjects with a strong family history of type 2 diabetes mellitus (FH+) and 10 insulin-sensitive volunteers without a family history of type 2 diabetes mellitus (FH−). Low-dose lipid infusion reduced insulin sensitivity by approximately 25% in insulin-sensitive FH− controls but did not worsen preexisting insulin resistance in FH+. Low-dose lipid infusion elevated plasma ICAM and VCAM levels similarly in both groups (approximately 12%–18%;P<.01 vs baseline), while plasma ET-1 levels increased more in FH+ vs FH− (46% vs 10%;P=.005). Increased plasma FFA levels closely correlated with elevated ICAM (r=0.60;P<.01), VCAM, and ET-1 levels (r=0.39 andr=0.42, respectively;P<.05). Low-dose lipid infusion induces endothelial activation in both lean insulin-resistant (FH+) and insulin-sensitive (FH−) healthy patients, regardless of changes in insulin sensitivity. These results prove that even a modest lipid oversupply may be sufficient to trigger a deleterious endothelial response.J CardioMetabol Syndr.2008;3:141–146. ©2008 Le Jacq

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