Intravenous intralipid-induced blood pressure elevation and endothelial dysfunction in obese African-Americans with type 2 diabetes

Abstract

Objective: Increased free fatty acids (FFAs) are leading candidates in the pathogenesis of insulin resistance and hypertension in obese subjects. We evaluated the effect of sustained elevations of FFA on blood pressure, endothelial function, insulin secretion, inflammatory markers, and renin-angiotensin system.

Research design and methods: Twenty-four obese, African-American, normotensive diabetic subjects received a sequential 48-h infusion of Intralipid (20%, 40 ml/h) plus heparin (250 units/h) or normal saline (40 ml/h) plus heparin (250 units/h).

Results: Blood pressure was significantly increased within 4 h of lipid infusion and reached a peak increment of 13 mm Hg in systolic and 5 mm Hg in diastolic blood pressure at 24 h (P < 0.01). Compared to baseline, lipid infusion reduced flow-mediated dilatation by 11% at 24 h and 18% at 48 h (P < 0.001). FFA and triglyceride levels increased from a baseline of 0.5 +/- 0.2 mmol/liter and 135 +/- 76 mg/dl to 1.8 +/- 1.0 mmol/liter and 376 +/- 314 mg/dl at 48 h, respectively (P < 0.01). C-Reactive protein increased by 35% at 24 h and by 110% at 48 h of lipid infusion. There were no significant changes in plasma renin and aldosterone levels during lipid or saline infusions.

Conclusion: Increased FFA levels result in a rapid and sustained elevation in blood pressure, impaired endothelial function, and increased inflammatory markers in obese subjects with type 2 diabetes. The model of FFA-induced hypertension may be useful in examining disease mechanisms associated with the development of hypertension in obese subjects.

Figure 1

Changes in systolic blood pressure (top) and diastolic blood pressure (bottom) during 48-h Intralipid/heparin (closed circles) and saline/heparin (open circles) infusion in obese subjects with type 2 diabetes. Values are mean ± sem. *, P < 0.01. †, P < 0.05.

Figure 2

Changes in plasma FFA (A), aldosterone (B), and renin (C) concentration during 48-h Intralipid/heparin and saline/heparin infusion in obese subjects with type 2 diabetes. Values are mean ± sem. *, P < 0.01.

Figure 3

Changes in FMD during 48-h saline/heparin infusion (open bars) and Intralipid/heparin (closed bars) in obese subjects with type 2 diabetes. Values are mean ± sem. *, P < 0.01.

Figure 4

Changes in glucose, C-peptide, and C-peptide/glucose ratio during 48-h Intralipid/heparin and saline/heparin infusion in obese subjects with type 2 diabetes. Values are mean ± sem.