Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension.

摘要

OBJECTIVES: Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from HDL towards triglyceride-rich lipoproteins. We compared baseline plasma lipids, HDL lipids, plasma LCAT and CETP activity as well as the lowering of plasma FFA and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia in patients with essential hypertension and control subjects. SETTING: University Hospital, Groningen. SUBJECTS AND DESIGN: Eight patients with essential hypertension and eight control subjects were studied during a 3-h hyperglycaemic glucose clamp (blood glucose, 10 mmol L-1). MAIN OUTCOME MEASURES: Plasma insulin, FFA, triglycerides and HDL lipids, plasma LCAT and CETP. RESULTS: Baseline plasma FFA, total cholesterol and HDL cholesterol were not different between the groups, but plasma triglycerides tended to be higher in the hypertensive patients (P < 0.10). The baseline HDL free cholesterol content and the HDL free cholesterol/cholesteryl ester ratio were lower (P < 0.05 for both) in the hypertensive than in the control group. Although baseline plasma LCAT and CETP activity were not significantly different between the groups, the plasma LCAT/CETP ratio, reflecting the amount of active LCAT compared to that of CETP, was higher in the hypertensive patients (P < 0.05). In the combined subjects and in the hypertensive group, the HDL free cholesterol content was negatively related to plasma triglycerides and to the LCAT/CETP ratio, whereas this ratio was positively correlated with plasma triglycerides (P < or = 0.01 for all correlations). During a 3-h hyperglycaemic clamp (blood glucose 10 mmol L-1) plasma FFA and triglycerides decreased to a lesser extent (P < 0.02 and P = 0.05) and remained higher (P < 0.05 for both) in the hypertensive patients, despite similar plasma insulin levels. CONCLUSION: The action of insulin on FFA metabolism is impaired which is likely to contribute to higher plasma triglycerides in essential hypertension. In turn, higher triglycerides influence the HDL lipid composition, either directly or via an effect on the plasma LCAT/CETP ratio.