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Growth Hormone (GH) Treatment Decreases Postprandial Remnant-Like Particle Cholesterol Concentration and Improves Endothelial Function in Adult-Onset GH Deficiency¹

Departments of Internal Medicine G02.228 (T.B.T., H.W.W., P.C.N.J.S., M.C.C., D.W.E., G.M.D.-T.) and Endocrinology (P.S.v.D., H.P.F.K.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands

Address correspondence and requests for reprints to: Dr. G. M. Dallinga-Thie, Department of Vascular Medicine, G02.228, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: Gdalling{at}azu.nl

Premature atherosclerosis is a clinical feature in adult-onset GH deficiency. Evidence is accumulating that disturbances in triglyceride metabolism, reflected by abnormalities in circulating remnant lipoproteins, are associated with increased atherogenic potential. In a case-controlled intervention study, we investigated postprandial lipoprotein metabolism using a new remnant lipoprotein method based on immunoseparation principle [RLP-cholesterol (RLP-C)]. In addition, we analyzed retinyl ester (RE) analysis in plasma and in Sf < 1000 fraction. Endothelial function was assessed as flow-mediated dilatation (FMD). Eight patients diagnosed with acquired adult-onset GH deficiency and eight controls matched for gender, age, body mass index, and apolipoprotein (apo) E genotype were enrolled in the study. Oral vitamin A fat loading tests were performed at baseline in both groups and after 6 months of treatment with recombinant human GH (rh-GH) in the adult-onset GH-deficient patients. Adult-onset GH-deficient patients had significantly higher fasting RLP-C, postprandial RLP-C concentrations (plasma RLP-C, 0.29 ± 0.14 mmol/L; and incremental area under the curve-RLP-C, 2.13 ± 1.60 mmol*h/L, respectively) than controls (0.19 ± 0.06 mmol/L and 1.05 ± 0.72 mmol*h/L (P < 0.05), respectively). They also had significantly higher postprandial RE in plasma and Sf < 1000 fraction. Treatment with rh-GH significantly reduced postprandial RLP-C concentrations (incremental area under the curve-RPL-C 0.73 ± 0.34 mmol*h/L; P < 0.05) but had no effects on the fasting RLP-C concentrations (0.317 ± 0.09 mmol/L, P < 0.05), or on the postprandial RE in plasma and in Sf < 1000 fraction. Endothelial function measured as FMD was improved from 5.9 ± 3.3% to 10.2 ± 4.0% (P < 0.05) in patients treated with rh-GH.

It is concluded that patients with adult-onset GH deficiency have increased levels of fasting and postprandial RLP-C and an impaired endothelial function as measured as FMD. Treatment with rh-GH resulted in a decrease of postprandial RLP-C concentration, thereby improving the postprandial atherogenic lipoprotein profile and improvement of endothelial function, however, the clearance of large chylomicron particles as reflected by RE remained disturbed.

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