title: Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency.
abstract: 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.
authors.affiliation: Departments of Internal Medicine, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: Twickler
authors.forename: H W
authors.initials: HW
authors.lastname: Wilmink
authors.forename: P C
authors.initials: PC
authors.lastname: Schreuder
authors.forename: M C
authors.initials: MC
authors.lastname: Cabezas
authors.forename: P S
authors.initials: PS
authors.lastname: van Dam
authors.forename: H P
authors.initials: HP
authors.lastname: Koppeschaar
authors.forename: D W
authors.initials: DW
authors.lastname: Erkelens
authors.forename: G M
authors.initials: GM
authors.lastname: Dallinga-Thie
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000097:blood
chemical_list: D008074:Lipoproteins; D014280:Triglycerides; D014801:Vitamin A; D019382:Human Growth Hormone; D013006:Growth Hormone; D002784:Cholesterol