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Effects of Growth Hormone (GH) Replacement Therapy on Very Low Density Lipoprotein Apolipoprotein B100 Kinetics in Patients with Adult GH Deficiency: A Stable Isotope Study1
Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of...
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Published in: | The journal of clinical endocrinology and metabolism 1999-01, Vol.84 (1), p.307-316 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Patients with adult GH deficiency are often dyslipidemic and may have
an increased risk of cardiovascular disease. The secretion and
clearance of very low density lipoprotein apolipoprotein B 100 (VLDL
apoB) are important determinants of plasma lipid concentrations. This
study examined the effect of GH replacement therapy on VLDL apoB
metabolism using a stable isotope turnover technique. VLDL apoB
kinetics were determined in 14 adult patients with GH deficiency before
and after 3 months GH or placebo treatment in a randomized double
blind, placebo-controlled study using a primed constant[
1-13C]leucine infusion. VLDL apoB enrichment was
determined by gas chromatography-mass spectrometry. GH replacement
therapy increased plasma insulin-like growth factor I concentrations
2.9 ± 0.5-fold (P < 0.001), fasting insulin
concentrations 1.8 ± 0.6-fold (P < 0.04),
and hemoglobin A1C from 5.0 ± 0.2% to 5.3 ±
0.2% (mean ± sem; P < 0.001).
It decreased fat mass by 3.4 ± 1.3 kg (P <
0.05) and increased lean body mass by 3.5 ± 0.8 kg
(P < 0.01). The total cholesterol concentration
(P < 0.02), the low density lipoprotein
cholesterol concentration (P < 0.02), and the VLDL
cholesterol/VLDL apoB ratio (P < 0.005) decreased.
GH therapy did not significantly change the VLDL apoB pool size, but
increased the VLDL apoB secretion rate from 9.2 ± 2.0 to
25.9 ± 10.3 mg/kg·day (P < 0.01) and the
MCR from 11.5 ± 2.7 to 20.3 ± 3.2 mL/min
(P < 0.03). No significant changes were observed
in the placebo group. This study suggests that GH replacement therapy
improves lipid profile by increasing the removal of VLDL apoB. Although
GH therapy stimulates VLDL apoB secretion, this is offset by the
increase in the VLDL apoB clearance rate, which we postulate is due to
its effects in up-regulating low density lipoprotein receptors and
modifying VLDL composition. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.84.1.5365 |