Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency:A stable isotope study

Patients with adult GH deficiency are often dyslipidemic and may have an in creased risk of cardiovascular disease. The secretion and clearance of very low density Lipoprotein apolipoprotein B 100 (VLDL apoB) are important det erminants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turn over technique. VLDL apoB kinetics were determined in 14 adult patients wit h GH deficiency before and after 3 months GH or placebo treatment in a rand omized double blind, placebo-controlled study using a primed constant [1-C- 13]leucine infusion. VLDL apoB enrichment was determined by gas chromatogra phy-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insul in concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A(1C) 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 k g (P < 0.01). The total cholesterol concentration (P < 0.02), the low densi ty lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholester ol/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 ob served in the placebo group. This study suggests that GH replacement therap y improves lipid profile by increasing the removal of VLDL apoB. Although G H 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 composit ion.