Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht 3508 AB, The Netherlands
Address all correspondence to: T. B. Twickler, M.D., Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, KC02.069.1, PO Box 85090, 3508 AB, Utrecht, The Netherlands. E-mail: . th.b.twickler{at}digd.azu.nl
To the editor:
Kearney et al. (1) recently published an interesting study in which they investigated the composition of very low-density lipoprotein (VLDL) in combination with apolipoprotein (apo) B100 kinetics to elucidate the proatherogenic lipid profile in hypopituitarism. They report an increase in the plasma triglyceride (TG) levels, which could be explained by an increase in TG in the VLDL apo B100 fraction in the patients with hypopituitarism compared with matched control subjects. In addition, the increased amount of VLDL apo B100 in the plasma compartment is due to an increased VLDL apo B100 production rate, although statistical significance was not reached. Finally, The authors draw the conclusion that the proatherogenic lipoprotein profile in hypopituitarism [that is mostly characterized by elevated plasma levels of LDL-cholesterol and TG rich particles (TRP)] is caused by a TG increase in the VLDL apo B100 fraction and by the total number of VLDL apo B100 particles, a lipoprotein profile that is almost similar to what is observed in type II diabetic patients (2).
We would like to make some additional comments to further explain the disturbances in TRP metabolism that may originate in the proatherogenic lipoprotein profile in hypopituitarism. Small dense LDL is strongly atherogenic. The origin of small dense LDL is likely the product of the intravascular lipoprotein remodelling through neutral lipid exchange, facilitated by the increase of large TG-rich VLDL particles (so-called VLDL1). Malmstrom et al. (3) recently showed that acute hyperinsulinemia in normal individuals lowered plasma TG and VLDL levels principally by suppressing VLDL-1 apo B100 production rate, without an effect on VLDL-2 apo B100 production. These results indicate that the rates of VLDL-1 and VLDL-2 apo B100 production in the liver are independently regulated. In most of the hypopituitary patients (11 of 16), the body mass index was at least 26 kg/m2, and as a consequence a decrease in insulin sensitivity can be expected in this subgroup of patients. Estimation of the insulin sensitivity by plasma insulin levels or the homeostatic model assessment index was unfortunately not shown. In a state of decreased insulin sensitivity, as expected in hypopituitary patients, a defective down-regulation of VLDL-1 by insulin may result in a rise of precursors for small dense LDL (4). Therefore, the explanation of the origin of the proatherogenic lipid profile in hypopituitarism necessitates an additional separation of the VLDL apo-B100 fraction.
In conjunction with our own recent observations (5), we do support the conclusion that premature atherosclerosis in hypopituitarism is probably due to an atherogenic lipoprotein profile. However, additional research is needed to explore the basic disturbances in TRP metabolism that may be responsible for the proatherogenic lipoprotein profile in adult GH deficiency.
Received December 11, 2001.
References
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