Diabetes, Vol 42, Issue 7 1082-1085, Copyright © 1993 by American Diabetes Association
Effect of glucocorticoid and growth hormone treatment on proinsulin levels in humans
SE Kahn, FF Horber, RL Prigeon, MW Haymond and D Porte
Department of Medicine, University of Washington, Seattle.
Treatment with glucocorticoids is associated with a disproportionate
elevation in the PI/IRI ratio. To determine whether growth hormone--another
agent capable of producing insulin resistance and changing B-cell
function--also alters the PI/IRI ratio and whether growth hormone and
glucocorticoids have a synergistic effect on PI and IRI levels, we examined
these variables in four groups of young healthy subjects (n = 8/group)
after 7 days of treatment with placebo, prednisone (0.8 mg.kg-1 x day-1),
rhGH (0.1 mg.kg-1 x day-1), and the combination of prednisone and rhGH.
Fasting plasma glucose levels increased significantly above those of the
control group in subjects receiving prednisone or prednisone and rhGH but
not in subjects receiving rhGH alone. The basal concentration of IRI
increased in response to prednisone, rhGH, and the combination of
prednisone and rhGH. However, this increase in IRI was largely due to an
increase in PI, so that the PI/IRI ratio increased from 14.7 +/- 2.4% in
control subjects to 33.9 +/- 5.3% in subjects on prednisone (P < 0.005),
40.9 +/- 4.3% in individuals receiving rhGH (P < 0.001 vs. control
subjects), and 58.1 +/- 9.2% in subjects receiving both prednisone and rhGH
(P < 0.001 vs. control subjects). We suggest that this change in PI/IRI
with glucocorticoid and growth hormone treatment may be due to an
alteration in B-cell synthesis or release of PI. This change in the PI/IRI
ratio is not dependent on fasting hyperglycemia but may contribute to the
hyperglycemia often observed with these agents. Furthermore, these data
show that IRI is not a reliable indicator of true insulin levels or insulin
sensitivity in either growth hormone- or glucocorticoid-treated subjects.