Growth Hormone and Glucose Metabolism

In adult patients with GH deficiency, it is well documented that treatment with recombinant human GH results in a reduction of visceral fat mass and an increase in muscle mass. During long-term treatment, these effects seem to have beneficial effects on glucose metabolism. However, during the initial phase of GH treatment the insulin antagonistic effect of GH often induces an insulin resistant state which leads to an increase in insulin secretion or even, in cases with a preexisting ß-cell defect, to overt diabetes. Due to the lipolytic effect of GH, an impact of GH treatment on intracellular lipid homeostasis in adipose tissue, but also in skeletal muscle cells and liver cells can be expected. Moreover, since insulin resistance is known to be closely correlated with intramyocellular lipid (IMCL) content, changes in IMCL can play a key role in the GH-induced changes in the insulin sensitivity. Anyway, the mechanisms involved in the pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin resistance under long term treatment are presently not fully understood. In order to verify these mechanisms, we intend to establish changes in IMCL in patients with GH deficiency by MR-spectroscopy before and during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and insulin clearance. Finally, we aim to justify the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.

Inclusion criteria

• Patients >18 years old.
• Severe GH deficiency as diagnosed by an inadequate GH stimulation in three different tests:

• peak response < 3 µg/l during an insulin tolerance test;
• < 3 µg/l during glucagon test;
• < 9 µg/l during GHRH-arginine stimulation test).

Exclusion criteria

• GH replacement therapy prior to inclusion.
• History of diabetes Type 1 or 2.
• Biochemical evidence of impaired hepatic or renal function.
• History of cardiovascular disease.
• Uncontrolled hypertension.
• Current inflammatory or malignant disease.
• Pregnancy.