The effects of replacement with biosynthetic human GH on carbohydrate tolerance and lipid metabolism were studied in 40 hypopituitary adults during a randomized double blind, placebo-controlled trial for 6 months, followed by a 12-month open trial. The daily GH dose was 0.04 +/- 0.01 IU/kg. Fasting plasma glucose, serum fructosamine, plasmid lipids, lipoproteins, and plasma C-peptide concentrations were measured, and an oral glucose tolerance test was performed every 6 months. There was no change in fasting triglyceride levels at any stage of the study. There was no significant change in fasting total or LDL cholesterol, total HDL cholesterol, high density lipoprotein2 (HDL2) cholesterol, HDL3 cholesterol, apoprotein-A1, or apoprotein-B during GH or placebo treatment in the placebo-controlled 6-months study. In the open phase of the trial, total and low density lipoprotein cholesterol showed a sustained downward trend during GH therapy. Compared to the pretreatment level, the HDL cholesterol concentration was significantly higher at 18 months. Cholesterol subfractions HDL2 and HDL3 and apoprotein-A1 and -B were not different from the pretreatment levels. The total/HDL cholesterol ratio decreased significantly at 12 and 18 months. During the controlled phase, fasting plasma glucose was similar during GH and placebo administration, but fasting insulin and C-peptide increased during GH therapy, but not during placebo treatment. The mean area under the curve (AUC) for glucose increased by a small, but significant, extent over the 6 months of GH treatment and was higher at 6 months than during placebo treatment. The AUC for insulin also increased during GH treatment. During the open trial, the fasting plasma glucose level increased at 6 and 12 months, and the fasting plasma insulin level increased at 6, 12, and 18 months of GH treatment. The plasma glucose AUC during the oral glucose tolerance test was significantly higher at 6 months, and the plasma insulin AUC was significantly higher at 6, 12, and 18 months of GH therapy. In conclusion, GH therapy has some metabolic effects that are considered beneficial and others that are less desirable.
