Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects.

The metabolic effects of circadian GH levels in the very low physiological range are unknown. Therefore, we studied 1) GH-deficient patients on receiving GH replacement therapy in whom the last GH injection was replaced with a constant iv infusion starting at 24 h of either GH (35 micrograms/h) or saline (SAL), and 2) an untreated healthy control group. Glucose turnover, indirect calorimetry, and forearm exchange of metabolites were investigated the following day in the basal state (8-11 h) and during a euglycemic (11-13 H) and a hypoglycemic (13-14 h) glucose clamp. During infusion, steady state GH levels increased by 1.9 micrograms/L. Basal and insulin-stimulated energy expenditures (EE) were lower in the patients during SAL than during GH infusion, and the basal respiratory exchange ratio was also lower during GH treatment. Protein EE was elevated during SAL compared to GH infusion (P < 0.05). During the clamp, forearm glucose uptake decreased in the GH study compared to that in the SAL study ((P < 0.05). The patients in the SAL study were more sensitive to insulin during the clamp in terms of suppression of endogenous glucose production (EGP; P < 0.05) and infusion rate of glucose necessary to maintain euglycemia (M value; P < 0.01). Lipid oxidation, in particular in the basal state, was decreased during SAL compared to GH infusion (P < 0.01). The SAL-treated compared with the control group was characterized by decreased basal and insulin-stimulated EE (P < 0.01), increased protein EE (P < 0.01), and hypersensitivity to insulin in terms of suppression of EGP (P < 0.05) and M value (P < 0.01). During the hypoglycemic clamp, the patients in the SAL study were hypersensitive to the hypoglycemic actions of insulin in terms of increased M-value and suppression of EGP, and lipolysis was impaired, as judged by the inhibition of net forearm uptake of FFA. In conclusion, very low GH levels exert powerful actions on day-to-day metabolism, resulting in protein and glucose sparing at the expense of lipids.