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Abstract. We studied the metabolic clearance rate (MCR) serum half-time (t_½) and apparent distribution space (DS) of unlabelled, authentic, biosynthetic human growth hormone (B-hGH) in 9 GH-deficient patients by means of the constant iv infusion to equilibrium technique. B-hGH was infused for 3 h at a rate of 33 ng · kg⁻¹ · min⁻¹ after which the disappearance from serum of GH was followed for 1 h. The mean ± sem values for MCR, t_½ and DS were: 2.3 ± 0.6 ml · kg⁻¹ · min⁻¹, 21.1 ± 1.7 min and 67.6 ± 14.6 ml/kg, respectively. The disappearance of GH was monoexponential for the first 30 min, during which 75% of the GH had been cleared. The disappearance rate during the last 30 min of the observation period was somewhat lower, still approximately 90% of the GH had been eliminated after 60 min.

Abstract. The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng· kg⁻¹·min⁻¹) in the same 9 GH deficient patients. A 3-h lag period was interposed between the iv and the sc infusion. Iv infusion was continued for 3 h. All 9 subjects subsequently received sc infusion for 19 h and five of them continued for additionally 24 h. The mean steady state serum GH level in the nine patients was 23.1 ± 5.1 μg/l after iv and 6.8 ± μg/l after sc administration (P < 0.01). Extension of the sc infusion period in 4 of the subjects did not significantly alter the serum GH level (P > 0.15), implying that a steady state was reached. The GH in the infusion system was stable throughout a 24-h period. We therefore conclude that sc injected GH is degraded locally to a substantial extent.

Abstract.

There is evidence that hyperketonemia in insulin-dependent diabetes may be aggravated by a decreased disposal rate for ketone bodies. To test the hypothesis that this decrease may be induced by concomitant hyperglycemia through substrate competition at the acetyl-CoA level, 5 young insulin-dependent diabetic subjects received at 2-h iv infusion of 0.9 mmol 3-hydroxybutyrate · kg⁻¹ · h⁻¹ at clamped 1. euglycemia (5 mmol/l) and 2. hyperglycemia (11 mmol/l) on separate occasions. To ensure similar metabolic conditions, a low-dose hyperinsulinemic euglycemic clamp was performed during the 5 h preceding the actual studies. Substrate fluxes in muscle were assessed through the forearm technique. The glucose infusion rate was 4.9 and 2.9 mg· kg⁻¹·min⁻¹, and the forearm arteriovenous difference for glucose was 0.72 during hyperglycemia and 0.39 mmol/l (p<0.05). during euglycemia. Hyperglycemia did not affect circulating levels of free insulin, glucagon, nonesterified fatty acids, 3-hydroxybutyrate (hyperglycemia: 665, euglycemia: 770 μmol/l, p>0.05) or acetoacetate, nor forearm uptake of 3-hydroxybutyrat (hyperglycemia, 152, euglycemia: 168 μmol/l, p>0.05). In conclusion, our results do not suggest any inhibitory role for hyperglycemia in the disposal of ketone bodies. In as much as extrapolation from the present well insulinized state is appropriate, the data indicate that alternative mechanisms may be involved in the observed impairment of ketone body clearance in hyperketonemic insulin-dependent diabetic patients.

Abstract. In a double-blind cross-over study we compared pituitary and methionine-free biosynthetic human growth hormone (P-hGH and B-hGH) with respect to pharmacokinetics and short-term metabolic effects in 9 hypopituitary children. They treated themselves for 4 weeks with 2 IU sc daily at 20.00 h. After admittance to hospital 2 IU was given: im the first day, and sc the second. They then switched over to the alternative preparation. The serum profiles of B- and P-hGH were identical. Comparing im and sc adsorption, the latter was slower and resulted in smaller areas under the curves, indicating greater local degradation.

Both preparations caused identical increases in somatomedin-C, but slightly more sustained after sc injection. Plasma glucose, plasma glucagon, and serum insulin fluctuated within normal ranges. The glucose profile pointed at a modest anti-insulin effect of hGH when given in the morning. The concentration in the blood of lactate, alanine, glycerol and B-OH-butyrate, and in serum of triglyceride, cholesterol and carbamide revealed no abnormalities with either hGH preparation. Finally, no development of anti-GH or E. coli polypeptide antibodies was seen. In conclusion, the pharmacokinetics and short-term metabolic effects of B-hGH and P-hGH were identical.