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The comparative potency of equimolar amounts of soluble porcine and semisynthetic human insulin were studied in ten patients with type 1 diabetes in acute experimental situations. In both situations residual subcutaneous insulin depots were eliminated by intramuscular treatment exclusively with soluble insulin four days before the experiments. Then, practically identical metabolic states were achieved by connecting the patients to a glucose-controlled insulin infusion system (Biostator) 12 hours before the study. In one study, 0.5 g/kg body weight of glucose was administered intravenously as a bolus, and thereafter insulin was infused at a rate of 1.0 mU/kg/min. The decline in blood glucose was rectilinear and identical for the two insulins: y = -1.18x + 206 and y = -1.17x + 205. The insulin effect is well below maximum, and a 10% increase in the infusion rate of insulin was easily detected. Although changes in blood glucose and pancreatic glucagon were identical, a significantly lower plasma growth hormone level was noted after human insulin infusion. In the second study, 24 hours of near-normoglycemia was attained by the glucose-controlled insulin infusion system, the patients being supine and having identical meals at identical intervals. The diurnal blood glucose, plasma growth hormone, and pancreatic glucagon patterns were identical and the total 24 hour insulin consumption was 47.7 +/- 3.5 units and 47.7 +/- 3.7 units for the two insulins.

Five diabetic and 14 non-diabetic uraemic patients on long-term haemodialysis were studied during twenty-one 24 h periods including 5 to 7 h of haemodialysis against glucose-free acetate buffered dialysis fluid. Half-hourly blood samples were collected for hormonal and metabolite analysis. In addition, blood samples were analyzed in 40 experiments covering the haemodialysis and a pre-dialysis period. Before dialysis, plasma growth hormone levels were high and fluctuating, but almost always fell to low normal values within the first 2 h of haemodialysis. In the diabetic uraemic patients, the occasional severe hypoglycaemic episodes occurring during haemodialysis did not provoke growth hormone release, and hypoglycaemic reactions were not encountered. Intravenous acetate infusion studies resulted in plasma concentrations ranging from 1.3. to 2.7 mmol, ie. about 60 per cent of the levels reached during haemodialysis and in suppression of growth hormone secretion. It is suggested that the fall in growth hormone levels and the lack of hypoglycaemic symptoms during haemodialysis is due to the use of acetate as a fuel in brain.

In normal subjects during 24-hours saline infusion, plasma prolactin showed a number of small rises during day and night. The mean night-time level was significantly higher than the day-time level (8.2 +/- 0.6 ng/ml as against 4.7 +/- 0.5 ng/ml). In 12 insulin-dependent diabetics the 24 h plasma prolactin pattern was identical to that found in normals. Somatostatin infusion (4 mg/24 h in normals; 2--6 mg/24 h in diabetics) had no effect on the 24 h plasma prolactin pattern in either normals or in diabetics.

Juvenile diabetic patients were studied 60-72 hours after insulin withdrawal when moderate ketoacidosis had developed. Somatostatin infusion for 4 hours in five patients resulted in almost complete suppression of plasma pancreatic glucagon and growth hormone, a fall in plasma-cyclic-adenosine-monophosphate (A.M.P.) concentrations, and a large fall in plasma-glucose concentration. After infusion plasma concentrations of these substances rose again. Blood-ketone-bodies, plasma-free-fatty-acids (F.F.A.), and plasma glycerol concentrations, however, did not decrease appreciably with somatostatin administration. In three patients 2 to 3 h somatostatin infusions were twice superimposed upon a continuous 9-5 h insulin infusion (1 unit/h). An insulin effect was noticeable within 30 minutes, with pronounced falls in the concentrations of plasma glucose, pancreatic glucagon, F.F.A., and blood-ketone-bodies. There was no significant change in these patterns when somatostatin was administered or withdrawn. These results do not indicate that somatostatin infusion would be useful in the treatment of manifest diabetic ketoacidosis.

Somatostatin was infused in various doses into normal subjects and juvenile diabetics for a 24-hour period preceded by a 24-hour control period and followed by another three-hour control period. Saline was infused during the first control period. Meals were served during the two 24-hour periods. Blood samples were taken hourly. Five normal males received a total dose of 4 mg. somatostatin. Four male diabetics received 2 mg., four received 4 mg., and four 6 mg. In the diabetics, somatostatin suppressed plasma growth hormone, glucagon, and glucose throughout the infusion. All parameters rebounded at cessation of infusion. In the normals, somatostatin suppressed plasma growth hormone, glucagon, and insulin but increased plasma glucose. It is concluded that the plasma glucose suppression in the diabetics is mainly due to the suppression of the diabetogenic hormones growth hormone and glucagon. A minor effect of decreased and/or delayed absorption of carbohydrates cannot be excluded in these experiments. The elevated plasma glucose levels in normals must be due to the suppressive effects of somatostatin on insulin secretion.

The serum-growth hormone response to exercise is greater and occurs earlier in juvenile diabetics than in nondiabetics. A simple exercise test has been devised which unequivocally reveals the growth hormone hypersecretion of juvenile diabetics. Using this procedure we have shown that after a period of exceedingly strict metabolic control of the diabetes, complete normalization of growth hormone secretion is attained. It is concluded that the abnormalities in serum growth hormone found in juvenile diabetics are of a metabolic origin.

Studies in five male patients with recently diagnosed juvenile diabetes showed a raised mean level of serum growth hormone, which fluctuated considerably over a 24-hour period. It is suggested that the secretion rate of growth hormone is raised in this condition.

Groups of male nonobese juvenile diabetics with recent onset, short term (1-8 yr), and long-term (12-30 yr) diabetes as well as comparable nondiabetic controls were studied during exercise experiments. The chosen exercise load, 450 kg/min for 20 min never induced changes in serum growth hormone in our nondiabetic control subjects. THE PRINCIPAL RESULTS OF THE STUDY WERE AS FOLLOWS: (a) an immediate high rise in serum growth hormone followed the commencement of exercise in all diabetics. The increase and pattern of serum growth hormone was not related to the duration of the diabetes. (b) The abnormal growth hormone response to exercise in diabetics was observed when the patients were in poor control as well as when they were in clinically excellent control (fasting blood glucose level between 100 and 140 mg/100 ml). (c) However, the abnormal serum growth hormone response was significantly diminished when exceedingly strict control was achieved (fasting blood glucose level between 60 and 100 mg/100 ml). In two of these experiments an entirely normal growth hormone pattern was obtained. (d) The change in serum growth hormone pattern during regulation was totally unrelated to the changes in serum free fatty acid patterns. A normal free fatty acid level and exercise pattern was obtained much earlier during the improved control. (e) Fasting serum growth hormone levels were also significantly raised in the juvenile diabetics irrespective of the diabetes duration. (f) Fasting serum growth hormone levels were also significantly decreased during regulation. Furthermore, a significant correlation between blood glucose and fasting serum growth hormone concentration was established. (g) In the juvenile diabetics a significant increase in serum insulin was observed at the point of time when exercise was concluded.