Summary
We investigated the respective roles of insulin deprivation and counter-regulatory hormones in the metabolic deterioration after a nocturnal interruption of continuous subcutaneous insulin infusion in Type 1 (insulin-dependent) diabetic patients without residual insulin secretion. Changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon, growth hormone, cortisol and free insulin in seven patients whose pumps were deliberately stopped between 23.00 h and 05.00 h were compared in two randomized tests carried out either during an intravenous somatostatin infusion at a constant rate of 250 μg/h from 22.00 h until 07.00 h (somatostatin test) or during a saline infusion (control test). Arrest of the pumps resulted in a rapid (already significant after 1 h) and progressive (nadir after 5–6 h) decrease in plasma free insulin concentrations with no statistically significant differences between the two tests. Somatostatin remarkably depressed basal levels of growth hormone and the late significant increase in glucagon (+39±14 pg/ml at 05.00 h, 2p< 0.05) observed during the control test. In contrast, cortisol secretion was not inhibited. The sharp linear increase in blood glucose observed from 01.00 to 05.00 h (38±4 μmol·l-1· min-1) in the control test was fully suppressed with a paradoxical tendency to hypoglycaemia until 03.00 h and a less steep rise from 03.00 to 05.00 h (18±5 μmol·l-1·min-1, 2p<0.05) during the somatostatin test. Initial plasma non-esterified fatty acids levels were slightly higher on somatostatin but did not show any statistically significant rise despite arrest of the pump, contrasting with the increase from 491±27 to 741±96 μmol/l (2p<0.05) in the control test. Consequently, plasma non-esterified fatty acids levels from 01.00 to 05.00 h were not significantly different between the two tests. The abrupt rise in 3-hydroxybutyrate from 00.00 to 05.00 h (3.0±0.5 μmol·l-1·min-1) in the control test was not altered by somatostatin until 03.00 h. In contrast, during the last 2 h after arrest of the pump, somatostatin inhibited any further rise in 3-hydroxybutyrate levels. In conclusion, somatostatin significantly reduces metabolic deterioration during a 6-h nocturnal interruption of a continuous subcutaneous insulin infusion. Somatostatin-induced glucagon suppression seems to be involved in reducing hyperglycaemia as well as, together with the somatostatin-induced growth hormone suppression, in the limitation of hepatic ketogenesis in hours 5 and 6 after cessation of insulin supply. In contrast, the early rise in 3-hydroxybutyrateplasma levels is unaffected by somatostatin and thus appears entirely due to the fall in free insulin circulating concentrations.
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Scheen, A.J., Krzentowski, G., Castillo, M. et al. A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 2. Marked attenuation of the metabolic deterioration by somatostatin. Diabetologia 24, 319–325 (1983). https://doi.org/10.1007/BF00251816
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DOI: https://doi.org/10.1007/BF00251816