The incidence and magnitude of hypoglycemia (i.e., blood glucose values less than 50 mg/dl) were assessed by continuous blood glucose monitoring over 24 h in 10 insulin-dependent diabetic (IDD) patients treated with continuous subcutaneous insulin infusion (CSII) and 9 IDD patients under intensified conventional treatment (ICT). A newly developed, battery-powered blood glucose monitor was employed. Patients were thus enabled to move freely in the hospital premises. Despite similar quality of previous blood glucose control (HbA1: 8.0 +/- 0.05% CSII versus 8.0 +/- 0.3% ICT, mean +/- SEM), the obtained profiles showed better regulation under CSII treatment (mean blood glucose [MBG], 99.6 +/- 10.0 versus 133.1 +/- 7.4 mg/dl; M-value, 12.3 +/- 3.5 versus 26.2 +/- 4.1; mean amplitude of glycemic excursion [MAGE], 71.9 +/- 8.7 versus 132.9 +/- 14.2 mg/dl; CSII versus ICT, mean +/- SEM). The incidence of blood glucose values less than 50 mg/dl was 9/10 patients (CSII) and 5/9 patients (ICT). In both groups, hypoglycemia was most frequent at noon and was related to elevated pre- and postprandial free insulin levels. Patients became aware of hypoglycemia only in 6/23 episodes (CSII) and 6/8 episodes (ICT). Our data indicate that CSII as well as ICT may result in postprandial hyperinsulinemia leading to frequent hypoglycemic episodes of variable length, reassessing the traditional experience of close correlation between aggressive insulin therapy and enhanced hypoglycemic risk.
SMS 201-995 is a new somatostatin analog which is 10-60 times more potent and specific than somatostatin as an inhibitor of GH and insulin release. The aim of this study was to assess its value as an adjunct to insulin therapy in insulin-dependent diabetic- (IDD) patients. Six IDD patients were studied. Their average insulin doses ranged from 22-46 U/day, and hemoglobin A1c levels varied between 6.5-11.5%. Two patients had background retinopathy and mild sensorimotor neuropathy. After 12 h of glucemic stabilization, the patients were kept normoglycemic by connecting them to the Biostator-GCIIS. The study entailed two parts in random order, in which standardised mixed meals were administered at 0800, 1400, and 2000 h with or without sc bolus injections of 50 micrograms SMS 201-995 immediately before meal ingestion. Plasma free insulin, C-peptide, GH, and glucagon were measured by RIA. Postprandial hyperglycemia was significantly diminished by SMS 201-995 after breakfast, lunch, and dinner. Insulin requirements, both total and 2-h postprandially, decreased significantly with a parallel reduction in free insulin levels. Postprandial glucagon levels also significantly decreased, but GH profiles were similar. In conclusion, the somatostatin analog SMS 201-995 has a potential value as an adjunct to insulin in the management of IDD patients.
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