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Induction of β-Cell Rest in Type 1 Diabetes: Studies on the effects of octreotide and diazoxide

  1. Elisabeth Björk, MD, PHD,
  2. Christian Berne, MD, PHD and
  3. F Anders Karlsson, MD, PHD
  1. Department of Medicine, University Hospital Uppsala, Sweden
  1. Address correspondence and reprint requests to Anders Karlsson, Section of Endocrinology and Diabetes, Department of Medicine, University Hospital, S-751 85 Uppsala, Sweden. E-mail: anders.karlsson{at}medicin.uu.se

Abstract

OBJECTIVE To evaluate the inhibitory effects of octreotide and diazoxide on insulin secretion in patients with type 1 diabetes and measurable levels of circulating C-peptide.

RESEARCH DESIGN AND METHODS Diazoxide was given to six patients during a 7-day period (100 mg three times daily), followed by a 3-week washout. Subsequently, octreotide (50 micrograms, three times daily) was administered subcutaneously for 7 days. Pre- and post- prandial blood glucose and serum C-peptide concentrations were measured before medication (control) and on day 7 of each medication period. Glucagon-stimulated C-peptide was determined in the morning before medication and on the day after each treatment period.

RESULTS Diazoxide inhibited glucagon-stimulated C-peptide secretion (mean increment 0.08 nmol/l vs. 0.18 nmol/l, P < 0.05), whereas octreotide had no such effect. Both reduced the pre- and postprandial serum C-peptide concentrations (P < 0.05), octreotide being the more potent in this respect. A reduction in basal and meal-related blood glucose was observed during octreotide treatment, whereas the glucose concentrations tended to be higher during treatment with diazoxide than during the 24-h control period.

CONCLUSIONS The study indicates that the two drugs reduce insulin output by different mechanisms. Diazoxide inhibits hormonal release directly on the beta-cells, whereas octreotide exerts its effect indirectly, presumably by multiple actions on insulin sensitivity and insulin-releasing hormones. The results suggest that each drug is capable of inducing beta-cell rest in type 1 diabetes.

  • Received July 18, 1997.
  • Accepted November 12, 1997.
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