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

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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.

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