INDUCTION OF BETA-CELL REST IN TYPE-1 DIABETES - STUDIES ON THE EFFECTS OF OCTREOTIDE AND DIAZOXIDE

OBJECTIVE- To evaluate the inhibitory effects of octreotide and diazox ide on insulin secretion in patients with type 1 diabetes and measurab le levels of circulating C-peptide. RESEARCH DESIGN AND METHODS- Diazo xide was given to six patients during a 7-day period (100 mg three tim es daily), followed by a 3-week washout. Subsequently, octreotide (50 mu g, three times daily) was administered subcutaneously for 7 days. P re- and postprandial blood glucose and serum C-peptide concentrations were measured before medication (control) and on day 7 of each medicat ion period. Glucagon-stimulated C-peptide was determined in the mornin g before medication and on the day after each treatment period. RESULT S- Diazoxide inhibited glucagon-stimulated C-peptide secretion (mean i ncrement 0.08 nmol/l vs. 0.18 nmol/l, P < 0.05), whereas octreotide ha d no such effect. Both reduced the pre-and postprandial serum C-peptid e concentrations (P < 0.05), octreotide being the more potent in this respect. A reduction in basal and meal-related blood glucose was obser ved during octreotide treatment, whereas the glucose concentrations te nded to be higher during treatment with diazoxide than during the 24-h control period. CONCLUSIONS- The study indicates that the two drugs r educe insulin output by different mechanisms. Diazoxide inhibits hormo nal release directly on the beta-cells, whereas octreotide exerts its effect indirectly, presumably by multiple actions on insulin sensitivi ty and insulin-releasing hormones. The results suggest that each drug is capable of inducing beta-cell rest in type 1 diabetes.