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Continuous subcutaneous octreotide infusion: Dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes

Journal of Laboratory and Clinical Medicine
Publication Date
  • Medicine


Abstract Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 μg; high dose, 400 μg) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000–0800 hours) serum glucose levels decreased significantly ( p < 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly ( p < 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean ± SEM, 1000 ± 101, range 638 to 1375 pg/ml; high, mean 1940 ± 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 ± 0.30, range 1.31 to 3.78 ml/kg/ min; high, mean 2.36 ± 0.19, range 1.68 to 3.48 ml/kg/min). Steady-state analogue levels correlated significantly with serum glucose ( r = −0.523, p < 0.05), serum free insulin ( r = 0.739, p < 0.01), and glucagon ( r = −0.541, p < 0.05), but not with GH levels. In addition, MCR values correlated negatively with body weight ( r = −0.538, p < 0.05), but not with the metabolic parameters. In summary, this study demonstrates that C peptide-negative type 1 diabetic patients manifest great interindividual variability with regard to both plasma levels and MCR of octreotide that appears to be weight dependent. Finally, our study shows that (1) octreotide exhibits a threshold effect in suppressing both GH and glucagon release; (2) the partial suppression of both hormones, especially during high-dose therapy with the analogue, attests to the severity of regulatory derangement in type 1 diabetes; and (3) both pancreatic alpha and pituitary somatotropic cells appear to be resistant to the maximal inhibitory effect of the analogue in type 1 diabetes.

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