Effects of the somatostatin analog, octreotide, on glucose metabolism and insulin sensitivity in insulin-dependent diabetes mellitus

To examine the effect of the somatostatin analog, octreotide, on insulin-mediated glucose uptake, seven insulin-dependent diabetic (IDDM) subjects were studied with and without 4 days of continuous subcutaneous octreotide administration (1 μg/kg/d). Insulin dosage was adjusted after frequent measurements of plasma glucose level. On the third day a hormonal and metabolic blood profile was obtained, and on the fourth day a euglycemic (5 mmol/L), hyperinsulinemic (1 mU/kg/min) clamp was performed in combination with calorimetry and a muscle biopsy. Mean plasma glucose levels on day 3 were similar (7.9 ± 0.9 v 9.0 ± 0.6 mmol/L). Growth hormone (GH) (0.39 ± 0.10 v 0.78 ± 0.23 μg/L, P < .05), insulin-like growth factor-I (IGF-I) (127 ± 17 v 157 ± 21 μg/L, P < .05), and nonesterified fatty acids (NEFA) (239 ± 25 v 405 ± 44 μmol/L, P < .01) were lower following octreotide administration. Insulin requirements were reduced during octreotide administration, resulting in significantly lower insulin levels (27.3 ± 2.7 v 39.9 ± 9.9 mU/L, P < .5). During the clamp, glucose and insulin levels were similar. Following octreotide, glucose disposal (7.33 ± 0.49 v 6.08 ± 0.55 mg/kg/min, P < .05) increased and hepatic glucose production (HGP) was more suppressed (−1.56 ± 0.07 v −0.63 ± 0.34 mg/kg/min, P < .05, 220 to 270 minutes). Oxidative glucose disposal (indirect calorimetry) was enhanced (3.09 ± 0.24 v 2.70 ± 0.37 mg/kg/min, P = .08), whereas glucose storage, as well as the fractional velocity for glycogen synthase activity, were unaltered during octreotide administration. Conversely, octreotide decreased lipid oxidation (0.12 ± 0.1 v 0.41 ± 0.15 mg/kg/min, P < .05). In conclusion, a low-dose octreotide infusion for 4 days to IDDM subjects leads to significantly increased insulin sensitivity.