Combination of continuous subcutaneous infusion of insulin and octreotide in Type 1 diabetic patients

Abstract

The effect of 7 day continuous subcutaneous infusion of octreotide (200 μg day −1) was evaluated in seven insulin-pump treated Type 1 diabetic patients (age 43±1.5 year; BMI 25.1±0.7 kg m −2; HbA 1c 7.4±0.3%). A 24-h metabolic and hormonal profile, and a euglycaemic hyperinsulinaemic clamp (0.25, 0.5, 1.0 mg kg −1 min −1), with [ 3H]glucose infusion and indirect calorimetry, were performed before and after a 7-day octreotide infusion. Mean 24-h plasma glucose was similar before and after octreotide (9.7±0.8 vs. 9.1±1.0 mmol l −1) but insulin requirement dropped by 45% (49±4 vs. 27±2 U day −1; P<0.01). Both 24-h plasma hGH and glucagon were suppressed by octreotide (1.85±0.35 vs. 0.52±0.04 μg l −1, and 117±23 vs. 102±14 ng l −1, respectively). Glucose utilisation increased after octreotide (insulin 0.5 mU kg −1 min −1 clamp 3.09±0.23 vs. 4.19±0.19 mg kg −1 min −1; 1 mU kg −1 min −1 clamp 5.64±0.61 vs. 7.93±0.57 mg kg −1 min −1; both P<0.05) and endogenous glucose production was similarly suppressed. Glucose oxidation was not affected by octreotide, while the improvement in glucose storage (insulin 1.0 mU kg −1 min −1 clamp 3.89±0.60 vs. 5.64±0.67 mg kg −1 min −1, P<0.05) entirely accounted for the increase in glucose disposal. Endogenous glucose production was more effectively suppressed at the two lower insulin infusion rates ( P>0.05). Energy expenditure declined after octreotide. Continuous subcutaneous octreotide infusion suppresses counterregulatory hormones, increases insulin-mediated glucose metabolism by enhancing glucose storage, and reduces energy expenditure. These results support a role for counterregulatory hormones in the genesis of insulin resistance and the catabolic state of Type 1 diabetes.