Combination of continuous subcutaneous infusion of insulin and octreotide in Type 1 diabetic patients.
The effect of 7 day continuous subcutaneous infusion of octreotide (200 microg 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 microg 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.
Bruttomesso
D
D
Department of Clinical and Experimental Medicine, Cattedra di Malattie del Metabolismo, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
Fongher
C
C
Silvestri
B
B
Barberio
S
S
Marescotti
M C
MC
Iori
E
E
Valerio
A
A
Crazzolara
D
D
Pianta
A
A
Tiengo
A
A
Del Prato
S
S
D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006728:Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D007773:Lactates / Q000097:blood; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*
D000409:Alanine; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D006728:Hormones; D019382:Human Growth Hormone; D007328:Insulin; D007773:Lactates; D015282:Octreotide