IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp

• Published in: Diabetes (New York, N.Y.) Vol. 49; no. 5; pp. 789 - 796
• Main Authors: CARROLL, P. V, CHRIST, E. R, UMPLEBY, A. M, GOWRIE, I, JACKSON, N, BOWES, S. B, HOVORKA, R, CROOS, P, SÖNKSEN, P. H, RUSSELL-JONES, D. L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.2000
• Subjects: Adult; Amino Acids - metabolism; Amino Acids - pharmacology; Biological and medical sciences; Circadian Rhythm; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - therapy; Electrolytes; Fasting - physiology; Female; General and cellular metabolism. Vitamins; Glucose - metabolism; Glucose Clamp Technique; Human Growth Hormone - metabolism; Humans; Hyperinsulinism - metabolism; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - therapeutic use; Male; Medical sciences; Middle Aged; Parenteral Nutrition Solutions; Pharmacology. Drug treatments; Proteins - metabolism; Solutions; Endocrinopathy; Human; Immunopathology; Chemotherapy; Treatment; Insulin dependent diabetes; Autoimmune disease; Subcutaneous administration; Glucose; Insulin like growth factor 1; Metabolism; Biological activity
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.49.5.789

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. P V Carroll , E R Christ , A M Umpleby , I Gowrie , N Jackson , S B Bowes , R Hovorka , P Croos , P H Sönksen and D L Russell-Jones Division of Medicine, St Thomas' Hospital, City University, London, UK. Abstract Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.