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.
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.
Carroll
P V
PV
Division of Medicine, St Thomas' Hospital, City University, London, UK.
Christ
E R
ER
Umpleby
A M
AM
Gowrie
I
I
Jackson
N
N
Bowes
S B
SB
Hovorka
R
R
Croos
P
P
Sönksen
P H
PH
Russell-Jones
D L
DL
D000328:Adult; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D004573:Electrolytes; D005215:Fasting / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D057947:Parenteral Nutrition Solutions; D011506:Proteins / Q000378:metabolism; D012996:Solutions
D000596:Amino Acids; D004573:Electrolytes; D007004:Hypoglycemic Agents; D007328:Insulin; D057947:Parenteral Nutrition Solutions; D011506:Proteins; D012996:Solutions; C545824:amino-acid, glucose, and electrolyte solution; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose