Effects of puberty and diabetes on metabolism of insulin-sensitive fuels.
Insulin's ability to stimulate glucose metabolism is reduced during normal puberty; these changes are exaggerated in adolescents with insulin-dependent diabetes mellitus (IDDM). Because the effects of puberty and IDDM on the other actions of insulin have not been established, we studied leucine kinetics (using [1-13C]leucine) and fat metabolism during euglycemic hyperinsulinemia (20 mU.m2.min-1) for 3 h in eight healthy and nine IDDM (HbA1 14 +/- 2%) adolescents and six healthy young adult controls. IDDM subjects received overnight low-dose insulin infusion to normalize fasting glucose. Basal and steady-state insulin values (approximately 240 pM) during the study were similar in all three groups. Insulin-stimulated glucose metabolism was reduced by 40% in healthy adolescents vs. adults (P < 0.05) and by an additional 40% in poorly controlled IDDM (P < 0.05 vs, normal adolescents). Although basal glucose and lipid oxidation rates (measured by indirect calorimetry) were similar in all three groups, when insulin was infused, glucose oxidation increased and lipid oxidation decreased only in the two nondiabetic groups. Similarly, insulin significantly reduced plasma free fatty acid levels only in the nondiabetics. Basal leucine flux (an index of protein degradation) was similar in healthy controls but was markedly increased in IDDM adolescents. Despite similar increments in plasma insulin during the clamp, leucine flux remained higher in IDDM adolescents than in healthy controls. Basal leucine oxidation rates were also increased in IDDM subjects compared with nondiabetic groups and declined to a lesser extent during insulin infusion. We conclude that insulin resistance of puberty is selective for glucose metabolism, sparing amino acid/protein metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Caprio
S
S
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Cline
G
G
Boulware
S
S
Permanente
C
C
Shulman
G I
GI
Sherwin
R S
RS
Tamborlane
W V
WV
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000097:blood; D001158:Arteries; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism*; D011627:Puberty / Q000502:physiology*
D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011506:Proteins; D007930:Leucine; D005947:Glucose