EFFECTS OF PUBERTY AND DIABETES ON METABOLISM OF INSULIN-SENSITIVE FUELS

Insulin's ability to stimulate glucose metabolism is reduced during no rmal puberty; these changes are exaggerated in adolescents with insuli n-dependent diabetes mellitus (IDDM). Because the effects of puberty a nd IDDM on the other actions of insulin have not been established, we studied leucine kinetics (using [1-C-13]leucine) and fat metabolism du ring euglycemic hyperinsulinemia (20 mU.m(2).min(-1)) for 3 h in eight healthy and nine IDDM (HbA(1) 14 +/- 2%) adolescents and six healthy young adult controls. IDDM subjects received overnight low-dose insuli n infusion to normalize fasting glucose. Basal and steady-state insuli n values (similar to 240 pM) during the study were similar in all thre e 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 bas al glucose and lipid oxidation rates (mea sured by indirect calorimetr y) were similar in all three groups, when insulin was infused, glucose oxidation increased and lipid oxidation decreased only in the two non diabetic groups. Similarly, insulin significantly reduced plasma free fatty acid levels only in the nondiabetics. Basal leucine flux (an ind ex of protein degradation) was similar in healthy controls but was mar kedly increased in IDDM adolescents. Despite similar increments in pla sma insulin during the clamp, leucine flux remained higher in IDDM ado lescents than in healthy controls. Basal leucine oxidation rates were also increased in IDDM subjects compared with nondiabetic groups and d eclined to a lesser extent during insulin infusion. We conclude that i nsulin resistance of puberty is selective for glucose metabolism, spar ing amino acid/protein metabolism. On the other hand, in adolescents w ith IDDM, the combined effects of puberty and poorly controlled diabet es produce more profound generalized metabolic defects that include pr oteolysis.