Effects of dietary macronutrient intake on insulin sensitivity and secretion and glucose and lipid metabolism in healthy, obese adolescents

J Clin Endocrinol Metab. 2005 Aug;90(8):4496-502. doi: 10.1210/jc.2005-0626. Epub 2005 May 31.


Context: Adolescent obesity is a serious public health concern.

Objective: The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake.

Patients and design: Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 +/- 0.3 yr; body mass index, 34 +/- 1 kg/m2; body fat, 42 +/- 1%) were studied twice after 7 d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO).

Main outcome measures and methods: Glucose metabolism, insulin sensitivity, and first- and second-phase insulin secretory indices were measured by stable isotope techniques and the stable labeled iv glucose tolerance test. The results were compared with those of previously studied lean adolescents.

Results: Obese adolescents increased first- and second-phase insulin secretory indices by 18 (P = 0.05) and 36% (P = 0.05), respectively, to maintain normoglycemia during the high-CHO diet because they failed to increase insulin sensitivity as did the lean adolescents. Regardless of diet, in obese adolescents, insulin sensitivity was half (P < 0.05) and first- and second-phase insulin secretory indices twice (P < 0.01), compared with the the corresponding values in lean subjects. In obese adolescents, gluconeogenesis increased by 32% during the low-CHO (high-fat diet) (P < 0.01).

Conclusion: In obese adolescents, insulin secretory demands were increased regardless of diet. Failure to increase insulin sensitivity while receiving a high-CHO diet required a further increase in insulin secretion, which may lead to earlier beta-cell failure. A low-CHO/high-fat diet resulted in increased gluconeogenesis, which may be a prelude to the increased glucose production and hyperglycemia observed in type 2 diabetics.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Cross-Over Studies
  • Dietary Carbohydrates / pharmacokinetics*
  • Dietary Fats / pharmacokinetics*
  • Energy Metabolism / physiology
  • Female
  • Gluconeogenesis / physiology
  • Glycolysis / physiology
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Kinetics
  • Lipids / blood
  • Male
  • Obesity / metabolism*
  • Oxidation-Reduction


  • Blood Glucose
  • C-Peptide
  • Dietary Carbohydrates
  • Dietary Fats
  • Insulin
  • Lipids