Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2005
Publication Date: 9/20/2005
Citation: Sunehag, A.L., Toffolo, G., Camioni, M., Bier, D.M., Haymond, M.W. 2005. Effects of dietary macronutrient intake on insulin sensitivity and secretion and glucose and lipid metabolism in healthy, obese adolescents. Journal of Clinical Endocrinology & Metabolism. 90(8):4496-4502. Interpretive Summary: In agreement with previous reports, the healthy obese adolescents included in this study were highly insulin resistant, both in the overnight fasted state and in response to a glucose challenge. Importantly, however, our study also demonstrated that neither the fat nor the carbohydrate composition of the diet had any effect on the degree of insulin resistance. Thus, in order to maintain normal glucose and lipid concentrations, normal rates of glucose and lipolysis and appropriate substrate oxidation, obese adolescents required a twofold increase in their insulin secretion. In addition, during the high carbohydrate diet, obese adolescents failed to increase insulin sensitivity (as was observed in their lean counterparts) requiring them to further increase insulin secretion. Overtime, this additional demand on pancreatic beta cell function may contribute to early failure of the beta cells and subsequent type 2 diabetes.
Technical Abstract: Adolescent obesity is a serious public health concern. The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake. Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 +/- 0.3yr; body mas index, 34 +/- 1kg/m(2); 42 +/- 1%) were studied twice following 7d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO). 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. 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). 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.