Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1-Mediated Mechanism

Context: The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective: We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design: We studied 14 lean adolescents [four females; 15.9 +/- 1.6 years of age; body mass index (BMI), 21.8 +/- 2.2 kg/m(2)] and 23 adolescents with obesity (five females; 15.1 +/- 1.6 years of age; BMI, 34.5 +/- 4.6 kg/m(2)). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and beta-cell function [oral disposition index (oDI(cpep))]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDI(cpep) was evaluated by regression analysis. Results: Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P < 0.001) and GLP-1 (P < 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P < 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDI(cpep) (r(2) = 0.22, P = 0.009). Conclusion: Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1-mediated mechanism.