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

J Clin Endocrinol Metab. 2019 Aug 1;104(8):3481-3490. doi: 10.1210/jc.2019-00161

Galderisi A, Giannini C, van Name M, et al.

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  • To test the hypothesis that that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity.


  • 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.
  • It is unclear whether the same or similar effect occurs in lean and obese adolescents.


  • Fourteen lean adolescents and twenty-three obese adolescents were included in the study. The average BMI was approximately 22 in the lean group and approximately 35 in the obese group.  The average age in both groups was approximately 16. 
  • Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. In a double-blind, crossover design, eligible subjects received 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 oDIcpep was evaluated by regression analysis.


  • Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents in the obese group 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 oDIcpep.


  • 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.

Points to Consider:

  • Given the small size and age of the sample, the generalizability of these results is limited.