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.

to Consider:

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