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

Abstract

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/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). 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)]. 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 oDIcpep 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 oDIcpep (r2 = 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.

• Authors: Alfonso Galderisi, Cosimo Giannini, Michelle Van Name, Sonia Caprio
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 8 Pg. 3481-3490 (08 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 30938760 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Endocrine Society.

Chemical References

• Insulin
• Sweetening Agents
• Fructose
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Glucose

Topics

• Adolescent
• Body Mass Index
• Cross-Over Studies
• Double-Blind Method
• Eating (physiology)
• Female
• Fructose (adverse effects)
• Gastric Inhibitory Polypeptide (blood)
• Glucagon-Like Peptide 1 (blood)
• Glucose (adverse effects)
• Glucose Tolerance Test
• Humans
• Hyperinsulinism (etiology)
• Insulin (blood)
• Male
• Pediatric Obesity (blood, complications, physiopathology)
• Postprandial Period
• Sweetening Agents (adverse effects)