Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

NCT02979106 | Completed

• 1 other identifier: PB_2016-00289 (302/14)
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: High fructose intake increases blood lactate, triglyceride and uric acid concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the general population. In patients with hereditary fructose intolerance fructose consumption is associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia. Objective: We investigated whether asymptomatic carriers for hereditary fructose intolerance (HFI) would have a higher sensitivity to adverse effects of fructose than the general population. Design: Eight subjects heterozygous for HFI (hHFI; 4 males, 4 females) and eight controls received for 7 days a low fructose diet and on the eighth day ingested a test meal calculated to provide 25% of basal energy requirement containing labeled fructose (13C fructose 0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg). Total fructose oxidation, total endogenous glucose production (by 6,6-2H2-glucose dilution), carbohydrate and lipid oxidation, lipids, uric acid, lactate, creatinine, urea and amino acids were monitored for 6 hours.

Conditions

Hereditary Fructose Intolerance; Fructose Metabolism, Inborn Errors; Glucose Metabolism Disorders

Outcome Measures

Primary Outcomes (1)

• Plasma glucose kinetics

  Modelling of rate of glucose appearance after administration of a bolus of 6,6-2H2 glucose (bolus, 2 mg/kg and continuous infusion, 0.02 mg/kg/min) will be measured in fasted and fed conditions

  -120 min before ingestion of a test meal to 360 min after ingestion of a test meal

Secondary Outcomes (5)

• Energy expenditure rate

  120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

• Glucose oxidation rate

  120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

• Plasma glucose concentration

  -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

• plasma insulin concentration

  -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

• Fructose oxidation

  Every 30 min until 360 min after ingestion of a test meal

Study Arms (1)

oral fructose load

EXPERIMENTAL

test meal calculated to provide 25% of basal energy requirement containing 13C-labeled fructose (0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg).

Other: Test meal

Interventions

Test meal OTHER

Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.

oral fructose load

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy Volunteers (4 male, 4 female) parents of a child with hereditary fructose intolerance with ALDOB with heterozygous mutation of ALDOB gene
• healthy Volunteers (4 male, 4 female), healthy with no mutation of ALDOB gene

You may not qualify if:

• Fasting glycemia \> 7.0 mmol/L
• Fasting total triglycerides \> 4.0 mmol/L
• Chronic renal insufficiency (eGFR ≤ 50 ml/min)
• Anemia (ferritin \< 20 ug/L, hemoglobin \< 13.5 ou 12.5 g/dl)
• Drugs
• Pregnancy

Sponsors & Collaborators

• University of Lausanne: lead

Related Publications (1)

• Debray FG, Damjanovic K, Rosset R, Mittaz-Crettol L, Roux C, Braissant O, Barbey F, Bonafe L, De Bandt JP, Tappy L, Paquot N, Tran C. Are heterozygous carriers for hereditary fructose intolerance predisposed to metabolic disturbances when exposed to fructose? Am J Clin Nutr. 2018 Aug 1;108(2):292-299. doi: 10.1093/ajcn/nqy092.

  PMID: 29955837 DERIVED

MeSH Terms

Conditions

Fructose Intolerance; Fructose Metabolism, Inborn Errors; Glucose Metabolism Disorders

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Tappy Luc, MD

  University of Lausanne

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: December 1, 2016
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: November 1, 2016
• Last Updated: July 17, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share