Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

Are Heterozygous Carriers for Hereditary Fructose Intolerance Predisposed to Metabolic Disturbances When Exposed to Fructose?

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.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Fructose Metabolism, Inborn Errors; Hereditary Fructose Intolerance
• Intervention / Treatment: Other: Test meal

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral fructose load; 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; Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Energy expenditure rate	Energy expenditure is measured by indirect calorimetry in fasted and fed conditions	120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
Glucose oxidation rate	glucose oxidation is measured by indirect calorimetry in fasted and fed conditions	120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
Plasma glucose concentration	plasma glucose concentration measured by glucose oxidase	-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
plasma insulin concentration	Plasma insulin concentration measured by ELISA	-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
Fructose oxidation	Fructose oxidation is measured from 13CO2 production	Every 30 min until 360 min after ingestion of a test meal

Collaborators and Investigators

• Sponsor: University of Lausanne
• Investigators: Study Director: Tappy Luc, MD, University of Lausanne

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: November 14, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Fructose Intolerance; Metabolism, Inborn Errors; Metabolic Diseases; Glucose Metabolism Disorders; Fructose Metabolism, Inborn Errors
• Other Study ID Numbers: PB_2016-00289 (302/14)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No