Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

Not Applicable

Completed

• Conditions: Hereditary Fructose Intolerance; Fructose Metabolism, Inborn Errors; Glucose Metabolism Disorders
• Interventions: Other: Test meal

• Registration Number: NCT02979106
• Lead Sponsor: University of Lausanne

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Primary Completion: 2016-01
• Study Completion: 2016-11
• Study First Submitted: 2016-11-14
• Study First Submitted QC: 2016-11-28
• Study First Posted: 2016-12-01
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-15
• Last Update Posted: 2019-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
oral fructose load	Test meal	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).

Primary Outcome Measures

Name	Time	Method
Plasma glucose kinetics	-120 min before ingestion of a test meal to 360 min after ingestion of a test meal	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

Secondary Outcome Measures

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