Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

Study Overview
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Brief Summary
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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.

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

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

Intervention / Treatment
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* Other: Test meal


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral fructose load<br>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<br>* Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.<br>|

What is the study measuring?
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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 |