Fructose Metabolism, Inborn Errors, Glucose Metabolism Disorders, Hereditary Fructose Intolerance
Conditions
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.
Interventions
OTHERTest meal
Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.
Sponsors
University of Lausanne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Fructose oxidation | Every 30 min until 360 min after ingestion of a test meal | Fructose oxidation is measured from 13CO2 production |
Outcome results
None listed