Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

University of Lausanne18 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Hereditary Fructose Intolerance Fructose Metabolism, Inborn Errors

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

Energy expenditure rate

Energy expenditure is measured by indirect calorimetry in fasted and fed conditions

Time frame: 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

Time frame: 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

Time frame: -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

Time frame: -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

Time frame: Every 30 min until 360 min after ingestion of a test meal