Fructose Consumption and Metabolic Dysregulation

Hypertriglyceridemia Clinical Trial

Official title:

Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01445730
• Other study ID #: T1010K0029
• Status: Completed
• Phase: N/A
• Start date: August 2011
• Est. completion date: June 2015

Study information

• Verified date: May 2021
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

High fructose intake is increasingly recognized as causative in development of prediabetes, metabolic syndrome and cardiovascular disease (CVD). The mechanisms underlying fructose-induced metabolic disturbances are unclear but are beginning to be unraveled. In contrast to metabolism of glucose, the breakdown of fructose leads to the generation of metabolites that stimulate hepatic de novo lipogenesis (DNL) and increased levels of both fasting and postprandial triglycerides. The key lipogenic transcription factor seems to be activated by fructose independently of insulin. However, it is still controversial whether fructose consumption increases DNL in man to the extent that it induces metabolic disturbances. Animal studies have shown that also the adipose tissue is responsive to fructose feeding fructose, and that high fructose-feeding induces insulin resistance and inflammation in the adipose tissue. The role of intestinal insulin resistance in fructose-induced dysmetabolism has not been studied in detail. The critical question is whether the metabolic disturbances are induced by calorie excess or by fructose per se.

Description:

Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet: 1. An oral fat load or a kinetic study with stable isotopes combined with an oral fat load. 2. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy ) 3. Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling 4. Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

• Body mass index 27-40
• Waist > 96 cm
• Age 20-60 years
• Male

Exclusion Criteria:

• Smoking
• Active health problems
• Contraindications to MRI scanning
• Bleeding tendency
• Abnormal liver or renal function tests
• Type 2 diabetes
• Evidence of metabolic or viral liver disease
• Alcohol intake > 21 units per week
• Chronic medication except ones needed for stable hypertension

Related Conditions & MeSH terms

• Central Obesity
• Hypertriglyceridemia
• Obesity, Abdominal

Intervention

Dietary Supplement:
• Fructose
3 month fructose diet 75 g/day

Locations

Country	Name	City	State
Canada	Université Laval	Québec
Finland	Helsinki University Central Hospital, Biomedicum	Helsinki
Italy	University of Naples, Federico II, and Faculty of Medicine	Naples
Sweden	Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital	Gothenburg

Sponsors (5)

Lead Sponsor	Collaborator
Marja-Riitta Taskinen	Laval University, Lund University, Sahlgrenska University Hospital, Sweden, University of Naples

Countries where clinical trial is conducted

Canada,  Finland,  Italy,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TG Plasma AUC	Before vs. after fructose challenge: Triglycerides (TG) plasma Area Under Curve (AUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Primary	B48 Plasma AUC	Before vs. after fructose challenge: apolipoprotein (apo)B48 plasma Area Under Curve (AUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Primary	TG Plasma iAUC	Before vs. after fructose challenge:Triglycerides (TG) plasma incremental Area Under Curve (iAUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Secondary	DNL	Before vs. after fructose challenge: de novo lipogenesis (DNL)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Secondary	ApoC-III	Before vs. after fructose challenge: Apolipoprotein C-III (ApoC-III)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Secondary	ß-OH Butyrate	Before vs. after fructose challenge: beta-OH butyrate (ß-OH butyrate)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Secondary	Liver Fat	Before vs. after fructose challenge	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)