Clinical trial NCT00523562: Effects of Macronutrients on Hepatic Lipids, Plasma Triglycerides, and Insulin Sensitivity
Official title: Study of the Role of Insulin Resistance in the Pathogenesis of the Metabolic Syndrome and of Non-alcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome X
Liver Diseases
Keywords: fructose
dietary lipids
dietary proteins
hepatic steatosis
insulin resistance
Healthy humans
overweight humans
obese humans
Lead sponsor: University of Lausanne
Sponsor class: OTHER
First posted: 2007-08-31
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess how the macronutrient composition of the diet effects

* lipid and glucose metabolism
* intrahepatic lipids
* insulin sensitivity

in healthy lean subjects and in subjects with a high metabolic risk (ie overweight and offsprings of patients with type 2 diabetes mellitus).

Detailed description: The study is aimed at assessing the effects of changes in total energy, sugars, lipids, and protein intake on intrahepatic lipids, plasma lipids, and hepatic and whole body insulin resistance in

* lean men and women with no family history of diabetes
* overweight men and women
* lean men with a family history of type 2 diabetes

Subjects are studied after a 6-day period of

* isocaloric diet with 100% calorie requirement, of which 55% carbohydrate, 15% protein, and 30% fat)
* the same isocaloric diet supplemented with 3g/kg body weight/day fructose
* hypercaloric high fat diet with 130% energy requirement, of which 55% carbohydrate, 15% protein, 60% fat
* hypercaloric high fat+protein diet with 145% energy requirement, of which 55% carbohydrate, 30% protein, 60% fat

Measurements performed after 6 days on each diet include

* intrahepatic and intramyocellular lipids (1H-MRS)
* hepatic and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp)
* body weight
* plasma concentrations of hormones and substrates
* gene expression profile in skeletal muscle (vastus lateralis) and adipose tissue (subcutaneous abdominal)

Eligibility criteria: Inclusion Criteria:

* Males and females
* Age 18-40
* Informed consent obtained
* Subgroup with overweight (body mass index \[BMI\] \> 25)
* Subgroup with family history of type 2 diabetes mellitus

Exclusion Criteria:

* Smokers
* Alcohol intake \> 30g/day
* Drug abuse
* Diabetes mellitus
* Any concurrent medication
* Having a pacemaker
* History of orthopedic surgery
* History of metal foreign bodies

Primary outcomes:
measure: plasma triglycerides
timeFrame: 6 days
measure: intra-hepatic lipids
timeFrame: 6 days
measure: insulin mediated glucose disposal
timeFrame: 6 days
Secondary outcomes:
measure: lipid oxidation
timeFrame: 6 days
measure: plasma beta-hydroxybutyrate
timeFrame: 6 days
measure: gene expression in skeletal muscle and adipose tissue
timeFrame: 6 days
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: University of Lausanne
name: Luc Tappy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, Ith M, Vermathen P, Stefanoni N, Le KA, Schneiter P, Krempf M, Vidal H, Boesch C, Tappy L. High protein intake reduces intrahepatocellular lipid deposition in humans. Am J Clin Nutr. 2009 Oct;90(4):1002-10. doi: 10.3945/ajcn.2008.27296. Epub 2009 Aug 26.
citation: Le KA, Ith M, Kreis R, Faeh D, Bortolotti M, Tran C, Boesch C, Tappy L. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr. 2009 Jun;89(6):1760-5. doi: 10.3945/ajcn.2008.27336. Epub 2009 Apr 29.