Effects of Macronutrients on Hepatic Lipids, Plasma Triglycerides, and Insulin Sensitivity

Study Overview
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Brief Summary
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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
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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)

Official Title
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Study of the Role of Insulin Resistance in the Pathogenesis of the Metabolic Syndrome and of Non-alcoholic Steatohepatitis

Conditions
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Metabolic Syndrome X, Liver Diseases

Intervention / Treatment
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* Other: diet intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: normal weight male high fructose diet<br>Effects of diet intervention  high fructose in normal weight subjects | Other: diet intervention<br>* controlled hypercaloric high fructose, high fat, or high fat/high protein diet<br>|
| Experimental: offsprings of T2DM high fructose diet<br>Effect of diet intervention high fructose in healthy non-obese offsprings of patients with type 2 diabetes | Other: diet intervention<br>* controlled hypercaloric high fructose, high fat, or high fat/high protein diet<br>|
| Experimental: normal weight subjects high fat diet<br>effects of diet intervention high fat in healthy male subjects | Other: diet intervention<br>* controlled hypercaloric high fructose, high fat, or high fat/high protein diet<br>|
| Experimental: Normal weight high fat+protein diet<br>effect of diet intervention high fat + protein subjects in healthy male subjects | Other: diet intervention<br>* controlled hypercaloric high fructose, high fat, or high fat/high protein diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma triglycerides |  | 6 days | 
| intra-hepatic lipids |  | 6 days | 
| insulin mediated glucose disposal |  | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lipid oxidation |  | 6 days | 
| plasma beta-hydroxybutyrate |  | 6 days | 
| gene expression in skeletal muscle and adipose tissue |  | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fructose, dietary lipids, dietary proteins, hepatic steatosis, insulin resistance, Healthy humans, overweight humans, obese humans