Lipids and Insulin Sensitivity

Study Overview
=================
Brief Summary
-----------------
Rationale: The investigators hypothesize that a change in dietary fat quality (an increase in unsaturated fatty acids) may modulate fuel partitioning within the type 2 diabetic muscle towards less accumulation of lipid metabolites and an improved insulin sensitivity. Objective: The contribution of dietary vs endogenous fat sources to lipid overflow in the circulation and to skeletal muscle lipid uptake and storage in obese insulin resistant subjects vs obese insulin sensitive controls. The acute effect of meals with various fatty acid composition ((high saturated (SFA) vs polyunsaturated (PUFA) vs monounsaturated (MUFA)) on skeletal muscle lipid uptake and storage, fatty acid mediated gene expression and postprandial insulin sensitivity in obese insulin resistant subjects. Study design: single-blind randomized cross-over trial Study population: obese males (35-70 years) with or without insulin resistance Intervention: 1 test meal 3 test meals with a different fatty acid composition Main study parameters/endpoints: More insight whether dietary fat quality may modulate circulating lipids and skeletal muscle fatty acids handling, and may affect oxidative capacity and lipid storage in parallel to an increased insulin sensitivity.

Official Title
-----------------
Skeletal Muscle Lipid Metabolism and Insulin Sensitivity: Can Dietary Fatty Acid Composition Modulate Muscle Lipid Storage?

Conditions
-----------------
Obesity, Insulin Resistance

Intervention / Treatment
-----------------
* Dietary Supplement: test meals with various fatty acid compositions


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese males aged between 35 and 70 years with insulin resistance. Exclusion Criteria: History of type 2 diabetes. Liver or kidney failure. Diseases in which the live expectation is shorter then 5 years. The use of experimental medication. Diseases/medication use that may have an influence on the glucose tolerance. Not to be able to understand the study information. Users of fatty acid supplements including fish oils etc. Users of high doses of antioxidant vitamins. Athletes. People on a diet of people that are planning to lose weight.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saturated fatty acid test meal<br> | Dietary Supplement: test meals with various fatty acid compositions<br>* Three different milkshakes with a U13C palmitate tracer added<br>|
| Experimental: Monounsaturated fatty acid meal<br> | Dietary Supplement: test meals with various fatty acid compositions<br>* Three different milkshakes with a U13C palmitate tracer added<br>|
| Experimental: Polyunsaturated fatty acid meal<br> | Dietary Supplement: test meals with various fatty acid compositions<br>* Three different milkshakes with a U13C palmitate tracer added<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute effect of meals with various fatty acid composition on postprandial insulin sensitivity | The acute effect of meals with various fatty acid composition ((high saturated (SFA) vs polyunsaturated (PUFA) vs monounsaturated (MUFA)) on postprandial insulin sensitivity will be measured during the stable isotope test. | the individual participants will be measured within 8-10 weeks. | 
| Acute effect of meals with various fatty acid composition on forearm muscle fatty acid handling | Using the stable isotope technique, we can differentiate between the metabolic fate of dietary versus endogenous fatty acids | the individual participants will be measured within 8-10 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute effect of meals with various fatty acid composition on intramuscular fatty acid handling |  | the individual participants will be measured within 8-10 weeks. | 
| Acute effect of meals with various fatty acid composition on transcriptional regulation of the fatty acid metabolism in skeletal muscle biopsies | Transcriptional regulation will be measured by means of microarray. | the individual participants will be measured within 8-10 weeks. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lipid metabolism