Lipids and Insulin Sensitivity

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

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:

1. 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.
2. 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. 1 test meal
2. 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.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance
• Intervention / Treatment: Dietary supplement: test meals with various fatty acid compositions

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University Medical Centre +

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saturated fatty acid test meal	Dietary supplement: test meals with various fatty acid compositions; Three different milkshakes with a U13C palmitate tracer added
Experimental: Monounsaturated fatty acid meal	Dietary supplement: test meals with various fatty acid compositions; Three different milkshakes with a U13C palmitate tracer added
Experimental: Polyunsaturated fatty acid meal	Dietary supplement: test meals with various fatty acid compositions; Three different milkshakes with a U13C palmitate tracer added

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.

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Ellen E Blaak, PhD, Prof, Maastricht University Medical Centre +

Publications and helpful links

General Publications

• Jans A, Konings E, Goossens GH, Bouwman FG, Moors CC, Boekschoten MV, Afman LA, Muller M, Mariman EC, Blaak EE. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity. Am J Clin Nutr. 2012 Apr;95(4):825-36. doi: 10.3945/ajcn.111.028787. Epub 2012 Feb 15.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: November 3, 2011
• First Posted (Estimate): November 8, 2011

Study Record Updates

• Last Update Posted (Estimate): November 8, 2011
• Last Update Submitted That Met QC Criteria: November 3, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Lipid metabolism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 08-3-030