The Effect of Lowered Physical Activity on Insulin Sensitivity and Lipid and Glucose Metabolism

NCT01576250 | Completed

• 1 other identifier: NL38795.068.11/METC 11-3-074
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effects of lowered physical activity (resulting in decreased muscle mitochondrial oxidative capacity) alone and together with increased plasma free fatty acid availability (by infusion of a clinically widely used lipid emulsion (Intralipid)) on insulin sensitivity and glucose and lipid metabolism. To this end, we will compare skeletal muscle insulin sensitivity and glucose and lipid metabolism (within one subject) after 9 days of immobilization of one leg (unilateral lower limb suspension(ULLS))(decreased muscle mitochondrial oxidative capacity) versus an active control leg (unchanged muscle mitochondrial oxidative capacity). Further, changes in IMCL and fatty acid intermediates will be investigated in the immobilized vs the control leg, and this will be related to insulin sensitivity. The effectiveness of the ULLS intervention will be tested by measuring muscle mitochondrial oxidative capacity in both the immobilized and the control leg. All measurements will be performed both in the immobilized and control leg after 9 days of ULLS.

Conditions

Insulin Sensitivity

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Insulin sensitivity will further be investigated from the skeletal muscle tissue ex vivo.

  after 9 days of ULLS

Secondary Outcomes (4)

• intramyocellularlipid content

  after 9 days of ULLS

• Lipid intermediates

  after 9 days of ULLS

• Lipid metabolism

  after 9 days of ULLS

• Glucose metabolism

  after 9 days of ULLS

Study Arms (1)

unilateral lower limb suspension

EXPERIMENTAL

This is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking.

Other: unilateral lower limb suspension

Interventions

unilateral lower limb suspension OTHER

This is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking.

unilateral lower limb suspension

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men between 18-35 years of age at time of enrolment
• Non smoking
• No recent bone fractures of the limbs
• No cardiovascular medication or other medication
• No family history of thrombosis
• No engagement in programmed exercise for more than two hours a week
• Stable dietary habits
• No contra-indication for MRI

You may not qualify if:

• Regular smokers
• Participation in other studies
• Female sex
• Recent bone fractures of the limbs
• Medication use
• Cardiovascular disease
• Family history of type 2 diabetes mellitus
• Family history of thrombosis
• Contraindications for MRS scans:
• Electronic implants such as pacemakers or neurostimulator
• Iron-containing foreign bodies in eyes or brain
• Some hearing aids and artificial (heart) valves which are contraindicated for MRS
• Claustrophobia
• Participants, who do not want to be informed about unexpected medical findings, or do not wish that their physician will be informed, cannot participate in the study

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, 6200 MD, Netherlands

Location

Related Publications (1)

• Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia. 2020 Jun;63(6):1211-1222. doi: 10.1007/s00125-020-05128-1. Epub 2020 Mar 17.

  PMID: 32185462 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Patrick Schrauwen, Ph.D.

  Maastricht University Medical Center (MUMC)

  STUDY DIRECTOR

• Lena Bilet, MSc.

  Maastricht University Medical Center (MUMC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD student

Study Record Dates

• First Submitted: April 10, 2012
• First Posted: April 12, 2012
• Study Start: April 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

NL (1)