The Effect of Lowered Physical Activity on Insulin Sensitivity and Lipid and Glucose Metabolism
27 de mayo de 2015 actualizado por: Lena Bilet, Maastricht University Medical Center
The Effect of Lowered Physical Activity (Induced by Lower Limb Suspension (ULLS)) on Insulin Sensitivity and Lipid and Glucose Metabolism
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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
In the Netherlands and worldwide, the number of individuals suffering from obesity and type 2 diabetes mellitus is rising steadily.
It is well established that obesity predisposes individuals to accumulation of excessive fat in non-adipose tissues such as the liver, the heart and skeletal muscle (called steatosis or ectopic fat accumulation).
Furthermore, in sedentary humans ectopic fat accumulation in skeletal muscle is strongly associated with insulin resistance.
However, paradoxically, IntraMyoCellular Lipid (IMCL) content is also increased in highly insulin sensitive endurance trained subjects (known as the athlete's paradox).
This is suggesting that IMCL per se is not causative in skeletal muscle insulin resistance.
The increased IMCL storage following endurance training serves to match training-induced increase in oxidative capacity and reliance on fat as a substrate during exercise, whereas in obesogenic/diabetogenic conditions the high fat availability is not matched by improved oxidative capacity.
It is therefore speculated that under the latter conditions, the lipid intermediates of IMCL metabolism such as diacylglycerol (DAG), ceramides and fatty acyl-CoAs will accumulate and impede cellular insulin signalling.
The rate of oxidative capacity is regulated by mitochondria, which are cellular organelles responsible for cellular energy production and cellular metabolism.
Therefore, the overall hypothesis of this project is that a low muscle mitochondrial oxidative capacity can lead to muscle fat accumulation and/or accumulation of lipid intermediates when fatty acid availability is high, and this may result in insulin resistance in skeletal muscle.
Tipo de estudio
Intervencionista
Inscripción (Actual)
13
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Maastricht, Países Bajos, 6200 MD
- Maastricht University Medical Center
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 35 años (Adulto)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Masculino
Descripción
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: unilateral lower limb suspension
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.
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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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Insulin sensitivity
Periodo de tiempo: after 9 days of ULLS
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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.
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after 9 days of ULLS
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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intramyocellularlipid content
Periodo de tiempo: after 9 days of ULLS
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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.
Muscle tissue will immediately be frozen and stored for later determination of Intramyocellular lipid content.
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after 9 days of ULLS
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Lipid intermediates
Periodo de tiempo: after 9 days of ULLS
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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.
Lipid intermediates will further be investigated from the skeletal muscle tissue ex vivo.
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after 9 days of ULLS
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Lipid metabolism
Periodo de tiempo: after 9 days of ULLS
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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.
Lipid metabolism will further be investigated from the skeletal muscle tissue ex vivo.
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after 9 days of ULLS
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Glucose metabolism
Periodo de tiempo: after 9 days of ULLS
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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.
Glucose metabolism will further be investigated from the skeletal muscle tissue ex vivo.
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after 9 days of ULLS
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Patrick Schrauwen, Ph.D., Maastricht University Medical Center (MUMC)
- Investigador principal: Lena Bilet, MSc., Maastricht University Medical Center (MUMC)
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de abril de 2012
Finalización primaria (Actual)
1 de agosto de 2013
Finalización del estudio (Actual)
1 de agosto de 2013
Fechas de registro del estudio
Enviado por primera vez
10 de abril de 2012
Primero enviado que cumplió con los criterios de control de calidad
10 de abril de 2012
Publicado por primera vez (Estimar)
12 de abril de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
28 de mayo de 2015
Última actualización enviada que cumplió con los criterios de control de calidad
27 de mayo de 2015
Última verificación
1 de mayo de 2015
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- NL38795.068.11/METC 11-3-074
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