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Optimizing the Beneficial Health Effects of Exercise for Diabetes: Focus on the Liver!

27 février 2016 mis à jour par: Bram Brouwers

Due to the western lifestyle, correlated with a high calorie intake and low physical activity, obesity is becoming a major health problem. All over the world obesity reaches epidemic proportions. Obesity is closely linked to type 2 diabetes, a multi-factorial disease that increases the presence of multiple health problems. Until now, exercise and dietary intervention seem to be the single most effective interventions to treat obesity and type 2 diabetes mellitus. In obesity and type 2 diabetes, not only fat accumulation in adipose tissue, but also fat accumulation in the peripheral tissues occurs. Fat accumulation in peripheral tissues has been associated with insulin resistance. Exercise seems to have a positive effect on the accumulation of fat in the peripheral tissue and on the insulin sensitivity in type 2 diabetic patients.

In this study we want to investigate if a prolonged exercise training program can lower the intrahepatic lipid content and can improve the metabolism of the liver in type 2 diabetic patients and patients with non-alcoholic fatty liver disease, and to examine if this leads to improvements in metabolic risk markers. To this end, we will include investigation of the effect of exercise on adipose tissue (inflammatory markers and adipocyte size) and skeletal muscle (ex vivo lipid metabolism) to incorporate the effect of exercise on liver, muscle and adipose tissue and to clarify the crosstalk between these tissues in the pathophysiology of type 2 diabetes.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

81

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Pays-Bas
    • Limburg
      • Maastricht, Limburg, Pays-Bas, 6200MD
        • Maastricht University

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

40 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Homme

La description

Inclusion Criteria:

  1. All subjects:

    • Male sex
    • Age 40-70 years
    • BMI 27-35 kg/m2
    • Stable dietary habits
    • Sedentary: No participation in any kind of sports for at least 2 years.

  2. For diabetic patients only:

    • Must be on sulphonylurea or metformin therapy for at least 6 months with constant dose for at least 2 months, or on a dietary treatment for at least 6 months
    • Well-controlled diabetes: fasting plasma glucose concentration ≥ 7.0 mmol/l and < 10.0 mmol/l at the time of screening.

  3. For subjects with non-alcoholic fatty liver disease:

    • Liver fat content ≥ 5,56%, based on the formula of Kotronen et al. and confirmed with MRS.
    • Fasting plasma glucose concentration must be < 7.0 mmol/l

  4. For control subjects:

    • Liver fat content < 5,56%, based on the formula of Kotronen et al. and confirmed with MRS.
    • Normoglycemic according to the WHO criteria (OGTT)

Exclusion Criteria:

  1. All subjects:

    • Female sex
    • Unstable body weight (weight gain or loss > 3 kg in the past three months)
    • Participation in an intensive weight-loss program or in vigorous exercise program during the last year before the start of the study.
    • Active cardiovascular disease. (This will be determined by questionnaires and by screening on medication. Furthermore, all subjects will undergo a physical examination by a medical doctor).
    • Chronic renal dysfunction (creatinine > 2 increased (normal values: 64-104 µmol/l))
    • Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
    • Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg
    • Haemoglobin < 7.5 mmol/l (anaemia)
    • Blood donor
    • Use of medication known to interfere with glucose homeostasis (i.e. corticosteroids), except for diabetic patients.
    • Use of anti-thrombotic medication
    • Claustrophobia and contra-indications for MRI
    • Abuse of alcohol(> 3 units (1unit = 10 gram ethanol) per day)
    • Abuse of drugs
    • Participation in another biomedical study within 1 month before the first screening visit

  2. For diabetics:

    • Severe diabetes which requires application of insulin or patients with diabetes-related complications

  3. For controls:

    • Liver disease or liver dysfunction (ALAT > 2.5 x increased)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Healthy control
This group will exist of healthy obese that are matched for BMI and age with the type 2 diabetes group and non-alcoholic fatty liver disease group.
Comportemental: Exercise intervention
Subjects will be training for 12 week, 3 times a week. Two times a week they will perform a 30 minutes bicycle training. Once a week they will perform a 30 minutes resistance training.
Expérimental: Non-alcoholic fatty liver disease
This group will exist of people that suffer from non-alcoholic fatty liver disease. They will be matched for BMI and age according to the Type 2 diabetes group
Comportemental: Exercise intervention
Subjects will be training for 12 week, 3 times a week. Two times a week they will perform a 30 minutes bicycle training. Once a week they will perform a 30 minutes resistance training.
Expérimental: Type 2 diabetes patients
This group will exist of patients that suffer from type 2 diabetes
Comportemental: Exercise intervention
Subjects will be training for 12 week, 3 times a week. Two times a week they will perform a 30 minutes bicycle training. Once a week they will perform a 30 minutes resistance training.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Proton Magnetic resonance spectroscopy to measure the reduction in liver fat content after a training intervention
Délai: 16 weeks
16 weeks
Magnetic resonance spectroscopy to measure the ATP and Pi concentrations in the liver
Délai: 16 weeks
16 weeks
13C-methionine breath test to measure hepatic mitochondrial function
Délai: 16 weeks
Subjects will drink a solution of 200ml H2O with 13C-Methionine. The following 2 hours, every 10 minutes a breath sample will be taken and analysed to measure the concentration of 13C in the exhaled breath.
16 weeks
Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility
Délai: 16 weeks
After taking fasting blood samples, a primed constant infusion of glucose is initiated. Plasma glucose levels are clamped at ~5 mmol/L by variable co-infusion of 20 % glucose. Every 5 minutes, blood is sampled for immediate determination of plasma glucose concentration. Glucose infusion rate is adjusted to obtain plasma glucose levels of ~5 mmol/L (euglycemia). A bolus of insulin is then infused. Before and during steady state, substrate oxidation is measured using an indirect calorimeter, which determines metabolic flexibility.
16 weeks
Blood sampling to determine the concentration of cardiovascular risk factors in the blood before and after exercise
Délai: 16 weeks
16 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Peripheral arterial tonometry to measure endothelial function, as a marker for cardiovascular risk.
Délai: 16 weeks
16 weeks
Echography of the heart to measure diastolic dysfunction
Délai: 16 weeks
16 weeks
Fat biopsy to measure adipose tissue inflammatory markers and adipocyte size before and after training intervention
Délai: 16 weeks
A small amount of abdominal subcutaneous adipose tissue (~1g) will be collected under local anaesthesia (2% lidocain) using needle biopsy (with the needle connected to a vacuum syringe). Inflammatory markers in the adipose tissue (e.g. IL-6, IL-8, IL-1b, PAI-1, TNFa, CD68, CD163, CD11b, MCP-1, leptin, adiponectin mRNA expression) and adipocyte size will be analysed
16 weeks
Muscle biopsy to measure muscle mitochondrial density, muscle mitochondrial function and muscle lipid metabolism
Délai: 16 weeks
. After local anaesthesia (2.0% Xylocain without adrenaline), a 5-mm diameter side-cutting needle will be passed through a 7-mm skin incision, according to the protocol of the Medical Ethical committee of the Academic Hospital and University of Maastricht. The muscle biopsy will be used to measure ex vivo lipid metabolism, muscle mitochondrial density and muscle mitochondrial function.
16 weeks

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Bram Brouwers

Collaborateurs

Dutch Diabetes Research Foundation

Les enquêteurs

  • Directeur d'études: Patrick Schrauwen, PhD, Maastricht University
  • Chercheur principal: Bram MW Brouwers, M.S., Maastricht University

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2011

Achèvement primaire (Réel)

1 novembre 2015

Achèvement de l'étude (Réel)

1 novembre 2015

Dates d'inscription aux études

Première soumission

16 mars 2011

Première soumission répondant aux critères de contrôle qualité

16 mars 2011

Première publication (Estimation)

17 mars 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

1 mars 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

27 février 2016

Dernière vérification

1 février 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MEC 11-3-002

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