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

27 de fevereiro de 2016 atualizado por: 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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

81

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Holanda
    • Limburg
      • Maastricht, Limburg, Holanda, 6200MD
        • Maastricht University

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

40 anos a 70 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Macho

Descrição

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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Comportamental: 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.
Experimental: 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
Comportamental: 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.
Experimental: Type 2 diabetes patients
This group will exist of patients that suffer from type 2 diabetes
Comportamental: 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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Proton Magnetic resonance spectroscopy to measure the reduction in liver fat content after a training intervention
Prazo: 16 weeks
16 weeks
Magnetic resonance spectroscopy to measure the ATP and Pi concentrations in the liver
Prazo: 16 weeks
16 weeks
13C-methionine breath test to measure hepatic mitochondrial function
Prazo: 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
Prazo: 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
Prazo: 16 weeks
16 weeks

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Peripheral arterial tonometry to measure endothelial function, as a marker for cardiovascular risk.
Prazo: 16 weeks
16 weeks
Echography of the heart to measure diastolic dysfunction
Prazo: 16 weeks
16 weeks
Fat biopsy to measure adipose tissue inflammatory markers and adipocyte size before and after training intervention
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Bram Brouwers

Colaboradores

Dutch Diabetes Research Foundation

Investigadores

  • Diretor de estudo: Patrick Schrauwen, PhD, Maastricht University
  • Investigador principal: Bram MW Brouwers, M.S., Maastricht University

Publicações e links úteis

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Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de março de 2011

Conclusão Primária (Real)

1 de novembro de 2015

Conclusão do estudo (Real)

1 de novembro de 2015

Datas de inscrição no estudo

Enviado pela primeira vez

16 de março de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

16 de março de 2011

Primeira postagem (Estimativa)

17 de março de 2011

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

1 de março de 2016

Última atualização enviada que atendeu aos critérios de controle de qualidade

27 de fevereiro de 2016

Última verificação

1 de fevereiro de 2016

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • MEC 11-3-002

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