Epigenetics of Muscle Insulin Resistance
11 de outubro de 2019 atualizado por: Dawn K Coletta, University of Arizona
Epigenetics and the Origin of Muscle Insulin Resistance in Humans Aims 1-3
The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues.
DNA methylation is a normal chemical process in the body that modifies DNA.
By studying this, the investigators hope to better understand the causes of insulin resistance.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
Insulin resistance is defined as the decreased ability of insulin to perform its biological function in the muscle, liver and fat.
Genetic and environmental factors are known to influence insulin sensitivity.
It is not known how this is mediated.
This study looks at the role of epigenetics (modifications of proteins associated with DNA and methylation of DNA) in alterations in insulin resistance.
The investigators will study lean healthy people, obese non-diabetic people and people with type 2 diabetes to characterize the DNA methylation patterns in muscle in each group.
The second aim of the study is to see how a single bout of exercise affects the DNA methylation in the muscle.
The third aim looks at the effect of 8 weeks of supervised exercise on the DNA methylation.
Tipo de estudo
Observacional
Inscrição (Real)
72
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
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Arizona
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Tucson, Arizona, Estados Unidos, 85724
- University of Arizona
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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
21 anos a 55 anos (Adulto)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Método de amostragem
Amostra Não Probabilística
População do estudo
Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2) obese volunteers without type 2 diabetes, and 3) volunteers with type 2 diabetes
Descrição
Inclusion Criteria
- Age 21-55
- BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30- 50; type 2 diabetic, BMI between 30- 50.
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- Subjects must range in age as described in each specific protocol.
Subjects must have the following laboratory values:
- Hematocrit ≥ 35 vol%
- Serum creatinine ≤ 1.6 mg/dl
- AST (SGOT) < 2 times upper limit of normal
- ALT (SGPT) < 2 times upper limit of normal
- Alkaline phosphatase < 2 times upper limit of normal
- Triglycerides < 150 mg/dl for nondiabetics
- Triglycerides <300 for diabetics
- INR ≤ 1.3
Exclusion Criteria
- Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin secretion.
- Subjects receiving Gemfibrozil must not also be receiving a statin.
- Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
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
Coortes e Intervenções
Grupo / Coorte |
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Aim 1
This experiment will use the next generation sequencing reduced representation bisulfite sequencing to define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers.
The investigators will test the hypotheses that: (a) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (b) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (c) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.
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Aim 2
This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that: (a) Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and (b) Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.
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Aim 3
This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that: (a) There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes, (b) There is altered methylation of genes involved in inflammation and cytoskeletal structure.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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DNA methylation of genes in insulin resistance
Prazo: 9 months
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DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.
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9 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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mRNA expression of genes
Prazo: 9 months
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mRNA expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeletal signaling are altered in insulin resistance, with an acute episode of exercise and with 8 weeks of exercise training.
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9 months
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Dawn K Coletta, Ph.D., University of Arizona
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 (Real)
1 de novembro de 2016
Conclusão Primária (Real)
2 de novembro de 2018
Conclusão do estudo (Real)
2 de novembro de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
21 de agosto de 2017
Enviado pela primeira vez que atendeu aos critérios de CQ
23 de agosto de 2017
Primeira postagem (Real)
24 de agosto de 2017
Atualizações de registro de estudo
Última Atualização Postada (Real)
14 de outubro de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
11 de outubro de 2019
Última verificação
1 de outubro de 2019
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 1612045470
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Não
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
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