The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 207
- 试验地点
- 2
- 主要终点
- Mean adipocyte size (µm2) assessed using Image J software.
研究概览
简要总结
Obesity is a major risk factor for Type 2 diabetes. However, two obese people of the same height and weight can have very different risks of the condition. As a greater proportion of the population is becoming obese, scientists need to understand more about why some people develop Type 2 diabetes at lower weight and why some people stay healthy despite being obese. The investigators and others provided evidence for genetic factors associated with higher weight for a given height but lower risk of diabetes, lower cholesterol and fat levels, lower blood pressure and lower risk of heart disease. The investigators showed that people who carry these genetic factors are able to store extra fat in a safe place, which is under the skin, as they gain weight. The proposed project aims to establish whether or not these genetic factors are associated with better development and function of fat tissue in storing extra fat. It is thought that a healthy and functional fat tissue in the human body has a key role in modifying the risk of diseases such as Type 2 diabetes, heart disease and hypertension.
Volunteers from Exeter 10,000 who gave their permission to contact them about further research will be recruited to the study. In those that agree, detailed body size measures, including body composition assessments by the BodPodTM machine will be recorded, a blood sample will be collected, and a small subcutaneous abdominal fat biopsy will be collected to measure fat cell size and from which a sample will be stored for future analyses. The results between people with and without the particular genetic changes of interest will be compared.
Knowing more about these genetic changes and how fat cells work could help to improve understanding of the factors that predispose, delay or protect obese individuals from Type 2 diabetes and other metabolic disturbances.
详细描述
Introduction:
Diabetes is the most common chronic metabolic disease and is a major source of morbidity and mortality. It is one of the biggest healthcare challenges facing the United Kingdom's (UK) National Health Service (NHS) with more than 2.6 million adults diagnosed in the UK, with the vast majority (90%) having Type 2 diabetes (T2D). It is anticipated that the numbers will continue to rise, in part due to the increasing levels of obesity in the population.
Type 2 diabetes is characterised by high blood glucose levels in the context of increasing insulin resistance and reduced beta cell function, and this can develop over several years with individuals unaware of the problem.
Research groups in Exeter are leading efforts to identify the genetic factors that influence why some people develop Type 2 diabetes despite relative leanness, whilst many obese people do not get the disease. The investigators have identified many such factors but now wish to study them in more detail to understand the role of a healthy and functioning adipose tissue in the disease mechanism. This study builds on a previous 'recruit by genotype' study to explore the size of fat cells in people carrying the most genetic factors for being fatter but healthier (fATDIVA (for Adipose Tissue DIabetes VAriants) NCT02505321). The investigators will expand on the range of genetic variations to be undertaken in the research volunteers. The preliminary data from fATDIVA helped to secure prestigious funding from Diabetes UK to expand this work to improve understanding of the complex processes that lead to Type 2 diabetes.
The investigators are trying to understand how genetic variations cause differences in the human ability to store fat. The hypothesis to be tested is that individuals carrying different genetic variations have different abilities to store fat under the skin as subcutaneous fat tissue. This could lead to an improved understanding of subcutaneous fat storage. It is very unlikely that scientists will be able to reverse substantially the rising numbers of people becoming overweight or obese as they age, therefore this study's findings could be important in identifying how to reduce the risk of disease caused by obesity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Demographics: Age 18-75 inclusive
- •Ethnicity: Reflective of local demographic
- •Mental capacity: Willing and able to provide informed consent
排除标准
- •Medical history: History of bariatric surgery and recent significant weight loss/gain (+/- 3 kgs/ half a stone in the last 3 months); connective tissue disease, pregnancy and lactation (if women are recruited).
- •Medications: Currently prescribed oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
- •Mental capacity: Unable/unwilling to provide informed consent.
结局指标
主要结局
Mean adipocyte size (µm2) assessed using Image J software.
时间窗: Within 12 months of recruitment date of final participant
ImageJ is a cross-platform image analysis tool developed to measure particle/cell size and will be used here to measure adipocyte size to test whether or not individuals carrying a high genetic load of "favourable adiposity" alleles have smaller subcutaneous fat cells.
次要结局
- Adipose tissue expression of genes that are markers of adipogenesis (PPARy, CREBP).(Within 12 months of recruitment date of final participant)
- Adipose tissue expression of genes that are determinants of adipose inflammation (IL-1beta, IL-6, and 8, TNFalpha, MCP-1/CCL2).(Within 12 months of recruitment date of final participant)
- Adipose tissue expression of genes that are markers of fibrosis (SPARC, collagens, TGFbeta, LOX).(Within 12 months of recruitment date of final participant)