Defining Adipose Tissue Lipid Deposition in Normal Weight Individuals With a Genetic Predisposition to Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- Level of Circulatory Lipids following Triglyceride stimulation test (OTTT) (mmol/L)
研究概览
简要总结
The adipose (fat) cells under the skin are where individuals store excess fat. The more excess fat they have, the more "strain" they put on these cells which then get bigger and don't work as well as they should. Having some fat under the skin is important. People who have a genetic defect which results in them having almost no fat under their skin have a very high risk of a condition called insulin resistance (where the body does not respond as well to insulin and blood sugar levels rise). This can lead to diabetes and heart disease despite them not being overweight.
Scientists have only recently started to understand the importance of fat in insulin resistance and how people unable to store fat very well can have insulin resistance despite not being obese. The investigators have also recently discovered that small changes in a person's genetic code (their body's instruction manual) may also affect their ability to store fat and would like to explore this in more detail. To do this, they will recruit volunteers from the Exeter 10,000 study who gave permission to contact them about further research. The investigators will collect detailed body size measures and blood samples taken before and after a special drink that is high in fat (similar to a thick milk shake), then compare the results between people with and without the particular genetic changes of interest.
Knowing more about these genetic changes and how fat cells work could help to improve understanding about why some people develop diabetes and heart disease despite a relatively normal BMI.
详细描述
Hypothesis:
Individuals carrying different genetic variations have different abilities to store fat under the skin.
Aim: To improve understanding of "adipose tissue dysfunction" using human genetics, and demonstrate that lipid uptake into fat cells is compromised in subjects with 'polygenetic lipodystrophy' alleles.
Objectives:
- Identify individuals with genetic risk variants of interest and controls matched for gender, age and BMI.
- Undertake detailed physiological assessments including an Oral Triglyceride Tolerance Test (OTTT) (blood samples before and after a fatty drink), detailed body size measures and an optional fat biopsy.
- Using the samples collected, test whether or not individuals carrying a high genetic load of "polygenic lipodystrophy" alleles:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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: Treated Diabetes (including insulin and GLP-1 analogues), 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.
- •Medications: Currently prescribed glucose-lowering medication (we will NOT exclude those controlling their diabetes with diet alone), oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
- •Mental capacity: Unable/unwilling to provide informed consent.
研究组 & 干预措施
fATDIVA - OTTT (Cases)
Individuals identified with the "polygenic lipodystrophy" genetic variants of interest will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.
干预措施: Oral Triglyceride Tolerance Test (OTTT) (Other)
fATDIVA - OTTT (Cases)
Individuals identified with the "polygenic lipodystrophy" genetic variants of interest will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.
干预措施: Abdominal fat biopsy (optional) (Procedure)
fATDIVA - OTTT (Controls)
Control individuals carrying the average number of risk alleles and matched to individuals identified with the "polygenic lipodystrophy" genetic variants of interest for gender, age and BMI, will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.
干预措施: Oral Triglyceride Tolerance Test (OTTT) (Other)
fATDIVA - OTTT (Controls)
Control individuals carrying the average number of risk alleles and matched to individuals identified with the "polygenic lipodystrophy" genetic variants of interest for gender, age and BMI, will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.
干预措施: Abdominal fat biopsy (optional) (Procedure)
结局指标
主要结局
Level of Circulatory Lipids following Triglyceride stimulation test (OTTT) (mmol/L)
时间窗: Within 12 months of recruitment date of final participant
Level of Circulatory Lipids will be assessed using measures of triglyceride levels from each post-prandial time point sample.
次要结局
- Mean adipocyte size assessed using Image J(Within 12 months of recruitment date of final participant)
- Incremental Area under the Curve NEFA levels (µmol/L)(Within 12 months of recruitment date of final participant)