Investigating the Metabolic and Lipidomic Profiles That Are Associated With Varying Grades of Diabetic Maculopathy and Retinopathy in South Wales
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Analysis of serum lipidome of people with differing severity of DR
研究概览
简要总结
Diabetes mellitus is a disorder of sugar and fat metabolism which results in damage to the small blood vessels in various organs, this includes the retina - the part of the eye that processes light into a nerve impulse. This leads to damage and blindness via various different mechanisms that are not fully understood.
In this study the objective is to recruit people with diabetes and various stages of diabetic eye disease and measure a large number of different chemicals within the blood that might be associated with damage and dysfunction within the retina. Additionally, it will examine the different bacteria within the gut that might affect disease in the eye via chemicals circulating in the blood. This will require participants to have blood samples taken and to provide urine samples. The blood will be analysed with specialised instruments to identify specific molecules circulating within the blood. Participants will also need to allow researchers to look at their medical records, previous photographs and specialist scans of the back of the eye to grade their diabetic retinopathy. This will allow us to identify potential ways in which these could be targeted for future benefit for people with diabetes to hopefully prevent deterioration of their vision.
详细描述
Introduction
Diabetic Retinopathy (DR) places a huge burden on ophthalmic clinical services throughout the world as one of the leading causes of reduced vision in working age adults [1,2]. This is only going to worsen as the population grows with estimates of 700 million patients worldwide by 2045, with increase in people with DR from an estimated 103 million in 2020 to 160 million in 2045 [3]. The pathophysiology of DR is poorly characterised, and although the investigators understand some aspects of the disease process, some remain unexplored.
Early in the development of DR there is a breakdown of the blood-retinal barrier with loss of pericytes. This allows for leakage of vascular constituents in the retina and also flow of metabolic markers from retinal tissue into the systemic circulation[4]. There are a number of aspects of this process that warrant further investigation from a perspective of the metabolic disturbances that occur, and what might be driving them.
Early in the development of DR there is disruption to the autoregulation of blood flow to the retina with an apparent disturbance in arginine metabolism as reflected in serum metabolomic analysis [5,6]. This evidence and evidence of subsequent alterations in fatty acid oxidation as well as complex lipid synthesis is derived from animal models and small population studies in very specific ethnic cohorts, such as the Pima Indians in the USA [5,7]. Furthermore, there appears to be limited evidence for an effect on purine metabolism which is crucial for phosphocholine and phosphatidylethanolamine synthesis [8].
Along with disruption in synthesis of these crucial lipids, ceramide metabolism is disturbed with a reduction in the "probarrier", very long chain ceramides and increased production of shorter chain "pro-apoptotic" ceramides [9-12]. This provides a link to the potential therapeutic benefit of fenofibrate which has been shown in large scale studies to have a beneficial effect on DR independent of its effects on serum Low Density Lipoprotein (LDL) levels [9,13]. This is postulated to potentially be due to altered ceramide metabolism and synthesis, a process that is well established to be disrupted in people with diabetes [14].
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 2 diabetes mellitus
- •Male or female aged 18 - 80 inclusive
排除标准
- •Participant unable or unwilling to consent to inclusion in the study
- •Prior treatment with intravitreal therapies for DMO
- •Potential participant with a known infective disease that may put the study team at risk (eg. TB, HIV, hepatitis)
- •Age 17 yo or less or 81 yo or older
- •Known underlying genetic condition affecting lipid metabolism
结局指标
主要结局
Analysis of serum lipidome of people with differing severity of DR
时间窗: 5 years
To investigate the serum lipidome in people with differing severity of DR
次要结局
- Metabolic pathway analysis with reference to diabetic maculopathy(5 years)
- Metabolic pathway analysis with additional analysis of interaction with microbiome(5 years)
- Metabolic pathway analysis with reference to altered lipid metabolism(5 years)
研究者
Frank Sanders
Honorary Research Fellow
Hywel Dda Health Board