Genetic and Epigenetic Contribution to Increased Risk of T2D in the UAE
试验速览
- 阶段
- 不适用
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Total physical activity levels through 7 days among Emiratis with or without T2D.
研究概览
简要总结
T2D is a global public health crisis and a threat to socioeconomic development of all nations, particularly in developing countries. Countries in the Gulf region, including the UAE, have some of the highest rates of T2D worldwide. The epidemic in the region has grown in parallel with the worldwide rise in obesity, which is fuelled by rapid urbanization, nutrition transition, and increasing sedentary lifestyles. Whether these unfavourable changes in environmental risk factors can explain the increased risk of T2D in the region, or whether the populations in the Gulf region are more genetically susceptible to disease is yet to be investigated.
In this study, for the first time, the contribution of environmental, genetic, and epigenetic factors towards the increased risk of T2D amongst the population of the UAE will be investigated. This will be through, firstly, identifying environmental risk factors with higher prevalence rates, and bigger effect sizes on T2D in the UAE in comparison to Europe. Secondly, identifying genetic variants known to predict T2D in Europeans/other populations, but with stronger association with T2D in Emiratis. Thirdly, identifying novel genetic variants that are perhaps rare in Europeans/other populations, but confer increased risk for T2D in the UAE. Lastly, candidate genes underlying T2D pathogenesis via epigenetic mechanisms will be identified in Emiratis and Europeans. The end result is to identify the underlying candidate markers and mechanisms involved in T2D pathogenesis, which can better explain differences in magnitude of risk across populations.
详细描述
The general aim of my research will be to investigate the contribution of environmental, genetic, and epigenetic factors to the increased risk of T2D in the Emirati population compared to Europeans. My specific aims will include:
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Establish a cohort of Emirati T2D cases and controls to enable investigation of genetic and environmental risk factors for T2D in the UAE.
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Use the data collected to examine the contribution of adiposity, physical inactivity, and dietary habits to the increased risk of T2D amongst the Emiratis compared to the Europeans living in the UK.
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Investigate whether known and novel genetic variants account for the high risk of T2D in Emiratis.
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Investigate DNA methylation profiles of subjects with T2D and non-diabetic controls in Emiratis and Europeans, and identify the differences in methylation profiles between the two populations.
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Identify candidate methylation regions that are associated with, and could account for the higher risk of T2D amongst Emiratis.
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ESTABLISH A COHORT OF EMIRATI T2D CASES AND CONTROLS TO ENABLE INVESTIGATION OF GENETIC AND ENVIRONMENTAL FACTORS FOR T2D IN THE UAE.
STUDY DESIGN: Case-control study SUBJECTS: 600 Emirati adults with T2D, and 600 age-sex matched control free from T2D, recruited from Imperial College London Diabetes Centre (ICLDC) based in Abu Dhabi, UAE. Recruitment started in April 2016. Participants include men and women ≥18 years old. They are provided with a complete information letter about the study, and are asked to sign a written consent to be included in the study.
METHODS: Participants will undergo health examination, which will be conducted by nurses and interviewers at the ICLDC. Examinations will include a brief medical history, anthropometric measures including weight, height, waist and hip circumferences, and blood pressure. Blood samples will be collected after an 8-hour fast for biochemical analysis, which includes measuring glucose, insulin, HDL and total cholesterol, and triglycerides levels. Diabetes will be defined using 1999 WHO criteria. Obesity will be assessed by BMI, where subjects will be classified as obese if BMI ≥30 kg/m2 and overweight if 25 kg/m2 ≤ BMI < 30 kg/m2. Additionally, participants will be asked to fill a physical activity questionnaire to assess their activity at work, transport, and recreational times during a typical week. A subset of 200 participants, 100 free from T2D and 100 with T2D, will be asked to wear Actigraph activity monitors that will measure their physical activity levels for 7 days. These participants will also be asked to fill out a food frequency questionnaire to assess their dietary habits.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fasted for at least 8 hrs
- •Arab-Emiati ethnicity
- •Males and Females
- •Diagnosed with prediabetes OR
- •Diagnosed with type 2 diabetes OR
- •Have normal glucose tolerance
排除标准
- •Other types of diabetes
- •Undergone a recent surgical operation that hinders them from carrying out their normal day to day chores
结局指标
主要结局
Total physical activity levels through 7 days among Emiratis with or without T2D.
时间窗: 2018-2020
Physical activity levels during a week including 5 working days and 2 weekend days collected using Actigraph GT9X accelerometer. Minutes per day of moderate to vigorous physical activity (MVPA) based on accelerometry calculated in ActiLife software.
Association of low physical activity (LPA) with risk of T2D in Emiratis
时间窗: 2018-2020
Association between LPA and T2D statistically determined with logistic regression analysis by odds ratio (OR). The OR of having LPA and T2D versus having MPA or HPA and T2D.
Physical activity levels at work, transport and leisure time in a typical day among Emiratis with or without T2D.
时间窗: 2017-2019
Reported physical activity in a typical week collected using the Global Physical Activity Questionnaire (GPAQ).The GPAQ comprises of 16 items that quantify the physical activity levels of a normal week for an individual. It was developed to estimate the total weekly volume of moderate-to-vigorous physical activity (MVPA) in a typical week among three domains; work, transportation, and recreational/leisure activities. Based on the GPAQ guidelines, calculated total activity score is classified into three categories, overall low- (LPA), moderate- (MPA), or high- (HPA) physical activity.
Association of obesity with risk of T2D among Emiratis
时间窗: 2017-2019
Body mass index (BMI) calculated as weight in kilograms divided by the square of height in meters (Kg/m2), and classified as normal ( \< 24kg/m2), overweight (25 - 29kg/m2), and obese ( ≥ 30kg/m2). Association between BMI and T2D statistically determined with logistic regression analysis by odds ratio (OR). OR will define the increased risk of T2D with a unit increase in BMI (1kg/m2).
Genetic risk variants associated with increased risk of T2D in Emiratis
时间窗: 2020-2021
Global screening array will be used to genotype \>500,000 Single Nucleotide Polymorphisms (SNPs) from DNA samples extracted from whole blood samples , which are collected at the inclusion visit from participants with or without T2D. Association between evaluated genetic variants (SNPs) and T2D statistically determined if the p-value is found to be close to or lower than the Genome-wide significance threshold (p \<5\*10-8).
次要结局
未报告次要终点