Understanding the mechanistic links between nutrition, skeletal muscle and exercise and type 2 diabetic phenotypes in older Indians.

了解老年印度人的营养、骨骼肌和运动与 2 型糖尿病表型之间的机制联系。

• 批准号: MR/T00861X/1
• 负责人: Stephen Harridge
• 金额: $ 4.98万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT00861X%2F1
• 关键词: Understanding; mechanistic; links; between; nutrition

Diabetes is a global epidemic posing immense public health challenges across the world, but particularly in the growing populations of the Indian sub-continent. In India alone the number of people with this disease is over 65 million the annual cost of this disease is now enormous. It is thus already a major health and health-care issue and one which is continuing to grow with the changing demographic towards that of an older population. It is in the older population where the biggest changes and challenges are occurring. Type 2 diabetes is a metabolic disease typically characterized by insulin resistance and caused primarily by a combination of high energy intake and low energy expenditure. Thus individuals typically are overweight (have a high body mass index) and have low levels of physical activity. In Indians's there is a second population of individuals who have a similar metabolic condition, but are not overweight - termed "metabolically obese". Here, there appears to be fat accumulation in areas not typically associated with adipose deposition. One of these areas is in skeletal muscle. Muscle plays a vital role in metabolic health. It is the biggest store and biggest user of glucose in the body, providing a clear link to physical inactivity. This project seeks to increase our understanding of the mechanisms underpinning these two different types of diabetes in India.It will do this by identifying the the skeletal muscle metabolic /lipid characteristics of Indians over 55 years who represent the two different metabolic phenotypes (as well as healthy controls) and how this is related to beta cell function and insulin sensitivity, body composition, cardio-respiratory fitness and muscle function. It will compare the metabolic (metabolomic) and mitochondrial phenotype (respiratory function, proteome, transcriptome) in skeletal muscle in terms of Indians exhibiting the two different metabolic types. It will seek to establish differences in lipid accumulation and cellular phenotypes in muscle-derived cells (myoblasts and fibroblasts) studied in culture (outside the body) obtained from the two different diabetic phenotypes and determine if this relates to altered mitochondrial function. It will then compare the above with similar measures made on 2nd/3rd generation Indians living in the UK. Finally, the project will undertake a longitudinal to investigate the effects of an intervention programme, which uses targeted nutritional supplementation combined with both aerobic and strength training exercise to improve mitochondrial, muscle size and metabolic health in the different Indian diabetic phenotypes described above.

糖尿病是一种全球流行病，在世界各地构成巨大的公共卫生挑战，特别是在印度次大陆不断增长的人口中。仅在印度，患有这种疾病的人数就超过6500万，每年的费用是巨大的。因此，这已经是一个重大的健康和保健问题，而且随着人口结构向老年人转变，这一问题还在继续增加。在老年人口中，正在发生最大的变化和挑战。2型糖尿病是一种代谢性疾病，通常以胰岛素抵抗为特征，主要由高能量摄入和低能量消耗的组合引起。因此，个体通常超重（具有高身体质量指数）并且具有低水平的身体活动。在印度人中，还有第二种人群，他们有类似的代谢状况，但不超重-被称为“代谢性肥胖”。在这里，似乎有脂肪堆积的地区通常不与脂肪沉积。其中一个区域是骨骼肌。肌肉在代谢健康中起着至关重要的作用。它是体内最大的葡萄糖储存和最大的葡萄糖使用者，与身体不活动有着明确的联系。该项目旨在增加我们对印度这两种不同类型糖尿病的基础机制的理解。它将通过识别代表两种不同代谢表型的55岁以上印度人的骨骼肌代谢/脂质特征来实现这一目标（以及健康对照）以及这与β细胞功能和胰岛素敏感性，身体成分，心肺功能和肌肉功能。它将比较代谢（代谢组学）和线粒体表型（呼吸功能，蛋白质组，转录组）在骨骼肌中的印第安人表现出两种不同的代谢类型。它将寻求建立在从两种不同的糖尿病表型获得的培养物（体外）中研究的肌肉来源的细胞（成肌细胞和成纤维细胞）中脂质积累和细胞表型的差异，并确定这是否与线粒体功能改变有关。然后，将上述措施与对生活在英国的第二代/第三代印度人采取的类似措施进行比较。最后，该项目将进行纵向调查，以研究干预方案的效果，该方案使用有针对性的营养补充剂，结合有氧和力量训练运动，以改善上述不同印度糖尿病表型的线粒体，肌肉大小和代谢健康。