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

糖尿病是一种全球流行病，在世界各地构成了巨大的公共卫生挑战，特别是在印度次大陆日益增长的人口中。仅在印度，这种疾病的患病人数就超过6500万人，这种疾病的年成本现在是巨大的。因此，这已经是一个主要的保健和保健问题，而且随着人口结构的变化向老年人口的转变，这个问题还在继续增长。正是在老年人口中发生了最大的变化和挑战。2型糖尿病是一种典型的以胰岛素抵抗为特征的代谢性疾病，主要由高能量摄入和低能量消耗共同引起。因此，个人通常超重(身体质量指数高)，体力活动水平低。在印度人中，有第二类人有类似的新陈代谢状况，但并不超重--被称为“代谢性肥胖”。在这里，脂肪似乎聚集在通常与脂肪沉积无关的区域。其中一个区域是骨骼肌。肌肉在新陈代谢健康中起着至关重要的作用。它是人体内最大的葡萄糖储藏量和最大的使用量，提供了与缺乏运动的明确联系。这个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了解。它将通过确定55岁以上代表两种不同代谢表型的印度人(以及健康对照组)的骨骼肌代谢/脂肪特征，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的关系来实现这一点。它将对表现出两种不同代谢类型的印度人的骨骼肌代谢(代谢体)和线粒体表型(呼吸功能、蛋白质组、转录组)进行比较。它将寻求建立在培养(体外)中研究的肌源性细胞(肌母细胞和成纤维细胞)中的脂肪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，它将把上述措施与针对居住在英国的第二代/第三代印度人的类似措施进行比较。最后，该项目将进行纵向研究，以调查干预计划的效果，该计划使用有针对性的营养补充，结合有氧和力量训练运动，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。

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.