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

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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.