Mechanisms of insulin resistance in South Asians (MIRSA): the roles of skeletal muscle microvasculature and mitochondrial metabolism

点击翻译按钮获取中文摘要

Type 2 diabetes is a major public health problem with worldwide cases projected to rise from ~400 million, currently, to ~600 million by 2035. The risk of diabetes is not consistent across different ethnic groups with people of South Asian (Indian, Pakistani, Bangladeshi, Sri Lankan) origin, who make up nearly a quarter of the world's population, having 2-4 fold higher rates than white Europeans. South Asians also develop diabetes 5-10 years earlier and at lower body weights than white Europeans. By the age of 70, 30-40% of South Asians have diabetes. A key factor influencing risk of type 2 diabetes is a reduction in the ability of muscle to respond appropriately to insulin to take up glucose (sugar) from the blood. This is termed insulin resistance. There is growing evidence that lower levels of fitness and capacity of muscle to burn fat (compared with white Europeans) contributes to South Asians' insulin resistance and higher diabetes risk, but the extent to which this can be improved by exercise is unclear. The main aim of the current proposal, which combines expertise from world-leading groups across three UK Universities, is to determine the extent to which insulin resistance can be improved by an exercise training intervention in South Asian adults, and to identify specific changes in muscle which are responsible for this improvement.The current proposal is a randomised controlled trial in which 44 South Asian adults at increased risk of diabetes will be randomly assigned to either a 12-week exercise training intervention or 12-weeks of usual lifestyle (control). We will assess the effects of the intervention on insulin resistance, using the gold-standard method, called a euglycaemic hyperinsulinaemic clamp, which measures how well the hormone insulin enables glucose to be removed from the blood. We will also use state-of-the-art techniques to identify how exercise training improves insulin resistance in South Asians by measuring effects of the exercise intervention on: the ability of muscle to burn fat within organelles within muscle called mitochondria, on the number of small blood vessels within the muscle structure (called the microvasculature), and the ability of these small blood vessels to relax. This knowledge will help to optimise lifestyle-based diabetes prevention interventions in South Asians, as well as helping to identify potential new treatment approaches.