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

南亚人胰岛素抵抗机制（MIRSA）：骨骼肌微血管和线粒体代谢的作用

• 批准号: MR/R023247/1
• 负责人: Jason Gill
• 金额: $ 83.34万
• 依托单位: University of Glasgow
• 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: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR023247%2F1
• 关键词: Mechanisms; insulin; resistance; South; Asians

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.

2型糖尿病是一个主要的公共卫生问题，预计全球病例将从目前的约4亿增加到2035年的约6亿。糖尿病的风险在不同种族群体中并不一致，南亚人（印度人，巴基斯坦人，孟加拉国人，斯里兰卡人）占世界人口的近四分之一，比白色欧洲人高2-4倍。南亚人患糖尿病的时间也比欧洲白色人早5-10年，体重也比欧洲人轻。到70岁时，30-40%的南亚人患有糖尿病。影响2型糖尿病风险的一个关键因素是肌肉对胰岛素适当反应的能力降低，从而从血液中摄取葡萄糖（糖）。这被称为胰岛素抵抗。越来越多的证据表明，较低的健康水平和肌肉燃烧脂肪的能力（与白色欧洲人相比）导致了南亚人的胰岛素抵抗和较高的糖尿病风险，但运动能在多大程度上改善这一点尚不清楚。目前提案的主要目的是结合英国三所大学的世界领先团体的专业知识，确定南亚成年人通过运动训练干预可以改善胰岛素抵抗的程度，目前的建议是一项随机对照试验，在该试验中，44名患有糖尿病风险增加的南亚成年人，将被随机分配到12周的运动训练干预或12周的日常生活方式（对照）。我们将评估干预对胰岛素抵抗的影响，使用金标准方法，称为正常血高胰岛素钳夹，该方法测量激素胰岛素使葡萄糖从血液中清除的程度。我们还将使用最先进的技术来确定运动训练如何改善南亚人的胰岛素抵抗，方法是测量运动干预对以下方面的影响：肌肉燃烧肌肉内细胞器（称为线粒体）内脂肪的能力，肌肉结构内小血管（称为微血管）的数量，以及这些小血管放松的能力。这些知识将有助于优化南亚人基于生活方式的糖尿病预防干预措施，并有助于确定潜在的新治疗方法。