Obesity complicating type 1 diabetes in young people: Physiology and Impact of GLP-1 analogue anti-obesity treatment on cardiometabolic risk factors

项目摘要/摘要 本研究旨在研究GLP-1类似物肥胖治疗对高血压的作用机制。 青年1型糖尿病(T1D)合并肥胖患者的可改变心脏代谢危险因素 通过对脂肪、血糖和脂质生理学的评估。 肥胖和超重影响40%患有T1D的青少年和年轻人，其中T1D 仅此一项就已经大大增加了未来患心血管疾病的风险。我们的初步数据显示 不考虑体重指数类别，大多数患有T1D的青少年的内脏脂肪组织与皮下脂肪组织的比例 与患有肥胖症和糖尿病前期的年轻人一样高。患有T1D的年轻人的这一内脏脂肪比率与 肝脏胰岛素抵抗程度。 该研究将全面评估患有T1D和T1D的年轻人心脏代谢危险因素的驱动因素。 同时检测GLP-1类似肥胖症治疗对内脏脂肪组织的影响(比率 内脏到内脏+皮下脂肪组织)、胰岛素抵抗和餐后脂血症。要实现 为了达到这些目标，我们将利用1)腹部MRI来量化腹部脂肪分布，2)阶梯状 稳定同位素示踪剂的正常血糖高胰岛素钳夹评估胰岛素抵抗和 糖异生，3)测量身体成分的DEXA扫描，以及4)高脂肪混合膳食耐量试验 量化餐后致动脉粥样硬化脂蛋白的变化。在完成这些评估后，54名年轻人 符合减肥药物治疗标准的成人T1D和肥胖患者将被随机分为1- 口服赛马路德或安慰剂治疗一年。代谢评估将在一年内重复进行 治疗。由15名患有T1D和瘦体重指数的年轻人组成的对照组将接受 一次性新陈代谢研究。 执行拟议的研究计划对于促进对以下策略的理解至关重要 降低心脏代谢风险并影响促进心脏代谢风险的病理生理机制 T1D和肥胖的年轻患者。这与NIDDK改善健康和健康的使命是一致的 糖尿病患者的生活质量。结果将揭示心脏代谢性疾病风险和 T1D合并肥胖的年轻人的潜在治疗方法。

PROJECT SUMMARY/ABSTRACT This proposal aims to characterize the impact of GLP-1 analogue obesity treatment on mechanisms of modifiable cardiometabolic risk factors in young people with type 1 diabetes (T1D) complicated by obesity through assessment of adipose, glucose, and lipid physiology. Obesity and overweight impact 40% of adolescents and young adults with T1D, a population in whom T1D alone already drastically increases future cardiovascular disease risk. Our preliminary data indicate that regardless of BMI category, most adolescents with T1D have a visceral to subcutaneous adipose tissue ratio as high as youth with obesity and prediabetes. This visceral fat ratio in youth with T1D is proportional to the degree of hepatic insulin resistance. The study will comprehensively assess drivers of cardiometabolic risk factors in young people with T1D and obesity while examining the impact of GLP-1 analogue obesity treatment on visceral adipose tissue (the ratio of visceral to visceral+subcutaneous adipose tissue), insulin resistance, and postprandial lipemia. To achieve these aims, we will utilize 1) an abdominal MRI to quantify abdominal adipose distribution, 2) the stepped euglycemic hyperinsulinemic clamp with stable isotope tracers to assess insulin resistance and gluconeogenesis, 3) a DEXA scan to measure body composition, and 4) a high-fat mixed meal tolerance test to quantify postprandial changes in atherogenic lipoproteins. After completing these assessments, 54 young adults with T1D and obesity who meet the criteria for anti-obesity pharmacotherapy will be randomized to 1- year of treatment with oral semaglutide or placebo. The metabolic assessments will be repeated at 1-year of the treatment. A comparator group of 15 young adults with T1D and lean body mass index will undergo the metabolic studies at one-time point. Carrying out the proposed research program is critical to advance the understanding of the strategies to reduce cardiometabolic risk and impact the pathophysiologic mechanisms promoting cardiometabolic risk in young patients with T1D and obesity. This is consistent with the NIDDK's mission to improve the health and quality of life of individuals with diabetes. Results will reveal the intricacies of cardiometabolic disease risk and potential treatment in young people with T1D complicated by obesity.