Surgical or Medical Treatment for Pediatric Type 2 Diabetes (ST2OMP)

项目总结 青年起病的2型糖尿病(T2D)导致早期外源性胰岛素依赖和T2D的进展 合并症，包括血脂异常、高血压、非酒精性脂肪肝和糖尿病肾病。 放松点。青少年T2D的病理生理学与成人和目前的治疗方法有很大的不同。 对年轻人来说是不够的。因此，探索减少并存的创新方法至关重要。Meta- 波尔奇减肥手术(MBS)显著改善了患有T2D的成人患者的多种结局。一开始很小，松果- Roux-en-Y胃分流术的TROLLIC研究也表明对年轻人T2D有有益的影响，但肯定的是 对青年发病的T2D的发病机制缺乏研究和了解，特别是在现在更多的青少年发病的情况下。 Mon形式，垂直袖状胃切除术(VSG)。我们的长远目标是改善青少年的待遇- 启动T2D以减少发病率和死亡率。我们的中心假设是VSG将更有效地减少- 血糖和合并症比目前最好的医疗治疗更好：高级药物治疗 (AMT)，通过胰腺、肠肝和/或代谢变化。为了检验这一假设，我们将招收90名- 比较VSG和AMT对血糖控制和T2D-AS-AS的影响。 相关的共病，以及潜在的机制。我们的网站有合作的儿科医疗和 外科专业知识，包括在MBS和T2D中使用非侵入性代谢措施，并共同拥有 庞大、多样化的青少年T2D队列，使我们处于实现这些目标的独特地位。我们的理论基础 1)迫切需要确定VSG对青年发病的T2D患者AMT的影响，以及2)IM- 对MBS潜在影响的机制的证实知识将指导未来的非手术治疗 不那么咄咄逼人地模仿MBS。目的1将评估VSG与AMT对血糖控制和T2D-1的影响。 相关的共病。我们假设患有T2D的年轻人接受VSG与AMT的比例更高 将达到HbA1c；lt；6%的主要终点，并伴有更高的缓解率(更低的发病率)。 平局分别为1岁和2岁。我们还将探讨T2D持续时间、BMI、性别和初始HbA1c对PRI的影响。 玛丽的结局。目的2将阐明VSG和AMT影响胰岛细胞功能的机制。 肠肝代谢和组织特异性胰岛素敏感性及其在血糖控制中的作用 患有T2D的年轻人。我们假设β-细胞功能的初步结果将在T2D青年经历- ING VSG与AMT分别为1年和2年。次要终点包括全身IR、组织特异性IR、胰岛素抵抗 Respse和α-cell功能，以了解潜在的改进机制。这些结果将决定 MBS在促进血糖控制和减少青年并发症方面是否比AMT更有效- 出现T2D，这一结果将极大地改善目前进展缓慢的年轻人的生活- 姐姐。此外，这项建议将有助于了解青少年住房抵押贷款证券化的潜在机制，指导制定- 未来的治疗可以针对这些相同的途径，而不需要手术。

PROJECT SUMMARY Youth-onset type 2 diabetes (T2D) leads to early dependence on exogenous insulin and progression of T2D co-morbidities, including dyslipidemia, hypertension, non-alcoholic fatty liver disease and diabetic kidney dis- ease. The pathophysiology of T2D in youth differs considerably from adults and current treatment approaches are inadequate for youth. Thus, exploration of innovative approaches to reduce co-morbidities is critical. Meta- bolic bariatric surgery (MBS) significantly improves multiple outcomes in adults with T2D. Initial small, uncon- trolled studies of Roux-en-Y gastric bypass also suggest beneficial effects in youth with T2D, but definitive studies and understanding of mechanisms in youth-onset T2D are lacking, especially with the now more com- mon form of MBS, vertical sleeve gastrectomy (VSG). Our long-term goal is to improve the treatment of youth- onset T2D to reduce morbidity and mortality. Our central hypothesis is that VSG will be more effective in reduc- ing glycemia and comorbidities than the best currently available medical treatment: advanced medical therapy (AMT), via pancreatic, enterohepatic and/or metabolic changes. To test this hypothesis, we will enroll 90 ado- lescents with T2D across two sites and compare the effects of VSG vs. AMT on glycemic control and T2D-as- sociated comorbidities, as well as underlying mechanisms. Our sites have collaborative pediatric medical and surgical expertise, including use of non-invasive metabolic measures in MBS and T2D and collectively have a large, diverse adolescent T2D cohort, making us uniquely positioned to accomplish these aims. Our rationale is that 1) there is a critical need to determine the impact of VSG over AMT in youth-onset T2D, and 2) im- proved knowledge of the mechanisms underlying the impact of MBS will direct future non-surgical approaches to mimic MBS less invasively. Aim 1 will evaluate the effects of VSG vs. AMT on glycemic control and T2D- associated co-morbidities. We hypothesize that a higher proportion of youth with T2D receiving VSG vs. AMT will achieve the primary endpoint of HbA1c <6% with higher rates of remission (lower incidence) of comorbidi- ties at 1 and 2 years. We will also explore the impact of T2D duration, BMI, sex and initial HbA1c on the pri- mary outcome. Aim 2 will elucidate mechanisms by which VSG & AMT influence pancreatic islet cell function, enterohepatic metabolism and tissue-specific insulin sensitivity, and their contributions to glycemic control in youth with T2D. We hypothesize that the primary outcome of β-cell function will improve in T2D youth undergo- ing VSG vs. AMT at 1 and 2 years. Secondary endpoints include whole-body IR, tissue-specific IR, incretin re- sponse and α-cell function to understand mechanisms underlying improvements. These results will determine whether MBS is more effective than AMT in promoting glycemic control and reducing co-morbidities in youth- onset T2D, an outcome that would dramatically improve the lives of youth who currently have a dismal progno- sis. Further, this proposal will help understand the mechanisms underlying MBS in youth, to guide the develop- ment of future treatments that could target these same pathways without the need for surgery.