Impact of Bariatric Surgery on Long-term Diabetes Remission and Complications

描述（由申请人提供）：我们拟议研究的目的是调查Roux-en- y胃旁路手术（RYGB）后短暂的糖尿病缓解期是否会对长期微血管和大血管疾病结局产生持续获益。我们的项目将是我们最近在这一领域的研究的扩展，我们利用来自HMO研究网络（HMORN）中四个大型综合健康计划和护理提供系统的电子病历数据来检查9，000多名严重肥胖的2型糖尿病患者的短期和长期健康结果，这些患者在18年期间（1996-2014）接受了RYGB。这些HMORN研究中心提供的纵向队列和丰富的临床和管理数据对于进行有效、稳健的减肥手术纵向研究至关重要，因为需要进行广泛的调整、分层和亚组设置。对于我们在这里提出的新应用，我们建议在规模、随访持续时间和临床重要结局数量方面扩展和扩大我们之前的队列。我们将把初始队列的随访期延长6年，以进一步提高我们描述糖尿病长期并发症的能力。我们将通过利用以前未使用的数据源- H1,000名在Group Health Cooperative接受RYGB治疗的糖尿病成年人来增加队列的规模。最后，我们的主要创新将是通过一系列分析来探索RYGB的遗留效应，这些分析描述了三个患者组的长期、微血管和大血管结局：RYGB后糖尿病未缓解的患者; RYGB后糖尿病持续缓解的患者;以及初始缓解后糖尿病复发的患者。微血管结局将包括以下内容：（i）肾脏疾病：肾小球滤过率降低和微量/大量白蛋白尿;以及（ii）眼部疾病：糖尿病视网膜病变和临床显著性黄斑水肿。大血管结局将包括以下内容：（i）心肌缺血、梗死、血管成形术/支架植入术或冠状动脉旁路手术;（ii）卒中或短暂性脑缺血发作和（iii）外周血管疾病相关溃疡、血运重建或截肢。本研究将检验以下新假设：（一）重度肥胖患者在RYGB治疗后糖尿病持续缓解，微血管和大血管并发症的发生率较低，不能缓解他们的糖尿病，（2）RYGB后短暂的糖尿病缓解期的有益效果将在糖尿病复发后持续（遗留效应）;即，复发患者的并发症会比 RYGB后糖尿病未缓解的患者，以及（3）RYGB后糖尿病缓解和/或控制的持续时间将与微血管和大血管并发症的发生风险显著相关。 公共卫生相关性：UKPDS和DCCT研究之前已经表明，相对较好的血糖控制的短暂时期在减少微血管和大血管并发症方面产生了显著的长期获益，即使在随机化期结束时干预受试者和对照受试者的血糖控制水平最终变得相同。在这些研究中观察到的改善血糖控制的长期有益作用被称为“遗留效应”或“代谢记忆”。“我们提出的研究的目标是调查减肥手术是否会引起遗留效应。

DESCRIPTION (provided by applicant): The goal of our proposed study is to investigate whether a transient period of diabetes remission after roux-en- y gastric bypass surgery (RYGB) induces a sustained benefit in long-term microvascular and macrovascular disease outcomes. Our project would be an expansion of our recent research in this area in which we utilize electronic medical record data from four large, integrated health plans and care delivery systems in the HMO Research Network (HMORN) to examine short and long-term health outcomes of over 9,000 severely obese individuals with type 2 diabetes who have undergone RYGB over an 18-year period (1996-2014). The longitudinal cohorts and rich, clinical and administrative data available at these HMORN sites are crucial for conducting valid, robust longitudinal studies of bariatric surgery because extensive adjustments, stratification, and sub-setting that are required. For our new application presented here, we propose to extend and expand our prior cohort in terms of size, duration of follow-up, and the number of clinically-important outcomes addressed. We will increase the follow- up period for our initial cohort by six years to further improve our ability to characterize the longer-term complications of diabetes. We will increase the size of our cohort by tapping a previously unutilized data source - H1,000 adults with diabetes who received RYGB at Group Health Cooperative. Finally, our major innovation will be to explore the legacy effect of RYGB through a series of analyses that characterize long- term, micro- and macrovascular outcomes across three patient groups: those who do not remit their diabetes after RYGB; those who experience durable diabetes remission after RYGB; and those who relapse their diabetes after an initial remission. Microvascular outcomes will include the following: (i) renal disease: decreased glomerular filtration rate and micro/macroalbuminura; and (ii) eye disease: diabetic retinopathy and clinically significant macular edema. Macrovascular outcomes will include the following: (i) cardiac ischemia, infarction, angioplasty/stent, or coronary bypass surgery; (ii) stroke or transient ischemic attack and (iii) peripheral vascular disease-related ulceration, revascularization or amputation This study will test the following novel hypotheses: (1) severely obese patients who experience a durable remission of diabetes after RYGB will have fewer incident microvascular and macrovascular complications compared to those who do not remit their diabetes, (2) the beneficial effects of a transient period of diabetes remission after RYGB will persist after diabetes relapse (legacy effect); i.e., relapsing patients will experience fewer complications than those who do not remit their diabetes after RYGB, and (3) the duration of diabetes remission and/or control after RYGB will be significantly associated with the risk of incident microvascular and macrovascular complications. PUBLIC HEALTH RELEVANCE: The UKPDS and the DCCT studies have previously shown that transient periods of relatively better glycemic control resulted in significant long-term benefits in terms of reduced microvascular and macrovascular complications, even though the levels of glycemic control eventually became identical between intervention and control subjects when the randomization period ended. The prolonged beneficial effects of improved glycemic control observed in these studies have been termed the "legacy effect" or "metabolic memory." The goal of our proposed study is to investigate whether there is a legacy effect induced by bariatric surgery.