The Effect of Exogenous Insulin Therapy on Colorectal Adenoma Risk among PTS

描述（由申请人提供）： 胰岛素抵抗导致的胰岛素水平升高可能是2型糖尿病（DM）患者结直肠癌（CRC）风险增加的原因。由于注射胰岛素在控制高血糖方面的效率低下，需要胰岛素的2型DM患者暴露于甚至更高的全身胰岛素水平。我们最近报道，接受胰岛素治疗的2型糖尿病患者发生CRC的风险比其他2型糖尿病患者高2倍以上。此外，我们和其他人的初步横断面数据表明，外源性胰岛素治疗可能与结直肠腺瘤患病率增加有关。我们推测胰岛素治疗可能增加2型糖尿病患者晚期腺瘤复发的风险。具体来说，我们假设在息肉切除术后监测计划中被视为“低风险”（即1或2个小管腺瘤）的胰岛素使用者可能发生复发性腺瘤的风险更高，并且可能需要比目前推荐的间隔更短的监测结肠镜检查。主要目的是：1）根据胰岛素暴露状态和糖尿病状态估计晚期腺瘤复发的绝对风险，2）在接受息肉切除术后监测结肠镜检查的2型糖尿病退伍军人和非退伍军人队列中，确定胰岛素暴露是否可预测晚期腺瘤复发。研究患者将从两个密切相关机构的电子病历系统中识别：费城退伍军人管理局医疗中心和宾夕法尼亚大学卫生系统。将对两个研究中心的患者进行单独分析和合并分析。将从电子内窥镜检查和医学数据库中提取结局数据。将通过数据库查询和患者访谈获得胰岛素治疗暴露和其他协变量的信息。我们的初步数据表明，我们有必要的人员，环境，数据来源和样本量来实现我们的目标。CRC是美国第二大致命癌症。与此同时，2型糖尿病在美国流行，尤其是在患病率为20%的退伍军人中。此外，VA系统中37%的DM患者正在接受胰岛素治疗，其余大多数患者最终将需要胰岛素来充分控制血糖。由于缺乏直接证据，目前的CRC监测指南不建议缩短这些患者的监测间隔。这项研究是第一项专门针对这一重要问题的研究。其研究结果将有可能改变退伍军人和美国人口中大量胰岛素使用者的息肉切除术后监测实践。

DESCRIPTION (provided by applicant): Elevated insulin levels in response to insulin resistance may be responsible for the increased risk of colorectal cancer (CRC) among patients with type 2 diabetes mellitus (DM). Insulin-requiring type 2 DM patients are exposed to even higher systemic insulin levels due to the inefficiency of injected insulin in controlling hyperglycemia. We recently reported that the risk of CRC is over 2-fold higher among type 2 DM patients receiving insulin therapy than among other type 2 DM patients. In addition, preliminary cross-sectional data from us and others have suggested that exogenous insulin therapy may be associated with an increased prevalence of colorectal adenoma. We hypothesize that insulin therapy may increase the risk of advanced adenoma recurrence among type 2 DM patients. Specifically, we hypothesize that insulin users who are regarded as "low-risk" (i.e, 1 or 2 small tubular adenomas) in a post-polypectomy surveillance program may be at a higher risk of developing recurrent adenoma and may require surveillance colonoscopies at a shorted interval than what is currently recommened. The primary aims are 1) to estimate the absolute risk of advanced adenoma recurrence according to insulin exposure status and diabetes status and 2) to determine whether insulin exposure predicts advanced adenoma recurrence, among a cohort of veterans and non-veterans with type 2 DM who are undergoing post- polypectomy surveillance colonosocopy. Study patients will be identified from the electronic medical record systems of two closely affiliated institutions: the Philadelphia Veteran's Administration Medical Center and the University of Pennsylvania Health System. Patients from the two sites will be analyzed both separately and pooled together. Outcome data will be extracted from the electronic endoscopy and medical databases. Information on exposure to insulin therapy and other covariates will be obtained by database query and a patient interview. Our preliminary data indicated that we have the necessary personnel, environment, data source, and sample size to achieve our aims. CRC is the second most lethal cancer in the U.S. In the meantime, there is an epidemic of type 2 DM in the U.S., particularly among the veterans with 20% prevalence. Furthermore, 37% of the patients with DM in the VA system are on insulin therapy, and most of the remaining patients will eventually require insulin for adequate glucose control. Due to a lack of direct evidence, the current CRC surveillance guidelines do not recommend shorter surveillance intervals for these patients. The proposed study is the first study specifically designed to investigate this important question. Its findings will have the potential to change the post-polypectomy surveillance practices among the enormous population of insulin users in the veteran and the US population.