Does Hyperglycemia Predict Pancreatic Cancer Diagnosis?

描述(申请人提供)：胰腺癌在高达80%的患者中会导致葡萄糖不耐受和糖尿病。胰腺癌诱发糖尿病(PaCDM)通常无症状，病程短(3年)，发生在癌症的可切除阶段。高达1%的新诊断的糖尿病患者，相当于或&>50岁，可能患有PaCDM。我们建议确定新升高的空腹血糖(FBG)是否指示潜在的胰腺癌，这是在FBG测量后3年内诊断为胰腺癌的证据。如果是这样的话，这将为筛查散发性胰腺癌提供一种全新的方法。我们假设受试者3年内被诊断为胰腺癌的可能性很高：a)等于或等于50岁且有新的空腹血糖升高，b)有已知的胰腺癌危险因素(如吸烟)的空腹血糖升高，和/或c)在连续测量中表现出空腹血糖随时间的突然增加。我们将确定在1988年至2002年期间前往梅奥诊所就诊的年龄等于或等于50岁的受试者，这些受试者居住在梅奥诊所周围的集水区，并进行了包括空腹血糖在内的常规体检。初步数据显示，在此期间，约有15万名不同的受试者进行了30万次这样的访问，提供了100万人年的后续行动。我们将以电子方式检索临床和实验室数据，并检查自FBG测量之日起的3年随访，以确定那些被诊断为胰腺癌的人。我们预计这一队列中有340至510例胰腺癌病例。我们的具体目标是：目标1A)。测试常规体检时抽取的空腹血糖是否能预测潜在的胰腺癌的可能性，并测试这种相关性的非线性。目的1B)建立一个预测胰腺癌3年内诊断可能性较高的空腹血糖阈值。目标2)。评估已知的胰腺癌风险因素(年龄、吸烟、肥胖和家族史)在多大程度上改变了空腹血糖高于AIM 1B定义的阈值的潜在胰腺癌的可能性。目标3)。为了测试空腹血糖随时间变化的模式是否可以预测潜在的胰腺癌的可能性。这项研究的临床和研究意义重大。这些数据可能会勾勒出哪些人患有胰腺癌的可能性很高，哪些人可能是更密集的筛查或早期发现方案的理想候选者。本申请中描述的研究与胰腺癌100%相关。

DESCRIPTION (provided by applicant): Pancreatic cancer causes glucose intolerance and diabetes in up to 80% of patients. Pancreatic cancer induced diabetes (PaCDM) is often asymptomatic, of short duration (<3 years), and occurs at a resectable stage of the cancer. Up to 1% of newly diagnosed diabetics, equal to or >50 years of age may have PaCDM. We propose to establish whether newly elevated fasting blood glucose (FBG) is indicative of underlying pancreatic cancer as evidenced by diagnosis of pancreatic cancer within 3 years of the FBG measurement. If so, this would provide an entirely novel approach to screening for sporadic pancreatic cancer. We hypothesize that the 3-year likelihood of diagnosis of pancreatic cancer will be high in subjects: a) equal to or > 50 years of age with newly elevated FBG, b) with elevated fasting glucose who have known risk factors for pancreatic cancer (e.g. smoking), and/or c) who manifest an abrupt increase in FBG in serial measurements over time. We will identify visits to Mayo Clinic between years 1988 to 2002 by subjects equal to or >50 years of age who resided in its surrounding catchment area and had a routine physical examination that included a FBG. Preliminary data reveal that about 150,000 different subjects made >300,000 such visits during this time period providing >1 million person-years of follow-up. We will electronically retrieve clinical, and laboratory data and examine 3-year follow-up from date of FBG measurement to identify those diagnosed with pancreatic cancer. We expect 340 to 510 pancreatic cancer events in this cohort. Our Specific Aims are: Aim 1A). To test if FBG drawn during routine physical examination predicts likelihood of underlying pancreatic cancer and to test for non-linearity of this association. Aim 1B) To establish a FBG threshold that predicts a high 3-year likelihood of diagnosis of pancreatic cancer. Aim 2). To estimate the extent to which known risk factors for pancreatic cancer (age, smoking, obesity and family history) modify the likelihood of underlying pancreatic cancer in subjects with FBG greater than the threshold defined by Aim 1B. Aim 3). To test if patterns of change in serial measurements of FBG over time predict likelihood of underlying pancreatic cancer. The clinical and research implications of this study are considerable. These data may lead to delineation of individuals who have a high likelihood of existing pancreatic cancer, and who may be ideal candidates for more intensive screening or early detection regimens. The research described in this application is 100% relevant to pancreatic cancer.