Does Hyperglycemia Predict Pancreatic Cancer Diagnosis?

描述（由申请人提供）：胰腺癌导致高达80%的患者发生葡萄糖耐受不良和糖尿病。胰腺癌诱发的糖尿病（PaCDM）通常无症状，持续时间短（<3年），并且发生在癌症的可切除阶段。高达1%的新诊断的糖尿病患者，等于或>50岁，可能患有PaCDM。我们建议确定新的空腹血糖（FBG）升高是否是潜在胰腺癌的指标，如FBG测量后3年内胰腺癌的诊断所证明的。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，在以下受试者中，胰腺癌的3年诊断可能性较高：a）年龄等于或> 50岁且FBG新近升高，B）空腹血糖升高且具有已知的胰腺癌风险因素（例如吸烟），和/或c）在连续测量中随时间推移FBG突然升高。我们将确定1988年至2002年期间，居住在马约诊所周围集水区的年龄等于或大于50岁的受试者前往该诊所就诊，并进行了包括FBG在内的常规体格检查。初步数据显示，在这段时间内，约有150，000名不同的受试者进行了> 300，000次此类访问，提供了> 100万人年的随访。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，以确定诊断为胰腺癌的患者。我们预计该队列中有340至510例胰腺癌事件。我们的具体目标是：目标1A）。检测常规体格检查期间采集的FBG是否可预测潜在胰腺癌的可能性，并检测该相关性的非线性。目的1B）建立一个FBG阈值，预测胰腺癌诊断的3年高可能性。目标2）。估计已知的胰腺癌风险因素（年龄、吸烟、肥胖和家族史）对FBG大于目标1B定义的阈值的受试者中基础胰腺癌可能性的影响程度。目标3）。检测FBG连续测量值随时间的变化模式是否可预测潜在胰腺癌的可能性。这项研究的临床和研究意义是相当大的。这些数据可能会导致对具有高可能性的现有胰腺癌的个体进行描绘，并且可能是更密集筛查或早期检测方案的理想候选人。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.