CLINICAL TRIAL: EFFECTS OF PIOGLITAZONE ON INCRETIN AXIS IN PTS W TYPE 2 DIABETE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 胰岛素激素是肠道对食物摄取的反应产生的荷尔蒙。这些激素帮助身体控制葡萄糖(糖)的新陈代谢。特别值得一提的是，两种胰岛素激素(GLP-1和GIP)会导致胰腺在高血糖时分泌更多的胰岛素。这有助于身体更有效地代谢葡萄糖，从而降低血糖水平。GLP-1和GIP在2型糖尿病(T2 DM)患者中的作用不如在没有糖尿病的患者中起作用。这项研究测试了一种名为吡格列酮(Actos)的药物是否能改善GIP增加胰岛素分泌的能力。 为了解决这个问题，我们将招募T2 DM患者，他们的糖尿病是通过饮食和运动或二甲双胍(另一种治疗T2 DM的药物)控制的。受试者将通过DEXA扫描测量身体脂肪，并进行一系列研究来表征他们的新陈代谢。这些研究包括口服葡萄糖耐量测试(一种有时用于诊断糖尿病的测试)、混合餐挑战(测量一顿饭产生多少GLP-1和GIP)，以及测量胰岛素分泌对静脉注射葡萄糖和GIP的反应。我们还将使用针头测量GIP受体的水平，从腹部皮肤下获得少量脂肪样本。然后，受试者将被随机分配到12周的治疗中，要么服用吡格列酮，要么服用匹配的安慰剂(一种不含药物的非活性片剂)。在最初的4周内，吡格列酮的剂量将增加到每天45毫克的最大处方剂量。在研究的治疗阶段，受试者将每2-4周接受一次检查。治疗12周后，在研究开始时进行的所有研究都将重复进行。吡格列酮治疗将持续到试验结束，大约4周。 这项研究的结果可能为我们提供有关T2 DM患者血糖控制恶化的信息。这一信息也可能导致预防或治疗T2 DM的新方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM) as in subjects who do not have diabetes. This study tests whether a medicine called pioglitazone (Actos ), which is commonly used to treat T2DM, improves the ability of GIP to increase insulin secretion. To address this question we will recruit patients with T2DM whose diabetes is controlled with either diet and exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of studies to characterize their metabolism. These studies include an oral glucose tolerance test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion in response to glucose and GIP given through a vein. We will also obtain small samples of fat (from just under the skin of the belly) using a needle to measure levels of the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with either pioglitazone or matching placebo (an inactive tablet that does not contain medication). The dose of pioglitazone will be increased during the first 4 weeks to the maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the treatment phase of the study. After 12 weeks of treatment all studies performed at the beginning of the study will be repeated. The pioglitazone treatment will continue until the end of testing, approximately 4 weeks. The results of this study may give us information about why glucose control deteriorates in T2DM. This information might also lead to new ways to prevent or treat T2DM.