BREAST CANCER LYMPHEDEMA: ROLE OF INSULIN RESISTANCE/FOXC2

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。 假设： 它假设：1)对晚期乳腺癌幸存者的胰岛素敏感性进行定量评估，将表现为同侧手臂水肿的临床证据的受试者与没有同侧手臂水肿的受试者平均分配，以及2)相对胰岛素抵抗(IR)的存在与乳腺癌相关淋巴水肿表达的相关性，将导致未来制定适当的风险分层和有针对性的治疗干预措施。 此外，我们将对每个患者的FOXC2基因进行测序，包括未翻译的5‘区，以确定可能与IR和淋巴水肿风险相关的潜在多态。 实验设计： 在最初的访问中，每个研究对象都将接受一般健康的临床评估，包括体检，并根据四肢周长的卷尺估计上肢体积。将获得用于FOXC2基因分析的外周血液样本。 在第二次访问中，将进行胰岛素敏感性评估。胰岛素促进葡萄糖摄取的能力将通过最初描述的胰岛素抑制试验(IST)的改进来评估。在隔夜禁食后，哈佛输液泵将以25g/小时的速度给含有2.5%(w/v)人血清白蛋白的溶液中的奥曲肽注射，以抑制内源性胰岛素的分泌。同时，胰岛素和葡萄糖的输注速度分别为25mU/m2/min和240 mg/m2/min。血液将每半小时采样一次，直到测试开始150分钟，然后在测试的最后30分钟内每10分钟采样一次。 在第三次(最后一次)检查中，每个受试者都将接受标准的口服葡萄糖耐量测试。在隔夜禁食后，将给予75g口服葡萄糖负荷，随后在0、30、60、120和180分钟采集静脉血。

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. Hypothesis: It is hypothesized that: 1) a quantitative assessment of insulin sensitivity in late breast cancer survivors, equally divided among subjects who display clinical evidence of ipsilateral arm edema and those that do not, and 2) correlation of the presence of relative insulin resistance (IR) to the expression of breast cancer-associated lymphedema, will lead to future elaboration of appropriate risk stratification and targeted therapeutic interventions. Additionally, we will sequence the FOXC2 gene, including the untranslated 5' region, in each patient to identify potential polymorphisms that might correlate both to the presence of IR and lymphedema risk. Experimental Design: In the initial visit, each study subject will undergo clinical assessment of general health, including a physical examination, and evaluation of upper extremity volume, estimated from tape measurements of limb circumference. A peripheral blood sample will be obtained for analysis of the FOXC2 gene. In the second visit, assessment of insulin sensitivity will be performed. The ability of insulin to promote glucose uptake will be estimated by a modification of the insulin suppression test (IST) as originally described. After an overnight fast, octreotide in a solution containing 2.5% (w/v) human serum albumin will be administered at a rate of 25 ¿g/hr by a Harvard infusion pump, to suppress endogenous insulin secretion. Simultaneously, insulin and glucose will be infused at 25 mU/m2/min and 240 mg/m2/min, respectively. Blood will be sampled every half hour until 150 min into the test, and then every ten min in the last 30 min of the test. In the third (last) visit, each subject will undergo a standard oral glucose tolerance test. After an overnight fast, a 75 g oral glucose load will be administered, with subsequent venous blood collection at times 0, 30, 60, 120, and 180 min.