DIABETES ON CYTOKINE RESPONSE TO BACILLE CALMETTE GUERIN VACCINATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尽管有报道称，2型糖尿病在美国和墨西哥的结核病（TB）病例中占25%，但很少有研究关注这种关联的潜在机制。该研究假设2型糖尿病患者的结核病发病率较高是由于结核特异性细胞免疫的改变。为了直接测试这一点，将给17名2型糖尿病患者和17名对照者接种结核病活疫苗卡介苗（BCG）。然后将使用实时聚合酶链反应测量其外周血单核细胞（PBMC）的细胞因子应答。拟议的试点研究有两个具体目标：（1）检查细胞因子测量的个体内变异性和细胞因子对BCG反应的动力学;（2）使用从糖尿病环境中分离的PBMC验证细胞因子测量。参与者将被跟踪六个月。将计算细胞因子表达的平均值和方差，并使用广义混合效应模型创建响应曲线。将比较正常培养基中刺激的PBMC、葡萄糖升高培养基中的PBMC和全血样本之间的细胞因子表达。该试验将提供样本量和最佳采样时间的估计值，并验证对该人群分离的PBMC的研究。它将为下一步建立必要的基础，这是一项仔细解决潜在混杂因素的研究，以更好地分离糖尿病，慢性高血糖症和胰岛素水平对TB特异性细胞免疫的影响。这一有价值的信息在预防糖尿病感染和结核病疫苗开发方面具有普遍的应用。

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. Despite reports that type 2 diabetes contributes as much as 25% of tuberculosis (TB) cases in the U.S. and Mexico, few studies have focused on the underlying mechanism of this association. The study hypothesis is that higher rates of TB in type 2 diabetics are due to altered TB-specific cellular immunity. To directly test this, the live TB vaccine, Bacille Calmette-GuTrin (BCG), will be given to 17 type 2 diabetics and 17 controls. The cytokine responses of their peripheral blood mononuclear cells (PBMCs) will then be measured with real-time polymerase chain reaction. The proposed pilot study has two specific aims: (1) to examine within-individual variability of cytokine measurements and the kinetics of cytokine response to BCG; and (2) to validate cytokine measurements using PBMCs isolated from the diabetic milieu. Participants will be followed for six months. Mean and variances of cytokine expression will be calculated and response curves will be created with generalized mixed-effects models. Cytokine expression will be compared between stimulated PBMCs in normal medium, PBMCs in medium with elevated glucose, and whole blood samples. This pilot will provide estimates of sample size and optimal sampling times, and validate the study of isolated PBMCs from this population. It will establish the necessary groundwork for the next step, which is a study that carefully addresses potential confounders to better isolate the effect of diabetes, chronic hyperglycemia, and insulin levels on TB-specific cellular immunity. This valuable information has general applications in preventing infections that afflict diabetics and in TB vaccine development.