This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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