Immunobiology of Diabetes and Tuberculosis

The study hypothesis is that type 2 diabetics have abnormal cell-mediated immunity to tuberculosis manifesting as altered cytokine responses by peripheral blood mononuclear cells (PBMCs). This hypothesis will be tested using the live tuberculosis vaccine, Bacille Calmette-Guerin (BCG), in U.S.-born type 2 diabetics and nondiabetics. The investigators will control for potential confounding by age, sex, race, comorbidities, and select medications. Expression of key cytokines will be measured with real-time polymerase chain reaction.

The project has three specific aims:

Specific Aim 1: To assess differences between the study groups in cytokine expression before and after BCG vaccination. The investigators will determine within-individual variability in cytokine measurements and describe the kinetics of cytokine response to BCG. Peak response levels, time to peak, and patterns of cytokines expressed will be compared.

Specific Aim 2: To evaluate the effect of hyperglycemia on the cytokine response of type 2 diabetics. The investigators will evaluate whether levels of hemoglobin A1C (HbA1C) are associated with degree of cytokine response and test if type 2 diabetics who have good glucose control are different from nondiabetics.

Specific Aim 3: To evaluate the effect of testing PBMCs from diabetics outside of their diabetic milieu. Investigators will compare the BCG-specific cytokine responses of PBMCs stimulated in normal medium, PBMCs stimulated in glucose correlating to the person's most recent HbA1C, and whole blood samples.