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. We 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. We will determine within-individual variability in cytokine
measurements and describe the kinetics of cytokine response to BCG. We will compare peak
response levels, time to peak, and patterns of cytokines expressed.
Specific Aim 2: To evaluate the effect of hyperglycemia on the cytokine response of type 2
diabetics. We 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. We 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.
Inclusion Criteria:Type 2 diabetes or healthy individual Able to give consent US-born Age
30-65 Exclusion Criteria:* Immunosuppressive disease
- Immunosuppressive medications
- Renal failure
- Advanced pulmonary disease
- Prior BCG vaccination
- Prior TB infection
- Type 1 diabetes