Immunobiology of Diabetes and Tuberculosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Converging Epidemics: Immunobiology of Diabetes Mellitus and Tuberculosis Infection

Conditions
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Tuberculosis, Diabetes Mellitus

Intervention / Treatment
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* Biological: BCG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Type 2 diabetes or healthy individual Able to give consent US-born Age 30-65 Exclusion Criteria:* Immunosuppressive disease Immunosuppressive medications Pregnancy Renal failure Advanced pulmonary disease Prior BCG vaccination Prior TB infection Type 1 diabetes

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Participants with diabetes<br>Persons with diagnosis of diabetes. Received biological intervention: BCG | Biological: BCG<br>* Both arms: diabetics and nondiabetics will receive vaccination in the upper arm with a 0.1-mg intradermal dose of a single strain of BCG (Mycobax, Sanofi-Aventis), which is FDA approved for this indication.<br>|
| Active Comparator: Participants without diabetes<br>Persons with no diagnosis of diabetes and negative diabetes screening labs. Received biological intervention: BCG. | Biological: BCG<br>* Both arms: diabetics and nondiabetics will receive vaccination in the upper arm with a 0.1-mg intradermal dose of a single strain of BCG (Mycobax, Sanofi-Aventis), which is FDA approved for this indication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antigen-specific Immune Response Measured by Reaction to Tuberculin Skin Test | Participants had baseline tuberculin testing (TST), followed by BCG vaccination, and at 5 months after vaccination, study participants had repeat tuberculin skin testing done. | 5 months | 
| Kinetics of Mycobacterial-specific Immune Response After BCG Vaccination | Blood was sampled at times 0, 2, 4, 6, 8, 12, 16, and 20 weeks post BCG vaccination and Interferon gamma production was measured as change from pre-vaccination baseline. Timeline of peak IFn-g response was measured for both study groups. | 5 months |