Diabetes Mellitus, Type 2, Latent Tuberculosis
Conditions
Keywords
low-grade inflammation, glucose metabolism, body composition, cytokines, adipokines, biomarkers
Brief summary
This study will be investigating the effect of latent tuberculosis infection (LTBI) treatment on glucose tolerance and low-grade inflammation. Almost a century ago, researchers proposed that diabetes (DM) was associated with increased risk of Tuberculosis infection (TB). A more recent systematic review concluded that DM increases the relative risk for TB 3.1 times. Reversely, TB may affect the glycaemic control; TB is in many cases a chronic infection characterised by long term low-grade inflammation and weight loss, and persons with TB are known to be at risk of hyperglycaemia and DM at time of diagnosis. A latent infection with the m.tuberculosis bacteria is silent without symptoms. 1,7 billion have LTBI on a global scale. Event though the infected person does not experience symptoms, increased background inflammation has been shown in LTBI patients in previous studies. We also know that an increase in inflammatory markers precedes clinical development of DM, and that subclinical inflammation contributes to insulin resistance. We hypothesise that LTBI contributes to dysregulated glucose metabolism due to increased low-grade inflammation, and that treatment will reduce low-grade inflammation and improve glucose tolerance.
Interventions
DRUGRifampicin 300 Mg Oral Capsule
Rifampicin 600 mg orally once daily for 4 months
Isoniazid 300 mg daily for 6 months
Sponsors
Herlev and Gentofte Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
The study consists of two arms with different patient populations. Both arms will receive identical treatment. Arm A will have type 2 diabetes and latent tuberculosis infection (LTBI). Group B will not have any form of diabetes, but LTBI.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria for the LTBIDM arm: * 18+ years * Known DM type 2 Inclusion criteria for LTBI arm * 18+ years * LTBI positive * No diagnosis with or known DM (1 and 2)
Exclusion criteria
(both arms) : * Previous treatment for TB or LTBI * Pregnancy * Type 1 DM * Known immunosuppression such as: HIV, steroid treatment within 14 days before inclusion, daily NSAID treatment, ongoing chemotherapy, ongoing immunomodulating treatment or splenectomy * Known contraindication to both study drugs * Known active liver disease * Known severe inflammatory or rheumatological diseases with immune activation and need for prolonged systemic treatment such as IBD, RA, Psoriasis and Wegners granulomatosis * Recent antibiotic treatment (\>2 days) or severe infection within 14 days before enrollment * Known active cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| OGTT (oral glucose tolerance test) | Time Frame: 4-6 months (depending on treatment) | Reduction in plasma glucose area under the curve during OGTT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in insulin production | Time Frame: 4-6 months (depending on treatment) | Insulin/c-peptid, HOMA-B pre and post treatment |
| Changes in insulin resistance | Time Frame: 4-6 months (depending on treatment) | HOMA-IR pre and post treatment |
| Changes in low-grade inflammatory markers and in adipokines | Time Frame: 4-6 months (depending on treatment) | A panel of cytokines and adipokines |
| INF-gamma change | Time Frame: 4-6 months (depending on treatment) | Changes in IFN-γ levels after incubation with saline solution, TB antigen or phytohemagglutinin A Pre, during and post treatment |
| Changes in body composition | Time Frame: 4-6 months (depending on treatment) | Body composition pre and post treatment measured with DEXA-scanning and/or bioimpedance |
Countries
Denmark
Outcome results
None listed