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    The Challenge of Tuberculosis and Diabetes Mellitus Comorbidity

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    Hendra Aryawinata
    The document discusses the challenges of tuberculosis (TB) and diabetes mellitus (DM) comorbidity. It notes that 15% of TB patients also have DM, and TB-DM is associated with poorer treatment outcomes. However, little is known about the underlying reasons for this. The document outlines objectives and methodology to better understand screening and management of TB-DM, as well as the cellular and molecular mechanisms influencing susceptibility and treatment outcomes. A pragmatic trial will evaluate the impact of enhanced DM monitoring on clinical and microbiological TB treatment outcomes.

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    The Challenge of Tuberculosis and Diabetes Mellitus Comorbidity

    Uploaded by

    Hendra Aryawinata
    34 views23 pages
    The document discusses the challenges of tuberculosis (TB) and diabetes mellitus (DM) comorbidity. It notes that 15% of TB patients also have DM, and TB-DM is associated with poorer treatment outcomes. However, little is known about the underlying reasons for this. The document outlines objectives and methodology to better understand screening and management of TB-DM, as well as the cellular and molecular mechanisms influencing susceptibility and treatment outcomes. A pragmatic trial will evaluate the impact of enhanced DM monitoring on clinical and microbiological TB treatment outcomes.

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    The document discusses the challenges of tuberculosis (TB) and diabetes mellitus (DM) comorbidity. It notes that 15% of TB patients also have DM, and TB-DM is associated with poorer treatment outcomes. However, little is known about the underlying reasons for this. The document outlines objectives and methodology to better understand screening and management of TB-DM, as well as the cellular and molecular mechanisms influencing susceptibility and treatment outcomes. A pragmatic trial will evaluate the impact of enhanced DM monitoring on clinical and microbiological TB treatment outcomes.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    34 views23 pages

    The Challenge of Tuberculosis and Diabetes Mellitus Comorbidity

    Uploaded by

    Hendra Aryawinata
    The document discusses the challenges of tuberculosis (TB) and diabetes mellitus (DM) comorbidity. It notes that 15% of TB patients also have DM, and TB-DM is associated with poorer treatment outcomes. However, little is known about the underlying reasons for this. The document outlines objectives and methodology to better understand screening and management of TB-DM, as well as the cellular and molecular mechanisms influencing susceptibility and treatment outcomes. A pragmatic trial will evaluate the impact of enhanced DM monitoring on clinical and microbiological TB treatment outcomes.

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    Concurrent Tuberculosis and Diabetes Mellitus

    Unraveling the causal link, and improving care

    The challenge of tuberculosis and


    diabetes mellitus comorbidity
    Hazel M Dockrell
    London School of Hygiene & Tropical Medicine
    TB and diabetes- getting better or worse?

    • We hope that we may be able control TB- but things


    do not look good for diabetes which is increasing
    worldwide
    • The number of people with diabetes rose from 153
    million in 1980 to 347 million in 2008 and is expected
    to rise to 592 million by 2035
    • 80% of those with diabetes currently live in low or
    middle income countries, where there is a lot of
    tuberculosis
    • Does co-morbidity with TB and diabetes matter?

    18.03.2015 2
    Diabetes can increase the risk of tuberculosis
    3-fold, and many TB patients have diabetes

    The Indian State of Kerala


    has reported that 44% of
    its TB patients have
    diabetes – another study
    by Nandakumar et al
    (PlosOne 2013) found
    24% of the TB patients
    had type 2 DM
    Morbidity for hypertension, HIV, Type 2 diabetes and TB in
    Khayelitsha, Cape Town
    ( based on prescriptions given to 32,474 patients over 9 months)

    18.03.2015
    Oni4 et al, BMC Infect Dis , 2015
    Projected diabetes changes from 2010-2030
    data from WHO and International Diabetes Association (Lancet Infect Dis 2009, 9:737)

    18.03.2015 5
    The impact of diabetes on tuberculosis infection

    Hodgson et al, Immunology 2014, 144:171


    12.03.2013 6
    WHO and the International Union against Tuberculosis
    and Lung Diseases Collaborative Framework

    12.03.2013 7
    Concurrent Tuberculosis and Diabetes Mellitus
    Unraveling the causal link, and improving care
    Concurrent Tuberculosis and Diabetes Mellitus
    Unraveling the causal link, and improving care
    What needs to be done?

    The Facts… Questions…


    • 15% TB also with DM 1. How to screen?

    • TB-DM: Poor outcome 2. How to manage?

    • Little is known about why worse 3. What is the basis for the poor
    outcome of TB in DM outcome?

    • Even less known about basic 4. What is basic mechanism for


    mechanism for susceptibility susceptibility?

    6/3/2015
    10
    Objectives:

    1. Feasible, accurate & cost-effective ways of screening TB DM

    2. DM management during and after TB treatment


    • effect of glucose control on TB treatment outcome.

    3. Pathways that enhance susceptibility to, and poorer treatment


    outcomes of TB-DM

    4. Cellular & molecular basis for the causal link between DM & TB
    • the effect of hyperglycemia and genetic variation on the host protective
    response to Mtb.

    6/3/2015 11
    Central hypotheses:

    1. Screening and management of DM among TB patients can be


    greatly improved and simplified with a major impact on control of
    TB-DM co-morbidity.

    2. The effect of DM on TB susceptibility and outcome is regulated,


    at least partly, by hyperglycemia, which dysregulates the cellular
    response to M. tuberculosis (Mtb), and by genetic variation
    common to both diseases

    6/3/2015 12
    Methodology

    2000 2000

    350

    6/3/2015 13
    Screening TB patients for DM and DM
    patients for TB
    All newly diagnosed TB patients (N=2000)
    • history of DM
    • HbA1c (gold standard)
    • POC HbA1c, rcg, fpg, urine dipstick, diabetes risk score
    (alone/combination)

    Feasibility, accuracy, and cost of those modalities

    Previously known DM patients (N=2000)


    •Symptom screen
    •CXR
    •and followed by sputum examination

    •Most DM identified in TB patients is pre-existing not newly diagnosed DM


    6/3/2015 14
    Screening diabetes patients for active and
    latent TB…
    Data from 4 sites (n: 807 )
    • History of TB: 6.4 – 25.5%
    • Very low prevalence of active TB
    • …

    Data from Indonesia (n: 375)


    • IGRA test
    • Prevalence: 38%
    • …

    Ruslami/TANDEM consortium, unpub. data

    6/3/2015 15
    Pragmatic trial in TANDEM

    • Objective:
    • To evaluate the effect of enhanced glycemic monitoring of DM during TB
    treatment on clinical & microbiological outcomes.

    • Study design:
    • 350 TB-DM patients across the sites (Romania, Peru and Indonesia)
    • Randomization for the clinical monitoring strategies
    • Normal practice (standard)
    • More intensive monitoring (intensive)

    6/3/2015 16
    Gene expression changes occurring during tuberculosis
    treatment: will these be different in TB-DM?
    hybridization intensity
    Average normalized

    4,151 gene
    entities >2-fold
    between time-
    points, P<0.05
    Diagnosis Week 1 Week 2 Week 4 Week 26

    Patients after 1 week of


    Patients at diagnosis treatment Treatment duration
    4 weeks 26 weeks
    Early changing gene entities

    •Marked changes in gene expression (Affymetrix) early and late during


    treatment (Cliff et al J Infect. Dis, 20123, 207:18)
    Diabetes affects different tissues and cells….

    For example, can


    Mtb infect
    adipocytes?

    12.03.2013 18
    Hodgson et al, Immunology 2014, 144:171
    Immune mechanisms that might contribute to the
    greater susceptibility of diabetes patients to Mtb

    12.03.2013 19
    Hodgson et al, Immunology 2014, 144:171
    T cell and macrophages interactions in TB: Impact of
    type 2 diabetes mellitus and HIV

    Ronacher, Joosten, van Crevel, Dockrell, Walzl, Ottenhoff Immunological


    12.03.2013 Reviews 2015, 264: 121–137 20
    Effect of hyperglycaemia on macrophages infected with M.tb

    M0 M2

    M2 M2

    12.03.2013 Lachmandas
    21 et al PloS One 2015
    Comorbidity with TB and diabetes does matter:

    • Patients with type 2 diabetes mellitus have a 3-fold


    increased risk of developing TB
    • Diabetes may alter the clinical presentation of
    tuberculosis
    • Diabetes may make TB harder to treat successfully
    • Diabetes may increase the rates of TB relapse following
    apparently successful treatment
    • Hopefully our ongoing studies will help identify the most
    effective ways of bidirectional screening, of managing TB-
    DM patients and bring greater insights into the
    mechanisms underlying these interactions

    18.03.2015 22
    Thank you…

    TANDEM: Tuberculosis and Diabetes Mellitus


    www.tandem-fp7.eu

    6/3/2015 23

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