Journal of Clinical Tuberculosis and Other Mycobacterial Diseases 29 (2022) 100343

Contents lists available at ScienceDirect

Journal of Clinical Tuberculosis and Other

Mycobacterial Diseases
journal homepage: www.elsevier.com/locate/jctube

Tuberculosis and diabetes mellitus: Relating immune impact of

co-morbidity with challenges in disease management in high
burden countries
Uzair Abbas a, Kiran Iqbal Masood a, 1, Aalia Khan a, 1, Muhammad Irfan b, Nausheen Saifullah c,
Bushra Jamil b, Zahra Hasan a, *
a
Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan
b
Department of Medicine, The Aga Khan University, Karachi, Pakistan
c
Department of Chest Diseases, Jinnah Post-graduate Medical Centre, Karachi, Pakistan

A R T I C L E I N F O A B S T R A C T

Keywords: Mycobacterium tuberculosis (MTB) is the causative agent of TB. TB incidence is high in many low resource settings
Tuberculosis where limited health systems make it difficult for screening of co-morbid conditions. Susceptibility to TB is
Diabetes increased with coincident diabetes mellitus (DM) or prediabetes. DM leads to chronic, subclinical inflammation
Prediabetes
in the host leading to compromised protective immunity against MTB, impacting TB treatment. This review
Immunity
focuses on the immunological impact of DM and prediabetes on TB infections, highlighting the importance of
TB management
having effective diagnostic, treatment and management programs for early identification of hyperglycemia in TB
patients to improve treatment outcomes. Further, it describes challenges in monitoring of TB and DM co-
morbidity in a high-burden setting.

1. Introduction address the need for optimally managing DM in patients with TB.

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis 2. Burden of TB-DM in Asian countries
(MTB) that primarily affects the lungs. In 2020, TB caused an estimated
1.5 million deaths and an incidence of 10 million cases worldwide [1]. The WHO TB report for 2020 published on 14th October 2021,
TB has been on the rise since the 1980s, in part due to the HIV pandemic, identified TB as 13th leading cause of death worldwide, with estimated
growing multidrug resistance in MTB, and also increased numbers of 10 million new cases and 1.5 million deaths. Among the new cases re­
highly susceptible individuals such as, those with Type 2 Diabetes ported, 88 % were those from high TB burden countries among which
mellitus (DM) [2]. Currently, one-quarter of the population of the world India lead the count, followed by China, Indonesia, Philippines,
is latently infected with MTB [3]. Individuals with latent tuberculosis Pakistan, Nigeria, Bangladesh and South Africa [1]. The South Asian
infection (LTBI) are not infectious but may subsequently develop active region consists of eight low and middle-income nations, namely
TB due to reactivation of infection. This can occur as a consequence of Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and
granuloma liquefaction particularly in immune deficient or immuno­ Sri Lanka. They account for nearly 44 % of world TB cases and a high
compromised individuals, such as individuals with HIV or DM [4]. In­ burden of TB mortality (681,975deaths), 38 % of the worldwide burden
dividuals with DM and pre-diabetes (PDM) have been shown to suffer [5].
from chronic, sub-clinical inflammation that impacts effective immune The burden of cardio-metabolic diseases, particularly diabetes (DM)
function. Those with DM and PDM are more susceptible to TB infection has become a major health problem in South Asian countries, with an
than non-diabetics. Here we describe how DM- and PDM-related expected rise in prevalance of DM of more than 151 % between 2000
inflammation leads to increased susceptibility to TB. Further, here we and 2020 [6]. Moreover, population of this region is at higher risk of

Abbreviations: DM, type-2 diabetes mellitus; MTB, Mycobacterium tuberculosis; TB, tuberculosis.
* Corresponding author.
E-mail address: [email protected] (Z. Hasan).
1
These authors contributed equally.

https://doi.org/10.1016/j.jctube.2022.100343

Available online 29 November 2022

2405-5794/© 2022 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
U. Abbas et al. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases 29 (2022) 100343

developing DM as compared to other ethnic groups [7]. Prevalence of immune responses could be attributed to factors such as the elevated
DM in active TB cases is also on rise globally and especially, in South glucose concentration, leading to the production of Advanced Glycation
Asia since 2000 [8]. DM is found to escalate the risk of contracting TB by End products (AGE) and the constant inflammation, associated with DM.
three folds [9]. In 2009, the World Health Organization (WHO) and the DM is considered, by some, not solely a metabolic disease but a disease
International Union Against Tuberculosis and Lung Disease (IUATLD) of the immune system [26].
have recommended bi-directional TB-DM screening and integrated
management for both diseases in high burden countries [10]. 4. Inflammation in control of TB
A systemic review and meta-analysis of 74 studies (47 studies from
India, 10 from Pakistan, four from Nepal and two from both Bangladesh Inflammation is a protective host response aimed at defending
and Sri-Lanka), showed the pooled prevalence of DM in TB patients to be against invading pathogens. In response to MTB infection, an intricate
21 %, varying from 11 % in Bangladesh to 24 % in Sri-Lanka [11]. network of cytokines is established by cells of the innate and adaptive
Prevalence of DM in active TB cases is also on rise in South Asia since immune systems, directly or indirectly triggering anti-mycobacterial
2000 [8]. With an estimated 510000 new TB cases emerging each year, responses [27]. In the early phase of defence, cells such as alveolar
approximately 15,000 are reported to develop drug resistant TB every macrophage (AM), dendritic cells (DCs), neutrophils, monocytes and
year. Pakistan is ranked fifth among TB high-burden countries world­ natural killer (NK) cells secrete pro-inflammatory cytokines in order to
wide and it accounts for 61 % of the TB burden in the WHO Eastern attract additional leukocytes to the site of infection for further support
Mediterranean Region [12]. Pakistan has a high burden of DM as well as against MTB [28]. This is followed by the emergence of the adaptive
TB. Type 2 DM is 16.98 % prevalent [13]. Different studies have re­ immune response, driven largely by CD4+ and cytotoxic CD8+ T-lym­
ported a high rate of TB and DM co-morbidity in Pakistan. In one study, phocytes [29]. Together, these cell populations, each expressing distinct
it was found after screening of 211 TB patients, 11.4 % were diabetic pro- and/or anti-inflammatory cytokine profiles, elicit diverse cellular
while 21.3 % were found to be PDM [14]. A prospective cohort study on responses all directed towards restricting the growth of MTB and elim­
the prevalence of DM in pulmonary TB patients revealed 18 % of TB inating the reservoir of infection.
patients were diabetic and were more likely to have unfavorable out­ Of the pro-inflammatory cytokines, IFN-γ is absolutely crucial for the
comes as compared to non-diabetic pulmonary TB patients [15]. control of MTB. Secreted primarily by CD4+ and CD8+ lymphocytes, as
Through bi-directional screening, it was also found that 13.5 % of cases well as NK cells [30], it elicits a range of complex cellular responses to
with TB had newly diagnosed DM and 26.1 % were already known cases MTB from a variety of cell types. Its principle role is to activate the
of TB-DM, contributing to an overall 39.6 % prevalence of DM among TB innate bactericidal properties possessed by macrophage. TNF-α is
patients [16]. Diabetes was also found to cause more of multi-drug another powerful pro-inflammatory cytokine secreted primarily by
resistant tuberculosis (MDR-TB) as compared to non-diabetic Pakistani macrophage and Th1 (CD4+) cells, working synergistically with IFN-γ to
population [17]. boost intracellular killing of phagocytised mycobacteria [29]. Its role
extends to controlling the maintenance of the granuloma, rendering
3. The impact of diabetes and pre-diabetes on host immunity TNF-α critical for the containment of persistent TB.
Optimal functioning of the required defence responses are dependent
DM is a complex and multi factorial disease which is caused either by on the network and relative abundance of cytokines induced at varying
insufficient production of insulin or insulin resistance by the cells or stages of infection. Inadequate inflammation, through overexpression of
both [18]. DM is characterised primarily by (postprandial and post- anti-inflammatory cytokines or under-expression of pro-inflammatory
absorptive) hyperglycaemia, impaired secretion of insulin (by pancre­ cytokines, results in failure to clear infection and widely disseminated
atic β-cells); and insulin resistance. Insulin resistance, the failure of a disease [31,32]. For example, in the absence of IFN-γ, the intracellular
known quantity of insulin to stimulate the uptake of glucose in the body, environment of the macrophage remains at a neutral pH, with dimin­
can develop as a result of multiple factors such as, genetic abnormalities ished reactive radical production, and phagolysosomal fusion does not
in one or more proteins belonging to the insulin action cascade, foetal take place resulting in failure to kill intracellular MTB [33]. Diminished
malnutrition, and/or a rise in visceral adiposity [19]. In the context of quantities of TNF-α are associated with mortality, attributed in part to
insulin resistance, the liver is no longer able to suppress the release of the weakened anti-mycobacterial action of macrophage in addition to
glucose into the blood resulting in hyperglycaemia. Tissues in which impaired control of the granuloma [34]. Inhibition of TNF-α (reduced
insulin resistance typically occurs include the muscles, liver, and fat. inflammation) leads to acute, disseminated disease, and allows for
The global burden of DM was found to be close to 500 million in 2017, reactivation of LTBi in animal models [35]. The pro-inflammatory
with a predicted rise of 7079 per 100,000 population by 2030 [20]. cytokine profiles in TB patients is found to vary across the disease
PDM is a high-risk state for progression to DM. PDM have blood spectrum, increasing from minimal to severe disease for IFN-γ, CXCL9
glucose levels elevated above the normo-glycaemic range but main­ and other Type-1 cytokines [36]. However, although pro-inflammatory
tained below the threshold for DM. Unlike DM, PDM typically has no cytokines are intended to impart protection against MTB infection,
overt signs or symptoms other than impaired fasting glucose and/or excessive inflammation compromises the functionality of the innate and
impaired glucose tolerance [21]. The prevalence of PDM is on the rise adaptive immune systems and promotes immunopathology. Regulation
globally, it is estimated that over 470 million people will have PDM by of IFN-γ is required for MTB control and this is affected by suppressor of
2030 [22]. cytokine signalling (SOCS) 1 molecules which, are shown to be upre­
Uncontrolled DM can lead to alterations in the immune system, gulated in TB infections [37].
increasing the risk of susceptibility to infections including that with The interactions between the myriad of cytokines secreted during
MTB. Chronic sub-clinical inflammation is an important hallmark of DM different phases of infection, and how these cytokines influence the host
[23], and studies suggest that it is a component of the pre-diabetic state, cell and MTB have significant implications for the clinical outcome of
as well [24]. Inflammation plays an important role in the aetiology of infection (whether infection is cleared, remains latent or progresses to
DM, although the exact mechanisms through which it promotes patho­ active disease) [28]. It is crucial that levels of pro- and anti-
genesis are unclear. However, systemic, low-grade inflammation inflammatory cytokines are maintained at levels optimal for promot­
throughout the body is considered to be conducive to the development ing anti-mycobacterial action and minimising damage to host tissues.
of PDM and DM due to the ability of inflammation to induce organ
dysfunction [25], leading to hyperglycaemia and insulin resistance. It 5. Prediabetes and TB
remains unclear whether this inflammation always arises as a result of
hyperglycaemia and/or insulin resistance, or vice versa. Altered There have been a limited number of studies focusing on

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U. Abbas et al. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases 29 (2022) 100343

incorporating the analysis of subjects with PDM with regard to TB. High increased following exposure to MTB antigens in DM patients [51].
prevalence of PDM amongst those with, or at risk of, TB has also been Overall, these findings indicate an elevation of pro-inflammatory cyto­
reported in recent studies [38–39]. PDM is also independently associ­ kine levels as well as heightened Th1 and Th17 cell and cytokine re­
ated with active TB [40]. Due to certain shared characteristics (hyper­ sponses in TB-DM patients.
glycaemia and at times insulin resistance) between the two conditions, it MTB infection with diabetes can be rapidly progressive with a
has been speculated that DM and PDM may share similar pathologies shortened survival interval and more severe pulmonary and extra pul­
with regard to aberrant immune responses. The few studies on this topic monary pathologies [52]. The higher bacterial burden observed as
which have investigated the cytokine profiles of PDM-TB individuals compared to non-DM controls is associated with increased disease
presenting conflicting evidence. In one study, circulating levels of IFN-γ, severity, miliary TB, and higher bacterial load that contribute to
TNF-α and IL-2 (type 1), IL-17A and IL-17F (type 17), and IL-1β, IFNβ increased mortality rates of TB-DM patients [52].
and GM-CSF (pro-inflammatory) cytokines were found to be elevated in It has also been reported that patients with PTB and concomitant DM
TB-PDM individuals, as were systemic levels of the IL-5 (type 2), IL-10 were more likely to present with hemoptysis, positive acid-fast bacilli
and TGFβ (regulatory) cytokines. These findings suggest that PDM is (AFB) smear, cavity, higher erythrocyte sedimentation rate (ESR),
not associated with an imbalance of pro- and anti-inflammatory cyto­ higher serum C-reactive protein (CRP), lower serum albumin (ALB), or
kines but rather with their overall heightened expression in response to higher fasting blood glucose (FBG), as compared to non-diabetics [53].
active TB infection in comparison to TB patients without PDM [41]. In Individuals with TB and DM comorbidity have been shown to have
contrast, the presence of PDM in individuals with coincident LTBi (PDM- heightened levels of pro-inflammatory cytokines both prior to ATT, and
LTBi) was found to drastically reduce circulating plasma levels of IFN-γ, during the course of TB treatment [54]. This has clinical significance as
TNF-α, IL-2, IL-17F, and systemic levels of IL-1β, IL-18 (pro-inflamma­ excessive and prolonged inflammation results in increased morbidity
tory) and IL-10 (anti-inflammatory) at homeostasis, in comparison to and mortality in pulmonary TB largely, as a consequence of immune-
individuals with only LTBi in another recent study [42]. mediated lung damage [54].
Overall, aberrant functioning of the immune system in DM may pre-
6. Impact of tuberculosis and diabetes mellitus on host dispose DM patients to infectious diseases which require strong cell-
immunity mediated immune responses. Further studies are required to elucidate
the impact of diabetes-related inflammation on the immune response to
The function of neutrophils, macrophages, Natural Killer (NK) cells, MTB, and whether it exacerbates cellular responses that promote
and some other components of innate immunity is drastically compro­ immune-mediated pathology during the course of MTB infections.
mised by metabolic alterations in DM [43]. Alveolar macrophages have
a central role in hosts for MTB infection and replication, these macro­ 7. Impact of DM on treatment outcomes in TB
phages ingest the bacilli to enclose them in phagosomes and fuse with
lysosome along with digestion of the bacteria and production of anti­ DM has been observed to negatively influence treatment outcomes
microbial molecules like reactive nitrogen intermediates which leads to for patients with coincident TB. Uncontrolled DM either due to internal
formation of “granulomas,” which contain other immune effector cells, and external factors, worsens disease outcomes. This may be attributable
such as neutrophils and T cell [44]. to various factors, such as immune dysregulation in the form of impaired
Dysregulation of the immune system is a well-established feature of monocyte chemotaxis, diminished production of Th1-pattern cytokines
DM, characterised in part by impaired cytokine secretion [45]. DM is and nitric oxide [55] and elevated innate and type 1 cytokine expression
known to increase the risk of MTB infection in individuals, diabetics are [40]. The clinical presentation of TB is also more complex in patients
more susceptible to both developing active TB [46] or the reactivation of with DM. Patients present with more cavitary disease, higher severity
latent TB [47] in comparison to non-diabetics. and atypical sites like lower lobe predominance [56]. TB patients with
Alveolar macrophages from diabetic mice had increased the DM are found to have higher bacillary loads as compared to non-
expression of CCR2, which may restrain monocyte traffic to the lung, diabetics, resulting in more smear or culture positivity and a delayed
and reduced expression of CD14 and macrophage receptor which rec­ mycobacterial clearance [57]. Indicators for successful TB treatment are
ognizes the MTB cell wall components that contribute to reduced slowed down in patients with DM in comparison to non-diabetics such as
phagocytosis of MTB and increase tuberculosis susceptibility in diabetic sputum culture conversion. Several studies show that sputum culture
hosts [44]. conversion, from positive to negative, is delayed in DM patients [57].
Adaptive immunity against MTB infection is mostly cellular immune Research also shows that DM patients are at significantly higher risk of
responses [48]. T helper 1 (Th1) cells play a central role in the host relapse after completion of TB treatment [58]. Additional negative
defense by inducing the production of IFNγ, which potentiates the nitric treatment outcomes include slower improvement of pulmonary lesions
oxide- (NO-) dependent killing activity of macrophages, while IL-2 is an following treatment, higher likelihood of recurring infection, and
essential cytokine for the development and proliferation of Th1 and increased probability of treatment failure and death in DM patients [58].
CD8+ T cells, and Th17 cell secretes IL-17 and IL-23 that plays in­ TB with DM has also been associated with an increased risk of cardio­
flammatory response of TB [49]. vascular complications such as, myocardial infarction and stroke during
With regard to the immune response to TB in DM patients, data the early months of TB treatment in patients [59].
suggest that TB-DM is characterised by a pro-inflammatory milieu. One
study revealed that circulating levels of IFN-γ, TNF-α, IL-2 (type 1), IL-5 8. Factors affecting TB-DM treatment:
(type 2) and IL-17A (type 17) cytokines, as well as systemic levels of
additional pro-inflammatory cytokines such as IL-1B, IL-6 and IL-18, are TB treatments are the same in patients regardless of their diabetes
raised at baseline in patients with coincident DM and pulmonary TB status. However, as DM is associated with a slower treatment response,
[50]. Furthermore, plasma levels of type 1 and type 17 cytokines were increased drug resistance, treatment failures and relapsed TB, the
positively correlated with HbA1c levels of DM patients, suggesting that duration of ATT may need to be prolonged to prevent poor outcome. A
poor glycaemic control contributes to the pro-inflammatory environ­ study from Taiwan showed a lower relapse rate and better treatment
ment observed amongst DM patients [50]. Further work also describes outcomes with a nine-month as compared with a six-month treatment
heightened pro-inflammatory responses in TB-DM patients following regimen (hazard ratio 0.76; 95 % CI 0.59–0.97) [60]. A large meta-
exposure of whole-blood to MTB antigens, in comparison to TB patients analysis of 13 studies found a significant association between diabetes
without DM [50]. Frequencies of mono- and dual-functional (producing and MDR TB (OR 1.71, 95 % CI 1.32–2.22) [61]. In another meta-
one or two cytokines) (IFN-γ, TNF-α or IL-2) CD4+ Th1 cells are also analysis including 24 observational studies, a higher rates of MDR-TB

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U. Abbas et al. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases 29 (2022) 100343

(OR = 1.97, 95 % CI = 1.58–2.45) was found in diabetics, irrespective of diseases (TB-DM) was that of patients of sub continental and Asian
country income level [62]. Possible reasons of acquiring drug-resistance origin (55 %) [71]. Black and white populations were affected in almost
were higher initial bacterial load and slower response to treatment [63]. equal proportions (22 % and 23 %) with the conclusion that about one-
Drug susceptibility should be done in TB–DM patients both at baseline third of Asians with newly diagnosed TB will have DM [71].
and during follow-up to identify drug resistance and poor outcome.
Further, TB-DM patients may experience more side-effects and drug- 8.4. Gender and age
toxicity and drug interactions during TB treatment need a close
follow-up in these patients. Factors that impact DM and therefore A higher prevalence of TB and TB-DM in males as compared to fe­
treatment outcomes in TB are discussed below. males was shown in Brazil [72]. Globally,12 % of TB cases accounts for
children and adolescence [73]. A high prevalence of TB-DM comorbidity
8.1. Poor glycemic control in Asian countries, especially in China and India, may be a result of the
rapidly increasing prevalence of young-onset DM in these countries. In
Achieving optimum glycaemic control is important but can be very southern India, from 2000 to 2006, the prevalence of DM in people
difficult due to scarcity of adequate health care facilities, low educa­ younger than 44 years increased by 10.7 %. Data from China also
tional status, and economic disparities in TB patients. A 5-year survey, showed an 88 % increase in the prevalence of maturity-onset DM in the
documenting changes in diabetes practice in developing regions that 35–44 years age group, probably due to the rapid transition in dietary
included 11,799 patients showed that only 20–30 % of patients were at habits, reduced physical activity, longer working hours, and decreasing
the HbA1c <7 % goal [64]. Poor glycaemic control in Asian populations sleep hours. Although the data is very ambiguous, it has been shown that
represents a potentially important risk factor for TB. The Diabcare-Asia the relation between DM and TB is more prominent in younger people
project, a cross-sectional survey of 24,317 diabetic patients from [74] and this might be due to onset of diabetes in early age. However
Bangladesh, China, India, Indonesia, Malaysia, Pakistan, Philippines, some data suggest, sex, older age, poor glycemic control, having family
Singapore, South Korea, Sri Lanka, Taiwan, Thailand, and Vietnam, history of DM and TB illness are among the variables identified as
found that 55 % of patients had values of HbA1c exceeding 8 % [65]. A associated risk factors for TB-DM comorbidity [75]. A study reports
study showed that poor DM control (as indicated by HbA1c level) was higher lung damage in TB-DM as compared to TB alone in older popu­
associated with differences in the innate and cellular cytokine responses lation with a dominance of 50–60 years of age groups [76].
to stimulation with purified protein derivative from MTB, thus facili­
tating progression to active TB [66]. A study of 4,690 elderly diabetic 9. Challenges in screening for diabetes in TB patients.
patients in Hong Kong, showed that the patients with greater HbA1c
value (>7%) with a hazard risk of active TB that was 3 times increased Early identification of diabetes requires improvement at the level of
compared with those who had HbA1c <7 % (HR 3.11,95 % CI health systems. Often patients are unaware that they have raised gly­
1.63–5.92, p < 0.01) [67]. A cohort study with 123,546 individuals cemic levels. This has been demonstrated by reports from Pakistan
performed in Taiwan found that, during a median follow-up period of which showed that of newly diagnosed TB patients, 11.4 % patients had
4.6 years, diabetic patients with poor glycaemic control had a signifi­ diabetes and 21.3 % had prediabetes whilst further, 71 % of the di­
cantly higher hazard risk of TB (adjusted HR 2.21; 95 % CI 1.63–2.99, p abetics in the group studied did not know their hyperglycemic status
< 0.01) compared to those without DM [68]. The evidence of poor [77]. Health care providers in the private sector also need to be cogni­
glycaemic control in Asian patients, along with the fact that poor gly­ zant of underlying diabetes which may impact treatment outcome. Ac­
caemic control represents an important risk factor for TB, call for further cess to blood glucose testing is a limitation. Point of care glucometer
therapeutic actions in order to decrease TB-DM prevalence in devel­ testing needs to be available at TB screening centers. Further, upon
oping Asian countries. diagnosis of diabetes it is essential that patients are guided to diabetic
management services, counselling is required to guide patients
8.2. Insulin resistance regarding diet, lifestyle and also treatment that may need to be taken.
In systems where patients pay out of pocket, identification of dia­
Chao et al. investigated the immunological mechanisms underlying betes does not directly lead to immediate management of the conditions.
the susceptibility of diabetic patients to TB [69]. They measured the Medications are costly and may require multiple adjustments in dosage
level of resistin, a protein produced by immune cells in humans that and regimen to reach appropriate levels for individual cases. It is the
causes insulin resistance and inhibits reactive oxygen species (ROS) health-seeking behavior which needs to be modified in order to have a
production in leukocytes, and found that serum resistin levels were full impact on DM management generally and also in the context of TB-
significantly higher in patient groups with severe TB and DM when DM. Further, TB medications (especially rifampicin and isoniazid)
compared with mild TB cases and healthy controls. They hypothesized interact with those used to control blood sugars resulting in sub-optimal
that functional changes in macrophages seen in the state of insulin control of hyperglycemia [78] and underlying DM needs to be differ­
resistance may increase the risk for active TB [69]. entiated from treatment induced condition. Overall, it is a holistic
approach to TB and DM management that can benefit patients as neither
8.3. Genetic make-up condition can be treated separately.

Compared with European populations, Asians tend to develop dia­ 10. The way forward
betes at a younger age and at much higher incidence rates given the
same amount of weight gain. Genome-wide association studies (GWAS) Whilst TB and DM screening has been recommended by the World
have identified over 70 loci associated with DM. Although the majority Health Organization STOP TB initiatives as part of the End-TB strategy,
of GWAS results were conducted in populations of European ancestry, screening is not always practiced [79]. There need to be an increasing
recent GWAS in Asians have made important contributions to the awareness raising and implementation of DM screening and manage­
identification of DM susceptibility loci, which suggest the different ge­ ment at the level of National TB Control Programs. Efforts are underway
netic make up of Asian population in its diabetic patients [70]. through Universal Health Coverage (UHC) initiative. However, imple­
It is striking that even when they are not in their home countries, mentation of the programs and impact on outcomes need to be closely
people of Asian or Indian/sub continental origin show a higher preva­ monitored.
lence of DM in the presence of TB than the rest of the population. A study One option would be to integrate care of non-communicable diseases
comprising of four ethnicities found the group most affected from both (NCDs) like DM with common communicable diseases at primary

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U. Abbas et al. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases 29 (2022) 100343

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