Diabetes screen during tuberculosis contact investigations highlights opportunity for new diabetes diagnosis and reveals metabolic differences between ethnic groups

Restrepo, Blanca I.; Kleynhans, Léanie; Salinas, Alejandra; Abdelbary, Bassent; Tshivhula, Happy; Aguillón-Durán, Génesis P.; Kunsevi-Kilola, Carine; Salinas, Gloria; Stanley, Kim; Malherbe, Stephanus T.; Maasdorp, Elizna; García, Juan Ignacio; Louw, I.; García-Oropesa, Esperanza Milagros; López-Alvarenga, Juan Carlos; Prins, John; Walzl, Gerhard; Schlesinger, Larry S.; Ronacher, Katharina

doi:10.1016/j.tube.2018.08.007

Cited by 20 publications

(26 citation statements)

References 39 publications

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“…These findings are in line with the immune response alterations noted in humans and in animal models of TB-DM [18,39,40,44,45]. However, the additional contribution to TB risk conferred by autoimmune or metabolic abnormalities in type 1 or type 2 DM, respectively, cannot be ruled out [43,46].…”

Section: Association Between Tb and Dm By Dm Severity And Chronicitysupporting

confidence: 68%

“…However, as indicated in this older literature, the cause of death may not necessarily be TB, but rather, DM complications such as cardiovascular diseases [17,46,49]. Today there is also evidence for other adverse outcomes in TB-DM patients (versus TB-no DM), such as delayed clearance of M. tuberculosis during the course of treatment based on AFB smears or cultures, but these protocols were not established in the early 20 th century [50].…”

Section: Is the Association Between Tb And Dm Bi-directional?-banyaimentioning

confidence: 99%

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The re-emerging association between tuberculosis and diabetes: Lessons from past centuries

Cadena

Rathinavelu²,

López-Alvarenga

et al. 2019

Tuberculosis

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The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20 th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we evaluate unique aspects of this comorbidity in older times, such as the frequent diabetic comas that suggest challenges for proper DM management as insulin was being implemented, or the absence of antibiotics to cure TB. Despite the unique aspects of each study period, the literature across times is consistent in key aspects of the association. Namely, a higher TB prevalence among DM (versus non-DM patients), the importance of glucose control and chronic DM on TB susceptibility and the higher risk of death among patients with the comorbidity. From the older literature, we can infer the likely contribution of type 1 DM to TB (in addition to type 2), regardless of their differing autoimmune or metabolic pathophysiology, respectively. Furthermore, in the older literature there was a notable reporting of DM development among TB patients, even though DM usually preceded TB. This observation deserves further epidemiological and basic studies to elucidate this intriguing aspect of the relationship between TB and DM.

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Section: Association Between Tb and Dm By Dm Severity And Chronicitysupporting

confidence: 68%

Section: Is the Association Between Tb And Dm Bi-directional?-banyaimentioning

confidence: 99%

The re-emerging association between tuberculosis and diabetes: Lessons from past centuries

Cadena

Rathinavelu²,

López-Alvarenga

et al. 2019

Tuberculosis

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“…Third, it has been suggested that the higher death in TB-DM patients is not due to TB, but to DM complications such as cardiovascular diseases [49, 50]. Accordingly, in a recent principal component analysis we found that cardiovascular risk factors (low density cholesterol, triglycerides and central obesity) were correlated with factors defining DM (haemoglobin A1c (HbA1c) and insulin resistance) in participants from South Africa, but not in Mexican Hispanics [51]. Finally, in our study a proportion of the TB patients (4.7%) were not followed when they defaulted treatment, and we were not able to assess other poor outcomes such as TB recurrences and relapses, which are reportedly associated with DM [13, 52].…”

Section: Discussionmentioning

confidence: 99%

Diabetes, undernutrition, migration and indigenous communities: tuberculosis in Chiapas, Mexico

Rashak¹,

Sánchez-Pérez

Abdelbary

et al. 2019

Epidemiol. Infect.

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We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41–64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.

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“…Such animal models mimic clinical observations from individuals with TB and diabetes co-morbidity and are particularly useful to study immune responses at the site of infection, the lung, which is difficult to achieve in patients. Given the high global prevalence rates of pre-diabetes in TB household contacts from both low and high TB burden countries -with 23% and 25% in South Africa and South Texas, respectively (Restrepo et al, 2018) -it is imperative to expand TB and diabetes association studies to include pre-diabetes. No animal models of pre-diabetes and TB have been described to date.…”

Section: Introductionmentioning

confidence: 99%

Pre-diabetes increases tuberculosis disease severity, while high body fat without impaired glucose tolerance is protective

Sinha

Ngo

Bartlett

et al. 2021

Preprint

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Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerance vs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection with M. tuberculosis (Mtb) H37Rv after the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-α, IFN-γ, IFN-β, IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association.

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Diabetes screen during tuberculosis contact investigations highlights opportunity for new diabetes diagnosis and reveals metabolic differences between ethnic groups

Cited by 20 publications

References 39 publications

The re-emerging association between tuberculosis and diabetes: Lessons from past centuries

The re-emerging association between tuberculosis and diabetes: Lessons from past centuries

Diabetes, undernutrition, migration and indigenous communities: tuberculosis in Chiapas, Mexico

Pre-diabetes increases tuberculosis disease severity, while high body fat without impaired glucose tolerance is protective

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