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Why People With Diabetes Are at a High Risk of Tuberculosis

Why People With Diabetes Are at a High Risk of Tuberculosis

Posted By HealthcareOnTime Team Posted on 2021-08-14

Why having Tuberculosis with Sugar is dangerous?
TB with Diabetes is an Unhealthy Partnership. Tuberculosis and diabetes, one an age-old disease and the other steadily gaining prominence. One caused by a bacteria, the other by poor lifestyle habits and deviant immune activity. Where one is contagious, the other is chronic. Two diseases that may appear to have no apparent similarities except for their rise as worldwide epidemics. Yet, TB and diabetes have become unlikely partners, one promoting the development of the other, or both even joining up together to complicate situations that are already very serious.

Why People With Diabetes Are at a High Risk of Tuberculosis

TB with diabetes mellitus -a Deadly Linkage
The association between tuberculosis and diabetes is not a recent discovery, it was first described centuries ago by Persian philosophers. As per the WHO, 15% of global TB cases can be linked to diabetes.

Understanding the mechanism of these interactions and their dangers helps realize the seriousness of these two conditions and means to combat them. The significance of this link lies in the fact that they are both epidemics, with particularly high incidence rates in India; There are currently over 2,700,000 people in India who suffer from TB2 and around 69 million people suffering from diabetes (as of 2015). While a large number of cases of diabetes are lifestyle-induced, TB is an opportunistic disease which may remain latent in healthy individuals until they come down with other stressors, at which point, the TB becomes active again. Moreover, the partnership between TB and diabetes is two-sided. While diabetes promotes development of TB, a TB infection also increases the risk of developing diabetes by impairing glucose tolerance.

Diabetes-One half of a Dangerous Association The working of diabetes is well-known- it leads to elevated levels of sugar, which is the root of all problems associated with this disease. There is a reason that treatment of diabetes is focused on regulation of blood sugar. its harms are immense in number. It all begins with high levels of blood sugar damaging the elasticity of blood vessels, making them narrower. When blood supply does not reach different parts of the body, diseases associated with those parts begin to develop such as heart disease, kidney diseases and eye diseases. In addition, poor blood circulation in diabetes means immune cells are unable to reach pathogens and remove them effectively. This causes high susceptibility in these individuals for developing infectious diseases, including tuberculosis.

TB-the Other Half With the rise of urbanization and obesity, the number of diabetes cases is expected to rise further, and along with it, the TB incidence may also increase. It is estimated that diabetes mellitus (DM) increases the risk of TB by 3 times and the number of people with TB-DM comorbidity now surpasses the number of TB-HIV co-infection cases. This is because, while DM increases the risk of TB only 3 times as compared to 20 times by HIV, TB endemic regions such as India have a great number of people with TB. This causes the TB-DM comorbid patients to outnumber even those with TB-HIV. It is difficult to know exactly which of these disorders leads to the other, however in most cases, data shows that DM paves the way for TB, with poor blood sugar control being the risk factor for a TB infection rather that DM itself. Thus, people who have diabetes mellitus should be warned about their higher likelihood of contracting a TB infection.

What is Clinical Presentation of Patients with TB-DM?
Considering that DM occurs in a wide variety of demographics with respect to age, glucose control level, type of complication and treatment medications used studying DM as a risk factor for TB is complex. It has been found that clinical manifestation among patients with TB-DM are more severe. The incidence of TB-DM comorbidity is more common in regions with high prevalence of TB. Patients with TB-diabetes mellitus comorbidity are different from those from TB alone: they are more likely to be obese and older. In contrast, people with TB who later developed diabetes are more often males, younger and have lower HbA1c. Identification of DM in TB patients early is thus possible and essential, in order to avoid additional and irreversible damages associated with DM such as vascular complications. Clinical and radiological manifestations are more severe among patients with diabetes mellitus and TB. The radiographic presentation of TB depends on many factors, including duration of illness and host immune status. A large number of TB-DM patients show lower-lung involvement while those without DM show upper-lobe Cavity in Upper-lobe involvement. This finding can help prevent TB-DM being misdiagnosed as community acquired pneumonia or cancer. Patients with TB-DM are more likely to present with pulmonary form of TB, as well as cavitary and sputum-smear positive TB at the time of diagnosis, These individuals also take longer to convert from sputum-positive to sputum-negative status. Further, drugi resistance of TB is also more commonly reported in TB., DM patients, as per some studies. With loss in TB-DM patients is more frequent that in non-DM TB patients,

Why is diabetes a risk factor for tuberculosis?
Evidence is emerging that TB-diabetes is positively associated to adverse TB treatment outcomes, such as delay in microbial clearance, treatment failure, relapse, re infection as well as death. In patients with no history of TB, an exposure to MTB bacteria from an infected individual leads to no infection in 70% of the cases. Among those who are infected, the risk of reactivation is only 10%. However, those who suffer from poorly controlled diabetes, the likelihood of suffering from TB increases and presumably cured individuals have higher risk of relapse. DM also increases the risk of MTB reinfection in patients who have previously suffered from TB, patients with DM are more likely to have infections caused by the same bacteria as the previous episode, Although some reports suggest that DM is a risk factor in conversion of latent tuberculosis to active TB disease the relative risk of primary reactivation against reactivation due to DM has not been investigated so far. Despite this, indirect evidence suggests that not only does DM facilitates reactivation of TB, it also increases the risk of latent TB in close contacts. In many cases, TB patients do not realize that they have DM. The poorer outcome in patients with TB who also suffer from diabetes is linked to poor glycemic control. Chronic glycemia impairs immune activity against MTB in patients with DM, thereby also reducing the efficiency of anti-microbial treatment. Macrophages, a kind of immune cells, are the most adversely affected by DMinduced hyperglycemia with even short surges of high blood glucose capable of severely depressing their activity. This is associated with elevated levels of HbA1c and higher mortality. Further, high blood glucose negatively affects the small blood vessels present within the lungs leading to decreased lung tissue perfusion which normally allows healthy immune surveillance. A second reason could be the sub-optimal concentration of anti-mycobacterial drugs in the plasma of DM patients as compared to non-DM TB patients. Not only could this lead to treatment failure, but also contribute to development of drug resistance in MTB.'

Though the physiopathology of the coexistence of these two diseases is little understood, changes to the immune system of patients with active TB and DM have been described. These include:
Reduced activation of alveolar macrophages
Reduction in the capacity to produce interleukin-10,
Reductions in Th1 cytokines and
Alterations in the innate response
The risk of TB is higher in type 1 diabetes than type 2 since these individuals tend to be younger, have lower body weight and poorer glycemic control."

How does TB affect diabetes?
The incidence of diabetes appears to be higher among tuberculosis patients than the general population. Studies have reported 12%-44% of TB cases linked with DM at the time of TB diagnosis." In severe tuberculosis, functioning of the pancreas is adversely affected. Such patients have a higher incidence of chronic calcific pancreatitis, leading to insulin deficiency. In many TB cases, patients without prior history of DM suffer from glucose intolerance. TB infection purportedly impairs glycemic control and reduces the effectiveness of DM management.

Immune activity against MTB in DM patients is dysfunctional, with either excessive or delayed response against the bacteria. In case of latent tuberculosis, it is possible that lower levels of pro-inflammatory cytokines due DM can lead to progression to active TB disease. In contrast, people with active TB-DM show hyperinflammatory response to MTB. Elimination of MTB by antibiotics requires cooperation between innate and adaptive immune responses. The fact that there is higher incidences of adverse outcomes in DM patients indicates that hyper-reactive immune response in TB DM patients is not effective in killing MTB.

Screening and Diagnosis of TB-Diabetes
The tests used to diagnose latent TB include interferon gamma release assay (CRA) which is based on immunological memory of MTB. Since immunity as dysfunctional due to DM, the possibility that the result of this test is compromised has been investigated. It has been found the IGRA, including QuantiFERON-TB Gold assays by Qiagen and T.Spot-TB, can both be used reliably for diagnosis of latent TB in patients with DM. Performing chest x-rays at the time of DM diagnosis has been suggested for latent TB screening.

Many patients with TB, diabetes is often unrecognized. Screening for DM in patients with TB could improve case detection, early treatment, and prevention of DM complications. Some of the tests that can be used include
Fasting Blood Glucose (FBG)
Random Blood Glucose (RBG)
2 hour Postprandial Glucose (2hPG)
urine Glucose

How is diabetes treated in tuberculosis?
Diabetes patients with TB reportedly require higher doses of insulin, as compared when they did not have TB.6 On the other hand, an overdose of anti-TB medications such as isoniazid may cause hyperglycemia by accelerating the metabolism of sulphonylureas and biguanides, making diabetes more difficult to manage. Anti-TB medications may also interact negatively with medications for diabetes, and adverse drug reactions are more common in TB patients with DM. For instance, isoniazid decreases the metabolism of oral antiglycemic agents and increases their plasma levels. These complex interactions necessitate awareness about the possibility of DM in clinicians treating TB in TB-DM patients.

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How do you manage a patient with TB and diabetes?
Based on the information available on TB-diabetes, certain guidelines have been formulated specifically for DM patients who suffer from TB. Patients with TB over the age of 45, those who have high BMI, family history of diabetes, are recommended to undergo screening tests for DM. In addition, patients with DM while being treated for TB should be given vitamin B6 along with anti-TB medications due to their higher risk nerve damage from DM. Lastly, therapeutic drug monitoring is recommended to make sure the patient is receiving adequate dose of the medication and tailor the treatment accordingly. This is particularly so in case of patients with end stage renal disease who are undergoing dialysis. Patients with preexisting diabetes who are being treated with oral agents may be switched to insulin therapy in active TB once diagnosis is made.

It is essential for patients with DM to recognize that they are at high risk of contracting TB. Similarly, patients who suffer from TB may also be unwittingly suffering from early non-symptomatic stage of DM. Thus, awareness about this association is necessary for both the patient and clinicians so appropriate screening procedures may be implemented to reduce the burden of both these epidemics.

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