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.
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
HbA1c
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.
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.
