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208 Diabetes Mellitus and Tuberculosis - Double Jeopardy

very strong, other studies have shown higher rates strated reduced interferon gamma and Interleukin-12
of reactivation of tuberculosis in diabetics. (3) expression in diabetic murine models with tuberculo-
sis. Innate immunity consisting of macrophages, that
3. Diabetes as a risk for active tuberculosis form the first line of defence against tuberculosis is
less effective in diabetics. This is due to the metabol-
The association of diabetes with tubercular disease
however is more worrisome. Several case control ic effects of hyperglycemia and advanced glycation
studies have pegged the relative odds of develop- end products. The oxidative stress that results from
ing tubercular disease in diabetic patients as ranging hyperglycemia weakens the phagocytic and killing
from 2.44 to 8.3 compared with non diabetics, mean- function of macrophages. Most adaptive immune
ing the chances of a diabetic acquiring tubercular response studies suggest that diabetes patients
disease is significantly higher than the non diabet- with TB have a hyper-reactive, but poorly effective
(4)
ic population. Long term follow up cohort studies cell-mediated response to mycobacterial antigens.
from Korea and South America have shown a high This provides indirect evidence of dysfunctional im-
incidence of tuberculosis amongst diabetics com- mune regulation of tuberculosis in diabetic patients.
pared to non diabetics, confirming this association. (5) This leads to inadequate clearing of the tubercular
(6) . Our Institute was part of a national level, multiple pathogen and in addition, also enhances the immune
centre study where we screened patients attending mediated injury in the human host. A genetic basis
diabetic clinics for active tuberculosis. Nearly 1.8 % of to this dysfunction has also been demonstrated.
that population had already identified active tuber- Reduced expressions of genes that regulate macro-
culosis or were newly diagnosed with tuberculosis. phage activity (Hexokinase 2, CD28) have been not-
Nearly 50% of these patients had sputum positive ed among diabetics, though the clinical significance
(8) (9)
pulmonary tuberculosis, meaning they were potential of the same is not entirely clear.
sources of infection to the community. This is a sig- 5. The influence of tuberculosis on diabetes mellitus
nificant number considering the diabetes burden in
our country. This study also describes protocols that Does tuberculosis affect diabetes mellitus? This is
can be followed to carry out a similar screening pro- a question that is worth answering, considering that
gramme in diabetic clinics. Such a screening program 10-30% of cases of tuberculosis have concurrent dia-
will serve both as a public health measure in iden- betes. Infections, including tuberculosis are known to
tifying sputum positive tuberculosis to limit spread worsen glycemic control. Some studies suggest that
and also achieve early diagnosis and treatment of tuberculosis can cause diabetes in patients without
(7)
patients with tuberculosis. results and challenges of prior evidence of the disease, by mechanisms that
screening patients with diabetes mellitus (DM are currently unclear. Others have demonstrated that
tuberculosis causes transient rise in blood glucose
Poor glycemic control among diabetics has been levels which revert to normal within 3 months of ini-
shown to have a higher association with the occur- tiation of therapy and continue to be normal atleast
rence of tuberculosis in a recent study of 4690 until 12 months after treatment. Long term follow up
elderly patients from Hong Kong . A Hba1c (glyco- studies are lacking. Many other workers have used
sylated haemoglobin) greater than 7% was found to oral glucose tolerance testing to show that tubercu-
represent a three times increased hazard for active losis patients have higher rates of glucose intoler-
tuberculosis compared to hba1c of less than 7%. (Haz- ance than do community controls. Whether the TB
ard ratio 3.11; 95% CI 1.63-5.92). This highlights that truly preceded the onset of diabetes or is this just
poor glycemic control rather than diabetes per se is better detection of pre existing diabetes is unclear.
a risk factor for tuberculosis. The clinical implication What therefore arises is the need to screen all pa-
of these findings suggest that every clinician must tients with a diagnosis of tuberculosis for glucose
consider diabetes mellitus as an important risk factor intolerance and to reiterate that TB infection per se
for active tuberculosis and therefore must invest in a may worsen glycemic control, thus needing initiation
diabetic screening. Glycemic control in diabetics with or titration of diabetic medications and suitable diet
tuberculosis should be an important goal of therapy. until tuberculosis is adequately treated.
(2)
6. Clinical presentation of Tuberculosis in
4. Biological plausibility for diabetes as a risk Diabetes:
for tuberculosis It is evident that diabetes mellitus affects the im-
Biologically the above risk has been explained on mune response to mycobacterial infections. Thus
multiple fronts. Animal model studies have demon- it is expected that the clinical presentation, extent

GCDC 2017