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Diabetes and Tuberculosis—Old Associates Posing a Renewed Public Health Challenge
ignored and no significant initiative has been undertaken to jointly address due to a chronic infectious disease, such as TB, that causes considerable
this double burden. This neglect may have disastrous consequences. catabolism may increase insulin resistance and increase the demand for
insulin secretion. When the demand cannot be met (due to a pre-existing
Growing Evidence of a Causal Relationship low β-cell mass), as is often the case in poor TB patients with associated
There are several reports of high prevalence rates of diabetes in cases of malnutrition, the potential underlying risk for diabetes may be unmasked.
pulmonary TB (PTB) (4–20%), and rates are even higher for impaired
glucose tolerance test (16–29%).
10
A recent systematic review that Regardless of the direction of the association, the common diabetes–TB
identified 13 relevant observational studies found that diabetes is comorbidity presents clinical challenges: first as a result of stress-induced
associated with an increased risk for TB.
11
Across the three cohort studies hyperglycemia, second because rifampicin (one of the main drugs in
analyzed, the pooled relative risk for TB associated with diabetes was 3.1 any anti-TB regimen) may in itself have hyperglycemic effects, and third
(95% confidence interval [CI] 2.27–4.26), and in the case-control studies because of the interaction between rifampicin and several of the
the odds ratios of TB ranged from 1.16 to 7.83. The risks were higher in sulfonylurea group of oral hypoglycemic agents, including gliclazide,
young people and in countries with a high background incidence of TB. glyburide, glipizide, and glimepiride, which are metabolized by CYP2C9, a
Another systematic review reported similar findings, with relative risk liver enzyme induced by rifampicin. The decreases in the area under the
estimates ranging from 1.5 to 7.8.
12
In India, with an estimated 21 million curve (AUC) for the various agents may range from 22 to 70%
21
and require
adults with diabetes and 900,000 incident PTB cases in 2000, diabetes dose adjustment. Also important is the fact that isoniazid (INH), another
accounted for nearly 15% of PTB and 20% of smear-positive PTB.
13
important and common drug used to treat TB, is prone to causing
peripheral neuropathy, which may worsen or mimic diabetic peripheral
The association is supported by the fact that patients with diabetes neuropathy; vitamin B
6
supplementation may be necessary. Pyrazinamide
have evidence of impaired cell-mediated immunity, micronutrient may interfere with urine ketone testing. On theoretical grounds, it is also
deficiency, pulmonary microangiopathy, and renal insufficiency, all of which possible that people with diabetes need a different TB treatment regimen
predispose to PTB. Innate and type 1 cytokine responses are higher in TB due to higher risk for treatment failure.
patients with associated diabetes than in non-diabetes control subjects.
The effect is consistently and significantly more marked in patients with Public Health and Clinical Implications
diabetes with chronic hyperglycemia. The impaired and altered immune of the Apparent Association Between
response is also likely to increase susceptibility to infection with multidrug- Diabetes and Tuberculosis
resistant (MDR) strains.
14
The association could also be the result of non- Irrespective of whether the relation between diabetes and TB is causal or
enzymatic glycosylation of tissue proteins inducing alteration in caused by joint co-factors, in societies with relatively few healthcare
bronchocilliary functions, or perhaps a result of diabetic autonomic resources and a double burden of non-communicable and communicable
neuropathy causing abnormal basal airway tone and consequent reduced diseases, management and control may benefit from an integrated
bronchial reactivity and bronchodilation.
10
Although results are sometimes approach. How and to what extent can this be done?
conflicting, several studies indicate that patients with TB who have
diabetes present with a higher bacillary load in sputum,
15,16
delayed Screening for Diabetes Among Tuberculosis Patients?
mycobacterial clearance,
16,17
and higher rates of MDR infection.
18
Reviews Should all TB patients be screened for diabetes? A clinical study in
of clinical studies
13
show that patients with diabetes with TB often present Tanzania, with an already high threshold for recognizing diabetes, showed
with lower lung infiltrates (similar to the radiographic pattern seen in that unless an oral glucose tolerance test was performed at the start of
patients with HIV/AIDS) and more cavitary lesions and may have worse therapy, over half of the cases with diabetes would have been missed.
22
In
treatment outcomes in terms of smear and culture conversion, case developing countries awareness of diabetes is generally low, and because
fatality, and treatment failure. Recurrence or reactivation of previously people with type 2 diabetes may have no or limited symptoms it is quite
treated TB with the onset of diabetes has been reported. A study among likely that poor and less educated patients will give no history suggestive
TB patients in south Texas and adjacent north-east Mexico
19
reported that of diabetes, particularly in the presence of symptomatic TB.
23
Screening
people with diabetes (27.8% in Texas and 20.0% in Mexico) were no more for diabetes is thus the only sure way to rule out concomitant disease. It
likely to have a history of previous TB than those without diabetes even may therefore be of value to screen TB patients for diabetes, but what is
after adjusting for age, gender, and alcohol and drug abuse. the most cost-effective means of doing this? While we gather data to
address these questions, simple and economically realistic approaches
A recent study
20
indicates that plasma levels of rifampicin may be can be immediately implemented at every TB clinic worldwide. These
considerably (53%) lower in patients with diabetes with TB compared with include documenting self-reported diabetes in every new patient with TB
patients without diabetes. Perhaps the metabolism of rifampicin is affected and, where feasible, performing a fingerstick glucometer assay for blood
by diabetes, rendering it less effective and predisposing to rifampicin glucose. Patients with high readings can then be flagged for potential
resistance during treatment. Some investigators have reported an treatment failure and be accorded special attention.
24
association between severity of TB and abnormal glucose tolerance.
Although the above data strongly suggest that diabetes is a causal risk Screening for Tuberculosis Among
factor for TB, the evidence is not conclusive. Some risk factors may Patients with Diabetes?
predispose to both diabetes and TB, e.g. tobacco smoking and alcoholism. Should every patient with diabetes be screened for latent TB infection, at
It is also possible that at least part of the reported association is reversed, least in countries with a high TB burden? Current screening tests are
i.e. that the risk for diabetes is increased among people with TB. The stress challenging to use in resource-limited settings, and include the intradermal
US ENDOCRINOLOGY 13
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