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Diabetes and Tuberculosis – Old Associates Posing a Renewed Public Health Challenge
Growing Evidence of a Causal Relationship and increase the demand for insulin secretion. When the increased
There are several reports of high prevalence rates of diabetes in cases demand cannot be met (due to a pre-existing low β-cell mass), as is
of pulmonary TB (PTB) (4–20%), and rates are even higher for impaired often the case in poor TB patients with associated malnutrition, the
glucose tolerance test (16–29%).
10
A recent systematic review that potential underlying risk of diabetes may be unmasked.
identified 13 relevant observational studies found that diabetes is
associated with an increased risk of TB.
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Across the three cohort Regardless of the direction of the association, the common
studies analysed, the pooled relative risk of TB associated with diabetes–TB co-morbidity presents clinical challenges: first as a result
diabetes was 3.1 (95% confidence interval [CI] 2.27–4.26), and in the of stress-induced hyperglycaemia, second because rifampicin (one of
case-control studies the odds ratios of TB ranged from 1.16 to 7.83. the key drugs in any anti-TB regimen) may in itself have hyperglycaemic
The risks were higher in young people and in countries with a high effects and third because of the interaction between rifampicin and
background incidence of TB. Another systematic review reported several of the sulphonylurea group of oral hypoglycaemic agents,
similar findings, with relative risk estimates ranging from 1.5 to 7.8.
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including gliclazide, glyburide, glipizide and glimepiride, which are
In India, with an estimated 21 million adults with diabetes and 900,000 metabolised by CYP2C9, a liver enzyme induced by rifampicin. The
incident PTB cases in 2000, diabetes accounted for nearly 15% of PTB decreases in the area under the curve (AUC) for the various agents may
and 20% of smear-positive PTB.
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range from 22 to 70%
21
and require dose adjustment. Also important is
the fact that isoniazid (INH), another important and common drug used
The association is supported by the fact that diabetes patients have to treat TB, is prone to causing peripheral neuropathy, which may
evidence of impaired cell-mediated immunity, micronutrient worsen or mimic diabetic peripheral neuropathy; vitamin B
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deficiency, pulmonary microangiopathy and renal insufficiency, all of supplementation may be necessary. Pyrazinamide may interfere with
which predispose to PTB. Innate and type 1 cytokine responses are urine ketone testing. On theoretical grounds, it is also possible that
higher in TB patients with associated diabetes than in non-diabetes people with diabetes need a different TB treatment regimen due to
control subjects. The effect is consistently and significantly more higher risk of treatment failure.
marked in diabetes patients with chronic hyperglycaemia. The
impaired and altered immune response is also likely to increase Public Health and Clinical Implications
susceptibility to infection with multidrug-resistant (MDR) strains.
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The of the Apparent Association Between
association could also be the result of non-enzymatic glycosylation of Diabetes and Tuberculosis
tissue proteins inducing alteration in bronchocilliary functions, or Irrespective of whether the relation between diabetes and TB is causal
perhaps a result of diabetic autonomic neuropathy causing abnormal or caused by joint co-factors, in societies with relatively few resources
basal airway tone and consequent reduced bronchial reactivity and for healthcare and a double burden of non-communicable and
bronchodilation.
10
Although results are sometimes conflicting, several communicable diseases, management and control may benefit from
studies indicate that patients with TB who have diabetes present an integrated approach. How and to what extent can this be done?
with a higher bacillary load in sputum,
15,16
delayed mycobacterial
clearance
16,17
and higher rates of MDR infection.
18
Reviews of clinical Screening for Diabetes Among Tuberculosis Patients?
studies
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show that diabetes patients with TB often present with lower Should all TB patients be screened for diabetes? A clinical study in
lung infiltrates (similar to the radiographic pattern seen in patients Tanzania, with an already high threshold for recognising diabetes,
with HIV/AIDS) and more cavitary lesions and may have worse showed that unless an oral glucose tolerance test was performed at
treatment outcomes in terms of smear and culture conversion, case the start of therapy, over half of the cases with diabetes would have
fatality and treatment failure. Recurrence or reactivation of previously been missed.
22
In developing countries awareness of diabetes is
treated TB with the onset of diabetes has been reported. A study generally low, and because people with type 2 diabetes may have no
among TB patients in south Texas and adjacent north-east Mexico
19
or limited symptoms it is quite likely that poor and less educated
reported that people with diabetes (27.8% in Texas and 20.0% in patients will give no history suggestive of diabetes, particularly in the
Mexico) were no more likely to have a history of previous TB than presence of symptomatic TB.
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Screening for diabetes is thus the only
those without diabetes even after adjusting for age, gender and sure way to rule out concomitant disease. It may therefore be of value
alcohol and drug abuse. to screen TB patients for diabetes, but what is the most cost-effective
means of doing this? While we gather data to address these
A recent study
20
indicates that plasma levels of rifampicin may be questions, simple and economically realistic approaches can be
considerably (53%) lower in diabetes patients with TB compared immediately implemented at every TB clinic worldwide. These include
with patients without diabetes. Perhaps the metabolism of documenting self-reported diabetes in every new patient with TB and,
rifampicin is affected by diabetes, rendering it less effective and where feasible, performing a fingerstick glucometer assay for blood
predisposing to rifampicin resistance during treatment. Some glucose. Patients with high readings can then be flagged for potential
investigators have reported an association between severity of TB treatment failure and be accorded special attention.
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and abnormal glucose tolerance.
Screening for Tuberculosis Among Diabetes Patients?
Although the above data strongly suggest that diabetes is a causal risk Should every patient with diabetes be screened for latent TB
factor for TB, the evidence is not conclusive. Some risk factors may infection, at least in countries with a high TB burden? Current
predispose to both diabetes and TB, e.g. tobacco smoking and screening tests are challenging to use in resource-limited settings,
alcoholism. It is also possible that at least part of the reported and include the intradermal injection of tuberculin, which is read
association is reversed, i.e. that the risk of diabetes is increased among 48–72 hours later, or the more expensive interferon-gamma release
people with TB. The stress due to a chronic infectious disease, such as assays (IGRAs), which are costly and require specific laboratory
TB, that causes considerable catabolism may increase insulin resistance equipment. If these results are positive, how should the progression
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