Case Reports

Remission of Tuberculosis Following Control of Glycemic

Excursions in a Patient with Type 2 Diabetes Mellitus:
A Case Report
Anand Hinduja
Consultant Physician, Aarti Clinic, Navi Mumbai, Maharashtra, India

Abstract
Rationale: Tuberculosis (TB) and diabetes mellitus (DM) are converging epidemics, each worsening the morbidity of the other. Chronic
hyperglycemia is associated with dysfunctional immunity to Mycobacterium in patients with DM and, therefore, is likely to decrease
the efficiency of anti-mycobacterial treatment. Early aggressive management of TB and timely initiation of insulin therapy helps in
controlling the glycemic excursions that are otherwise not controlled by multiple oral antidiabetic agents. Patient Concerns: A 42-year-
old female with type 2 diabetes for six years presented with complaints of persistent cough, pain in the chest, weight loss, and loss of
appetite for two months in November 2018. Diagnosis: The patient was diagnosed with multidrug-resistant TB (MDR-TB), which
further progressed to extensively drug-resistant TB (XDR-TB) in February 2019. Her hemoglobin A1c (HbA1c), which was 8.3%
prior to TB diagnosis, increased to 13.8%. Interventions: The patient was initiated on anti-TB medications as per the Revised National
TB Control Programme (RNTCP) guidelines. The antidiabetic regimen consisted of glimepiride 2 mg b.i.d, metformin 500 mg b.i.d,
and voglibose 0.2 mg b.i.d. On confirmation of XDR-TB and persistently high HbA1c, insulin glargine was initiated in July 2019.
Due to continued uncontrolled blood glucose levels, insulin IDegAsp (30% Aspart and 70% Degludec) was initiated in February 2020.
Results: After the initiation of IdegAsp, HbA1c levels reduced significantly and there was improvement in the measures of daily blood
glucose level indices such as time in target range (TIR), time below target range (TBR), and time above target range (TAR). Optimal
blood glucose was achieved in a significant amount of time in a day. Sputum was negative for XDR-TB in February 2021, and the
patient recovered from TB. Her HbA1c was reported to be 7.5% in February 2021. Conclusion: In patients with type 2 diabetes and TB,
maintaining optimal blood glucose level for a longer duration of time can have a positive impact on host immunity and also enhance
the effect of ATT and better outcomes of TB infection. This case study highlights the importance of good glycemic control in patients
with type 2 diabetes who acquire TB infection.

Keywords: Diabetes mellitus, extensively drug-resistant tuberculosis, glargine, glycemic variability, IDegAsp, tuberculosis

Introduction or without resistance to other first-line anti-TB drugs

is considered to be suffering from MDR-TB. Patients
TB remains the foremost contributor to the burden
with MDR-TB may have additional resistance to any/
of infectious disease worldwide. In 2019, about 10
all FQ (fluoroquinolones) or any other anti-TB drug.
million people globally developed TB and 1.4 million
XDR-TB is caused by Mycobacterium tuberculosis
died; geographically, 44% of the cases were in the
strains that fulfil the definition of multidrug-/rifampicin-
World Health Organization (WHO) regions of South-
resistant TB (MDR/RR-TB) and are also resistant to
East Asia.[1] India is among the 30 high TB burden
countries. A  patient with TB whose biological specimen
is resistant to both H(isoniazid) and R(rifampicin) with Address for correspondence: Dr. Anand Hinduja,
Consultant Physician, Aarti Clinic, Navi Mumbai, Maharashtra, India.
Received: 21-July-2021, Revised: 16-September-2021, Accepted: 25-October-2021, E-mail: dranand01@gmail.com
Published: 31-March-2022
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DOI: How to cite this article: Hinduja A. Remission of Tuberculosis

10.4103/jod.jod_96_21 Following Control of Glycemic Excursions in a Patient with Type 2
Diabetes Mellitus: A Case Report. J Diabetol 2022;13:133-7.

      © 2022 Journal of Diabetology | Published by Wolters Kluwer ‑ Medknow 133  

 Hinduja: Remission of tuberculosis following control of glycemic excursions
any fluoroquinolone (levofloxacin or moxifloxacin) and
at least one additional Group A drug (presently to either
bedaquiline or linezolid or to both).[2]
Diabetes is one of the determinants of TB, and it triples
the risk of developing TB. Moreover, poor glycemic
control adversely affects TB treatment outcomes with
effects such as prolongation of culture conversion,
treatment failure, relapse, and death.[1,3] TB and DM are
converging epidemics, with each worsening the morbidity
of the other.[4]
According to a study conducted in Taiwan, a significantly
higher hazard of TB (hazard ratio of 2.21) was reported
in patients with DM having poor glycemic control (fasting
plasma glucose [FPG] >130 mg/dL) compared with those
without DM. This study also showed that the hazard of
TB in patients with diabetes with good glycemic control
(FPG <130 mg/dL) did not differ significantly from that
in individuals without DM.[5] Chronic hyperglycemia is
associated with dysfunctional immunity to Mycobacterium
in patients with DM and, therefore, is likely to decrease the
efficiency of anti-mycobacterial treatment. Hyperglycemia
may also compromise Mycobacterium killing by affecting
the microvasculature and reducing lung tissue perfusion
for optimal immune surveillance.[6] Conversely, anti-TB
drugs can worsen glycemic control in multiple pathways.[7]
Here, I  report a case of a patient with type 2 diabetes
who further developed XDR-TB and was managed on
IDegAsp along with oral antidiabetic drugs.
Case Report
Patient information
A 42-year-old female with type 2 diabetes for six years
presented with complaints of persistent cough, pain
in the chest, weight loss, and loss of appetite for two
months in November 2018. The patient was diagnosed
with MDR-TB, which further progressed to XDR-TB in
February 2019. Her HbA1c, which was 8.3% prior to TB
diagnosis, increased to 13.8%. The patient was initiated on
anti-TB medications as per the RNTCP guidelines. The
antidiabetic regimen consisted of glimepiride 2 mg b.i.d,
metformin 500 mg b.i.d, and voglibose 0.2 mg b.i.d. The
patient presented to our outpatient clinic as the blood
sugar levels remained uncontrolled with the previous drug
regimen.
Clinical findings and diagnostic assessments
On examination, her blood pressure was 125/85  mmHg,
weight was 59 kg, height was 165 cm, and body mass
index was 21.7 kg/m2. On further investigations, HbA1c
was noted as 13.8%; other parameters, including blood
cholesterol, liver function test, and serum creatinine, were
normal; urine ketones were absent; and serum osmolality
was normal. Also, she did not have any prior hypertension
or dyslipidemia. However, she complained of tingling
134 134  Journal of Diabetology ¦ Volume 13 ¦ Issue 1 ¦ January-March 2022
and a burning sensation in her feet and was diagnosed
with distal symmetric polyneuropathy secondary to
uncontrolled diabetes.
Therapeutic intervention
As the glucose levels were not controlled even with multiple
oral hypoglycemic agents (OHAs), insulin glargine (10
units at bedtime) was initiated along with the addition of
pioglitazone (15 mg twice a day). Sulfonylureas and alpha-
glucosidase inhibitors were discontinued considering
the initiation of insulins and to avoid hypoglycemia.
Metformin 500 mg was continued twice a day. The dose of
glargine was up-titrated to 24 units at bedtime in a span of
eight weeks. An ambulatory glucose profile (AGP) of the
patient was taken and is depicted in Figure 1.
As shown in Figure 1, the patient had a daily average glucose
level of 307 mg/dL. In addition, the patient was above the
target blood glucose levels with a 14-day TIR of only 9% (ideal
TIR should be more than 70%). Considering the deranged
glucose parameters and glaring postprandial plasma
glucose (PPG) surges, as derived from continuous glucose
monitoring, and the concomitant anti-TB medications that
the patient was on, it was decided to shift the patient to a
longer acting coformulation insulin, IDegAsp. In February
2020, the patient was started on IDegAsp at a dose of 14
units at lunch. Over four weeks, the dose was up-titrated to 22
units based on the average of three fasting values. Metformin
and pioglitazone were continued as earlier. Her neuropathy
was managed with gabapentin. The patient was followed up
on a monthly basis in the clinic.
Outcomes and follow-up
The patient was then maintained on the stable dose of 22 units,
and during the follow-up visits, the self-measured plasma
glucose profiles were seen to be within the recommended
target ranges. The AGP profile was done to assess the TIR
spent, the results of which are depicted in Figure 2.
As depicted in Figure 2, the daily average glucose level
during the 14-day period was 134 mg/dL. The patient’s
TIR zoomed to 84% with no episode of hypoglycemia. The
comparisons of the TIR, TBR, and TAR glucose range in
the two AGPs (January 2020 Vs March 2020) are shown in
Figure 3. The anti-TB medications were continued as per
the guidelines, and the patient improved symptomatically.
The patient was declared completely cured of XDR-TB
in February 2021, based on the chest X-ray [Figure 4]
and sputum culture reports. Her HbA1c was reported to
be 7.5% in February 2021. The patient was continued on
IDegAsp, pioglitazone, and metformin.
Discussion
This is a case of an Indian patient with DM who seemed
to have a worsened prognosis of TB given the out-of-
range glycemic values and the progression from MDR to
 Hinduja: Remission of tuberculosis following control of glycemic excursions
Figure 1: Ambulatory blood glucose profile of patient on insulin glargine
Figure 2: Ambulatory blood glucose profile of patient on IDegAsp
XDR-TB. The patient was shown to achieve control once
she was shifted to coformulation insulin, IDegAsp. The
causes of treatment failure could be more extensive TB
disease, an altered immune response in people with DM,
or reduced concentrations of anti-TB drugs in patients
with DM.[8]
Two TB-related conditions exist: latent TB infection and
TB disease. Although in this case it cannot be clearly
concluded that increased glucose excursion contributed
to the development of active TB, evidence suggests that
      Journal of Diabetology ¦ Volume 13 ¦ Issue 1 ¦ January-March 2022
patients with untreated latent TB infection and DM
are more likely to develop TB disease than individuals
without DM.
Rifampicin and isoniazid have been documented to
interact with OHAs and hinder glycemic control. Insulin
is more efficacious than OHAs in achieving glycemic
control, though the chances of hypoglycemic episodes
increase with insulin use. Using insulin treatment to
replace or add to OHAs when TB is diagnosed in patients
with DM has been recommended for better glycemic
135  
 Hinduja: Remission of tuberculosis following control of glycemic excursions
control, especially in severe TB.[9,10] We, therefore, initiated
insulin glargine at 10 units, which was eventually titrated
up to 24 units.
Figure 3: Ambulatory glucose profile of patient before and after initiation
of IDegAsp. TIR = time per day within target glucose range, TBR = time
below target glucose range, TAR = time above target glucose range
Figure 4: (A) Chest X-ray of patient at confirmation of extensively
drug-resistant tuberculosis in February 2019. (B) Chest X-ray of patient
in February 2021
136 136  Journal of Diabetology ¦ Volume 13 ¦ Issue 1 ¦ January-March 2022
Further, the patient was noted to have uncontrolled blood
glucose levels on the once daily dose of insulin glargine.
The poor prognosis of the patient might have been due to
a higher PPG level given the high (64.1%; above the target
recommended range) carbohydrate content in the diet of
the Indian population.[11]
Personalized pragmatic glycemic targets are, thus, needed
that account for an array of factors, such as severity and
prognosis of a given patient’s TB disease; risk of adverse
events, such as hypoglycemia; duration of diabetes;
comorbidities; age; the patient’s capabilities and treatment
preferences; and available resources.[12] The patient was, thus,
initiated on IDegAsp, which is an coformulation insulin that
consists of 70% insulin degludec and 30% of insulin aspart.
The patient achieved target glycemic control after switching
to the coformulation insulin. The AGP profile reflected the
efficacy of the molecule regarding both FPG and PPG
control as well as the convenience that was provided, thus
ensuring adherence to the therapy. In a study by Onishi
et al.,[13] IDegAsp has been shown to provide superior long-
term glycemic control compared with insulin glargine, with
similar FPG and doses and numerically lower rates of the
overall and nocturnal hypoglycemia.
Thus, the overall benefit provided by the coformulation
insulin might have been because of the better TIR
(lesser variability) throughout the day, total control
of fasting as well as PPG, longer duration of action of
the basal component, that is, insulin degludec, and the
lesser hypoglycemia. The patient was thereafter noted to
respond to anti-TB medications symptomatically and was
declared clinically cured of TB.
Conclusion
The management of DM in TB should be aggressive and
an optimal blood glucose control results in a better patient
outcome; therefore, vigorous efforts should be made to
achieve such control. Timely initiation of insulin therapy
should offer benefit in controlling the glycemic excursions
that are otherwise not controlled by multiple oral antidiabetic
agents. Although slightly costlier than basal insulin,
coformulation insulin, such as IDegAsp, is a pragmatic
choice considering the safety, efficacy, convenience, lesser
variability, and longer duration of the action that it offers.
Acknowledgment
The author would like to thank APCER Life Sciences,
India for providing editorial assistance and submission-
related support for this article.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 Hinduja: Remission of tuberculosis following control of glycemic excursions
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