Tuberculosis 116 (2019) S59–S65

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Tuberculosis
journal homepage: www.elsevier.com/locate/tube

Diabetic trends and associated mortality in tuberculosis patients in Texas, a T

large population-based analysis
Duc T. Nguyen, Edward A. Graviss∗
Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA

ARTICLE INFO ABSTRACT

Keywords: Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) is a major public health
Tuberculosis challenge worldwide. This analysis aimed to determine the risk factors and trends associated with TB-DM
Diabetes morbidity and mortality.
Risk score Methods: Risk factors for TB-DM morbidity and mortality were identified by logistic regression using de-iden-
Mortality
tified surveillance data of all TB patients from Texas, USA. reported between 01/2010–12/2016. Non-parametric
TB-Diabetes
testing was used for the morbidity and mortality trends.
Trend
Prevalence Results: From 2010 to 2016, 1400/9002 (15.6%) TB patients were diabetic with an annual prevalence increase
from 12.5% to 18.7% (p = 0.005). Reported TB-DM patients had a higher mortality (10.3%) than non-DM
patients (7.6%, p = 0.001) with nearly a 3-fold increase in the odds of death (overall and during treatment).
Older age, being Hispanic, chronic kidney failure, pulmonary cavitation and positive TB culture or smear were
associated with TB-DM. Age ≥45, US-birth, resident of long-term care facility, injecting-drug user, chronic
kidney disease, TB meningitis, abnormal chest radiograph, non-conversion of culture, and HIV(+) were in-
dependently associated with a higher mortality.
Conclusions: TB-DM is an increasing public health problem in Texas with significantly high mortality. Risk
factors for mortality determined by multivariate modeling will provide a foundation for the development of
more effective strategies for TB-DM management.

1. Introduction sputum conversion, and treatment failure or death [6–9].

Tuberculosis (TB) is one of the leading causes of death due to an
infectious diseases with an estimation of 10.4 million new TB cases and
nearly 1.7 million deaths worldwide in 2016 [1]. Although the TB in-
cidence declined by about 1.4% per year between 2000 and 2016, this
decreasing rate is still far below the goal of 4.5% per year by 2020 set
by the World Health Organization (WHO)'s End TB Strategy [1]. Among
the potential challenges that prevent TB programs from achieving the
goal of eliminating TB by the end of this century, the global steady
increase of obesity and diabetes (DM) cases may play a major role with
an estimated frequency of 424.9 million DM patients in 2017 and
projected to be 628.6 million in 2045 [2,3]. Compared with non-DM
patients, diabetic patients may have up to 4-fold increase in the risk of
active TB [4]. Meta-analyses have suggested a high prevalence of DM
among TB patients, which ranges from 1.9% to 45% [5]. Many studies
have also reported significantly higher adverse TB treatment outcomes
in TB-DM patients such as severe clinical manifestations, delayed
In the United States (US), TB-DM comorbidity remains a major
public health problem. In 2016, 16.4% (1524) of TB patients also re-
ported having diabetes, nearly double the DM prevalence of 9.4% in the
US general population [10]. One of the states with the highest TB
prevalence in the US, Texas also has a DM prevalence of 11.2%, which
is higher than the national average [11]. The prevalence of TB-DM
comorbidity is also alarmingly high (up to 39%) in certain Texas sub-
populations [12]. However, information regarding the association be-
tween TB-DM comorbidity and mortality were inconsistently reflected
in literature. For different populations in the US, some analyses re-
ported no significant difference in the mortality or even lower mortality
during treatment in TB-DM patients compared with non-diabetic TB
patients [13,14]. Little in-depth and updated state-wide information is
available regarding the trends of TB-DM and the risk factors associated
with the morbidity and mortality in TB-DM individuals in settings of
low TB prevalence. Additionally, the lack of a standardized prognostic
system to predict the mortality risk during TB treatment remains a

∗
Corresponding author. Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Mail Station: R6-414, 6670 Bertner, Houston, TX
77030, USA.
E-mail address: eagraviss@houstonmethodist.org (E.A. Graviss).

https://doi.org/10.1016/j.tube.2019.04.011
Accepted 9 October 2018
1472-9792/ © 2019 Elsevier Ltd. All rights reserved.
D.T. Nguyen and E.A. Graviss
challenge for health care providers in managing TB-DM patients.
Therefore, the present study aimed to determine the trends and risk
factors associated with the morbidity and mortality in TB-DM patients
using state-wide surveillance data.
2. Methods
De-identified surveillance data from the Centers for Disease Control
(CDC)'s Tuberculosis Genotyping Information Management System
(TBGIMS) of all TB confirmed patients from the state of Texas reported
between 01/2010 through 12/2016 were included in this retrospective
data analysis. According to the CDC's reference guide, TB-DM in the
TBGIMS data set was defined as TB patients who had a documented
diagnosis of diabetes mellitus (type I or type II) either before or at the
time of TB diagnosis. Diabetes diagnosis was obtained from the patient's
medical chart or from a reliable source such as the health care provider.
Undocumented reporting from patient or persons other than health care
providers were not accepted [15].The conversion of specimen TB cul-
tures was defined as a patient who had an initial positive TB culture
that converted to a documented negative TB culture without converting
back to positive TB culture during the entire treatment course [15,16].
Patient characteristics were reported as frequency and proportion.
The difference between diabetic and non-diabetic patients was com-
pared using the Chi-squared or Fisher's exact tests as appropriate.
Spatial distribution of TB-DM cases was presented by Stata's Geographic
Information Systems (GIS) mapping function. A non-parametric trend
test was used for the morbidity and overall mortality trends.
Logistic regression analyses were used to determine prognostic
factors associated with (1) overall mortality (death at diagnosis plus
death during TB treatment) and (2) mortality during TB treatment. All
patients were used in the overall mortality analyses while only reported
patients who either died during treatment or completed the treatment
were used in the analyses regarding mortality during TB treatment.
Variables with a p-value < 0.2 in the univariate analysis or considered
as clinically significant including age and race/ethnicity were further
evaluated in the multiple logistic regression modeling. Variable selec-
tion for the multiple logistic regression was conducted using the
Bayesian model averaging (BMA) method [17]. Model discrimination
was assessed using the area under the receiver operating characteristic
(ROC) curve (AUC). Model calibration was performed using the
Hosmer-Lemeshow goodness-of-fit test. Stratification by TB-DM status
was done to identify if there is any difference in the risk factors af-
fecting the patient mortality. All analyses were performed with Stata
MP15.1 (StataCorp LLC, College Station, TX). A p value < 0.05 was
considered statistically significant.
3. Results
In 9002 confirmed TB patients in Texas who were reported to the
National TB Surveillance System (NTSS)'s TBGIMS database from 01/
2010 to 12/2016, 1400 (15.6%) were also diagnosed as having dia-
betes. In the TB-DM group, 32 (2.3%) patients died at time of diagnosis
and 112 (8.0%) died during TB treatment. In non-DM TB patients, 157
(2.1%) died at time of diagnosis and 418 died during TB treatment
(5.5%). The overall mortality in TB-DM and non-DM TB patients was
10.3% and 7.6%, respectively (Fig. 1).
Among 1400 TB-DM patients, Hispanic patients were dominant
(67.6%, Table 1) over other ethnic groups such as Asian (13.8%), Black
(10.7%), white (7.1%) and Other (0.7%) (data not shown). GIS map-
ping on the distribution of TB-DM cases suggested a higher TB-DM
burden in urban counties and in counties along the Mexican border
(Fig. 2). The ten counties with the highest number of TB-DM patients
were Harris (345/2141, 16.1%), Dallas (153/1290, 11.9%), Hidalgo
(143/509, 28.1%), Bexar (88/565, 15.6%), Tarrant (67/538, 12.5%),
Cameron (65/383, 17.0%), El Paso (52/295, 17.6%), Travis (52/356,
14.6%), Webb (49/241, 20.3%) and Starr (14/53, 26.4%) (data not
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Tuberculosis 116 (2019) S59–S65
Fig. 1. Flowchart of the study population.
shown).
The prevalence of diabetes in TB patients in Texas has consistently
increased from 12.5% in 2010 to 18.7% in 2016 with a positive overall
trend z = 4.50, p < 0.001 (Fig. 3). Compared with non-diabetic TB
patients, TB-DM patients were significantly older with 78% of patients
age ≥45 years (versus 44.3%, p < 0.001), more likely to be Hispanic
ethnicity (adjusted odds ratio [aOR] 2.61, 95% confidence interval (CI)
2.23, 3.05, p < 0.001) and diagnosed with chronic kidney failure (aOR
5.20, 95% CI 3.34, 8.08, p < 0.001). TB-DM patients were more likely
to have pulmonary cavitation (aOR 1.61, 95% CI 1.39, 1.87,
p < 0.001) and a positive TB culture, nucleic acid amplification (NAA)
or acid-fast bacilli (AFB) smear testing (aOR 1.77, 95% CI 1.43, 2.19,
p < 0.001) than non-diabetic TB patients. Non-diabetic TB patients
had a higher proportion of homelessness, being an inmate of a correc-
tional facility, non-injecting drug user or excessive alcohol consumption
compared with TB-DM patients (Table 1).
From 2010 through 2016, non-diabetic TB patients had a significant
decrease in the mortality with an overall negative trend z = −3.33,
p = 0.001. Meanwhile, the mortality was not significantly different
over time in TB-DM patients (z = 0.50, p = 0.62) and this mortality
was always significantly higher than that of non-diabetic TB patients
(z = 3.05, p = 0.002) (Fig. 4). Findings regarding the crude and ad-
justed associations between characteristics and overall mortality are
reported in Table 2. The multiple logistic regression modeling indicated
that TB-DM patients had nearly a 3-fold increase in the odds for overall
death in TB-DM compared with non-diabetic TB patients (aOR 2.75,
95% CI 1.40, 5.39, p = 0.003). Age ≥45 years, being born in the US,
being a resident of a long-term care facility, injecting drug user (IDU),
having chronic kidney failure, abnormalities on chest radiograph con-
sistent with tuberculosis (TB-CXR), TB meningitis, miliary TB, being an
organ transplant recipient, having a non-conversion of specimen TB
cultures, and having a positive or unknown HIV status were in-
dependently associated with a higher overall mortality (Table 2). After
stratification by the diabetic status, age ≥45, being US-born, TB me-
ningitis, TB-CXR and positive or unknown HIV status remained sig-
nificant in the association with a higher overall mortality (Table 3).
The analysis for the mortality during treatment was conducted on
7740/9002 (86%) patients who received TB treatment and had an
outcome as either “died during treatment” (n = 530, 6.9%) or “com-
pleted the treatment” (n = 7210, 93.2%). TB-DM was significantly as-
sociated with the mortality during TB treatment in multivariate analysis
(aOR 2.43; 95% CI 1.13, 5.23; p = 0.02). Age ≥45, being US-born,
resident of long-term care facility, organ transplant recipient, having
chronic kidney failure, TB meningitis, miliary TB, TB-CXR, cultures not
converted from positive to negative, and positive or unknown HIV
status were independently associated with mortality during TB treat-
ment (Table 4).
4. Discussion
Using the population-based surveillance data of the state of Texas
during a 7-year period (2010–2016), our analyses found a significantly
increasing trend of TB-DM comorbidity in this state. This finding is even
D.T. Nguyen and E.A. Graviss Tuberculosis 116 (2019) S59–S65

Table 1
Characteristics associated with diabetes in TB patients in Texas, 2010–2016.
Characteristics Total (N = 9002) Non-diabetes Diabetes Unadjusted OR (95% Adjusted OR (95% Adjusted p-value
(n = 7602) (n = 1400) CI) CI)

Age (years)
0–14 580 (6.4) 578 (7.6) 2 (0.1) 0.21 (0.05, 0.91) 0.47 (0.10, 2.17) 0.33
15–24 1041 (11.6) 1024 (13.5) 17 (1.2) (Reference) (Reference)
25–44 2935 (32.6) 2646 (34.8) 289 (20.6) 6.58 (4.01, 10.79) 11.71 (6.15, 22.27) < 0.001
45–64 2984 (33.1) 2265 (29.8) 719 (51.4) 19.12 (11.75, 31.10) 34.41 (18.21, 65.03) < 0.001
≥65 1462 (16.2) 1089 (14.3) 373 (26.6) 20.63 (12.60, 33.80) 27.02 (14.18, 51.48) < 0.001
Male gender 5872 (65.3) 4966 (65.4) 906 (64.7) 0.97 (0.86, 1.10)
Hispanic 4701 (52.2) 3754 (49.4) 947 (67.6) 2.14 (1.90, 2.42) 2.61 (2.23, 3.05) < 0.001
US-born 3952 (43.9) 3441 (45.3) 511 (36.5) 0.70 (0.62, 0.78) 1.02 (0.87, 1.20) 0.79
Homeless 502 (5.6) 457 (6.0) 45 (3.2) 0.52 (0.38, 0.71) 0.48 (0.32, 0.71) < 0.001
Inmate of a correctional facility 928 (11.5) 885 (12.9) 43 (3.6) 0.25 (0.18, 0.34) 0.30 (0.21, 0.42) < 0.001
Resident of long-term care facility 112 (1.2) 87 (1.1) 25 (1.8) 1.57 (1.00, 2.46)
IDU 221 (2.5) 199 (2.6) 22 (1.6) 0.59 (0.38, 0.93)
Non-IDU 886 (9.8) 808 (10.6) 78 (5.6) 0.50 (0.39, 0.63) 0.64 (0.47, 0.88) 0.01
Excessive alcohol use 1584 (17.6) 1375 (18.1) 209 (14.9) 0.80 (0.68, 0.93) 0.62 (0.51, 0.76) < 0.001
Organ transplant recipient 31 (0.3) 23 (0.3) 8 (0.6) 1.89 (0.85, 4.24)
Chronic kidney failure 131 (1.5) 63 (0.8) 68 (4.9) 6.11 (4.32, 8.65) 5.20 (3.34, 8.08) < 0.001
Immunosuppression (medical condition or 180 (2.0) 141 (1.9) 39 (2.8) 1.52 (1.06, 2.17)
medication)
Pulmonary TB 7727 (85.8) 6464 (85.0) 1263 (90.2) 1.62 (1.35, 1.96)
TB site, cervical lymph 435 (4.8) 413 (5.4) 22 (1.6) 0.28 (0.18, 0.43)
TB meningitis 175 (1.9) 161 (2.1) 14 (1.0) 0.47 (0.27, 0.81)
Miliary TB 238 (2.7) 200 (2.7) 38 (2.7) 1.02 (0.72, 1.46)
TB-CXR 7501 (83.3) 6273 (82.5) 1228 (87.7) 1.66 (1.35, 2.04)
Cavitation on CXR 2462 (32.9) 1894 (30.2) 568 (46.3) 1.99 (1.75, 2.25) 1.61 (1.39, 1.87) < 0.001
AFB smear (+) 3488 (46.7) 2728 (43.8) 760 (61.2) 2.03 (1.79, 2.29)
Mtb culture (+) 5090 (68.5) 4132 (66.7) 958 (77.6) 1.73 (1.50, 1.99)
Culture not converted (from positive to 923 (10.3) 761 (10.0) 162 (11.6) 0.90 (0.75, 1.09)
negative)
Positive culture, NAA, or AFB smear 6938 (77.1) 5722 (75.3) 1216 (86.9) 2.17 (1.84, 2.56) 1.77 (1.43, 2.19) < 0.001
HIV status
Negative 7192 (79.9) 5996 (78.9) 1196 (85.4) (Reference) (Reference)
Positive 570 (6.3) 543 (7.1) 27 (1.9) 0.25 (0.17, 0.37) 0.33 (0.21, 0.51) < 0.001
Unknown 1240 (13.8) 1063 (14.0) 177 (12.6) 0.83 (0.70, 0.99) 0.83 (0.67, 1.04) 0.10
MDR-TB 65 (0.7) 53 (0.7) 12 (0.9) 1.55 (0.60, 3.97) – –
East Asian 1078 (17.4) 934 (18.3) 144 (13.1) 1.01 (0.78, 1.30) – –

AUC = 0.80. Values are in number (%) unless otherwise indicated; AUC, area under the receiver operating characteristic (ROC) curve; CXR, chest radiograph; TB-
CXR, abnormalities on CXR consistent with tuberculosis; IDU, injecting-drug user; MDR-TB, Multi-drug resistant TB; NAA, Nucleic Acid Amplification; AFB, acid-fast
bacilli.

more concerning when the mortality trend in TB-DM patients was
consistently high compared with non-DM TB patients without a sign of
decrease over the past 7 years despite the fact that TB control strategies
have been deployed and well operated by local and state TB control
programs [18]. Our results from the multivariable modeling suggested
that TB-DM patients have a poorer outcome with nearly a 3-fold in-
crease in the odds for both overall mortality and mortality during
treatment compared with non-diabetic TB patients. These findings
confirm the enormous challenge in managing the combination of TB
and DM, and therefore, urgently suggests for more effective strategies in
managing TB, diabetes, and TB-DM patients to reduce the diseases'
burden and improve patient survival. Early identification of TB-DM
patients who are at high risk of mortality and prompt provision of
appropriate medical support are the most important strategies [19].
Multivariate analysis with stratification by TB-DM status suggested
with an exception of IDU, there was no different in the risk factors. Risk
factors associated with a higher mortality identified by multivariable
modeling (such as older age, being US-born, IDU, chronic kidney
failure, TB meningitis, military TB, TB-CXR, non-conversion of culture,
and positive or unknown HIV status) could be used in the development
of a specific prognostic scoring system for TB-DM patients as suggested
by recent mortality risk score modeling for TB and TB/HIV [19,20]. In
the TB-DM population, TB meningitis, chronic kidney failure, and non-
conversion of sputum were the strongest risk factors for mortality.
These findings are consistent with the current literature [21–23].
Although the association with higher mortality of TB-DM patients
have been recognized in high TB burden settings [5,6,24], few studies
have been conducted in the U.S with inconsistent outcomes [13,25]. In
a retrospective cohort study on 139 adult TB patients, Oursler et al.
reported that TB-DM patients had more than 6-fold increase in the risk
for death during treatment (adjusted hazard ratio HR = 6.7; 95% CI
1.6, 29.3; p = 0.01) [25]. Meanwhile, Magee et al. found no significant
association between TB-DM and all-cause mortality in the multivariable
modeling although they observed a higher mortality during treatment
in the univariate analysis for TB-DM patients in a larger study using
data of adult TB patients reported from the state of Georgia from Jan-
uary 2009 to September 2012 [13]. Using a much larger sample size
and including variables that are routinely collected by most TB pro-
grams, we found a significant difference in the mortality (both overall
and during treatment) in TB-DM patients compared with non-DM TB
patients. Having a robust area under the ROC curves, which ranged
from 0.86 (for overall mortality) to 0.89 (for mortality during treat-
ment), our models have enough power to identify additional risk factors
associated with the TB-DM morbidity and mortality, which were not
considered significant in the analyses by Magee et al. such as TB me-
ningitis, organ transplant recipient or non-conversion of the culture
results [13].
Our multivariable modeling also identified subgroups that are more
likely to be associated DM development. Although screening for DM
have been done routinely for all TB patients, more attention should be
extensively targeted in TB patients of older age, Hispanic ethnicity, or
having chronic kidney failure, pulmonary cavitation and positive cul-
ture, smear or NAA.
In our study, Hispanic patients had more than a 2.6 times higher

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D.T. Nguyen and E.A. Graviss
Fig. 2. Spatial distribution of TB-DM cases in Texas, 2010–2016 TB- DM, tuberculosis-diabetes comorbidity.
Fig. 3. Trend of diabetes prevalence in TB confirmed patients in Texas,
2010–2016.
odds of having comorbid diabetes compared with patients of other
ethnic groups. This finding can be explained by the dominance of
Hispanic patients (52.2%) in the overall TB case count. Additionally,
the Hispanic ethnic group accounts for 40% of the general population in
Texas (second after non-Hispanic whites [41.9%] and much higher than
Blacks [11.5%]) [11]. The dominant of Hispanics, especially Mexican
Americans in the prevalence of TB and diabetes has been observed for a
long time with nearly a 3-fold increase in the odds of having TB-DM
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Tuberculosis 116 (2019) S59–S65
Fig. 4. Trend of mortality in TB confirmed patients in Texas, 2010–2016.
(aOR 2.95; 95% CI 2.61, 3.33) compared with non-Hispanic whites
[26]. The National Health Interview Survey data from 200 to 2005
indicated that US-born Hispanic patients had more twice the odds of
TB-DM [27].Our finding is also consistent with the recent report from
the CDC which reported that the prevalence of TB cases in the Hispanic
population was eight time higher than that in non-Hispanic whites [28].
Being born in countries with high TB prevalence, having poor living
conditions and having obesity and diabetes are probably major con-
tributors to this fact [28].
D.T. Nguyen and E.A. Graviss Tuberculosis 116 (2019) S59–S65

Table 2
Characteristics associated with overall mortality in TB patients in Texas, 2010–2016.
Characteristics Alive or Unknown Dead, overall Unadjusted OR Adjusted OR Adjusted

(n = 8291) (n = 712) (95% CI) (95% CI) p-value

Diabetes 1256 (15.2) 144 (20.0) 1.40 (1.16, 1.70) 2.75 (1.40, 5.39) 0.003
Age ≥45 (years) 3830 (46.2) 616 (85.7) 6.95 (5.62, 8.60) 2.92 (1.50, 5.67) 0.002
Male gender 5369 (64.9) 503 (70.0) 1.26 (1.07, 1.49)
White 914 (11.0) 134 (18.6) 1.85 (1.51, 2.26)
US-born 3533 (42.7) 419 (58.3) 1.88 (1.61, 2.19) 1.51 (1.26, 1.82) < 0.001
Homeless 437 (5.3) 65 (9.1) 1.79 (1.36, 2.35)
Inmate in a correctional institution 905 (12.3) 23 (3.5) 0.26 (0.17, 0.39)
Resident of long-term care facility 77 (0.9) 35 (4.9) 5.45 (3.63, 8.19) 2.39 (1.45, 3.93) 0.001
IDU 189 (2.3) 32 (4.5) 1.99 (1.36, 2.92) 1.73 (1.08, 2.78) 0.02
Non-IDU 810 (9.8) 76 (10.6) 1.09 (0.85, 1.40)
Excessive alcohol use 1430 (17.3) 154 (21.4) 1.31 (1.09, 1.58)
Organ transplant recipient 22 (0.3) 9 (1.3) 4.76 (2.18, 10.38) 1.66 (0.59, 4.68) 0.34
Chronic kidney failure 81 (1.0) 50 (7.0) 7.57 (5.27, 10.86) 4.43 (2.84, 6.92) < 0.001
Immunosuppression (medical condition or medication) 140 (1.7) 40 (5.6) 3.43 (2.39, 4.91)
Pulmonary TB 7100 (85.7) 627 (87.2) 1.14 (0.90, 1.43)
TB site, cervical lymph 428 (5.2) 7 (1.0) 0.18 (0.09, 0.38)
TB meningitis 132 (1.6) 43 (6.0) 3.93 (2.76, 5.59) 6.42 (4.11, 10.02) < 0.001
Miliary TB 191 (2.3) 47 (7.0) 3.12 (2.25, 4.34) 3.03 (2.02, 4.54) < 0.001
TB-CXR 6897 (83.3) 604 (84.0) 1.87 (1.38, 2.52) 2.43 (1.72, 3.42) < 0.001
Cavitation on CXR 2290 (33.2) 172 (28.5) 0.80 (0.67, 0.96)
AFB smear (+) 3238 (46.1) 250 (56.3) 1.51 (1.24, 1.83)
Mtb culture (+) 4726 (67.6) 364 (82.5) 2.26 (1.76, 2.91)
Culture not converted (from positive to negative) 713 (8.6) 210 (29.2) 12.54 (9.71, 16.20) 13.55 (10.28, 17.86) < 0.001
Positive culture, NAA, or AFB smear 6269 (75.7) 669 (93.0) 4.30 (3.21, 5.75)
HIV status
Negative 6805 (82.2) 387 (53.8) (Reference) (Reference)
Positive 500 (6.0) 70 (9.7) 2.46 (1.88, 3.23) 2.07 (1.50, 2.87) < 0.001
Unknown 978 (11.8) 262 (36.4) 4.71 (3.97, 5.59) 3.46 (2.82, 4.25) < 0.001
MDR-TB 59 (0.7) 6 (0.8) 1.00 (0.43, 2.33)
East Asian 980 (17.4) 98 (17.3) 0.99 (0.79, 1.25)
Diabetes × age (≥/ < 45) (interaction term) – – 3.12 (1.53, 6.35) 0.002

AUC = 0.86. Values are in number (%) unless otherwise indicated; AUC, area under the receiver operating characteristic (ROC) curve; CXR, chest radiograph; TB-
CXR, abnormalities on CXR consistent with tuberculosis; IDU, injecting-drug user; MDR-TB, Multi-drug resistant TB; NAA, Nucleic Acid Amplification; AFB, acid-fast
bacilli.

On the GIS mapping of TB-DM distribution across Texas counties,
Harris County and Dallas County had the highest frequencies of TB-DM
cases. This finding is not surprising as these two counties are also the
most populous counties in the state and have the highest number of TB
cases [29]. Having a high proportion of the Hispanic population, the
counties along the Mexican border were also among the counties with
the highest frequencies of TB-DM patients as described in a previous
study [12].
Our study has several limitations. First, given the nature of sur-
veillance data from the National Tuberculosis Surveillance System
where there was some lag time so that the data from local health TB
programs could be submitted, validated and then uploaded into the
TBGIMS database, the data used in our analysis might reflect under-
reporting and as the result, our findings might underestimate the actual

Table 3
Adjusted association of characteristics and overall mortality in TB patients in Texas 2010–2016, stratified by diabetes status.
Non-diabetic patients (n = 7261) TB-DM patients (n = 1299)

Adjusted OR Adjusted Adjusted OR Adjusted

(95% CI) p-value (95% CI) p-value

Age ≥45 (years) 8.96 (6.92, 11.60) < 0.001 2.97 (1.49, 5.93) 0.002
US-born 1.49 (1.21, 1.82) < 0.001 1.65 (1.09, 2.51) 0.02
Resident of long-term care facility 2.81 (1.59, 4.96) < 0.001 1.43 (0.52, 3.97) 0.49
IDU 1.52 (0.89, 2.57) 0.12 3.20 (1.02, 10.03) 0.046
Organ transplant recipient 2.00 (0.63, 6.37) 0.24 1.06 (0.10, 11.29) 0.96
Chronic kidney failure 4.06 (2.12, 7.81) < 0.001 4.99 (2.64, 9.44) < 0.001
TB meningitis 6.85 (4.28, 10.98) < 0.001 4.34 (1.12, 16.90) 0.03
Miliary TB 2.92 (1.86, 4.59) < 0.001 3.32 (1.30, 8.44) 0.01
TB-CXR 2.33 (1.60, 3.40) < 0.001 2.74 (1.19, 6.30) 0.02
Culture not converted (from positive to negative) 11.64 (8.56, 15.83) < 0.001 24.21 (12.53, 46.75) < 0.001
HIV status
Negative (Reference) (Reference)
Positive 1.94 (1.37, 2.74) < 0.001 3.24 (1.19, 8.79) 0.02
Unknown 3.35 (2.66, 4.21) < 0.001 4.05 (2.52, 6.51) < 0.001

AUC = 0.86 for non-diabetic patients and AUC = 0.87 for TB-DM patients. AUC, area under the receiver operating characteristic (ROC) curve; CXR: chest radiograph;
TB-CXR, abnormalities on CXR consistent with tuberculosis; IDU, injecting-drug user; MDR-TB, Multi-drug resistant TB; NAA, Nucleic Acid Amplification; Multiple
logistic regression modeling was conducted on patients having complete data for all the variables in the model.

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Table 4
Characteristics associated with mortality during TB treatment in Texas, 2010–2016.
Characteristics Total (N = 7740) Completed treatment Died during Unadjusted OR Adjusted OR Adjusted
treatment

(n = 7210) (n = 530) (95% CI) (95% CI) p-value

Diabetes 1227 (15.9) 1115 (15.5) 112 (21.1) 1.46 (1.18, 1.82) 2.43 (1.13, 5.23) 0.02
Age ≥45 (years) 3801 (49.1) 3345 (46.4) 456 (86.0) 7.12 (5.55, 9.14) 2.46 (1.16, 5.23) 0.02
Male gender 4967 (64.2) 4593 (63.7) 374 (70.6) 1.37 (1.13, 1.66)
White 906 (11.7) 805 (11.2) 101 (19.1) 1.87 (1.49, 2.35)
US-born 3450 (44.6) 3153 (43.7) 297 (56.0) 1.64 (1.37, 1.96) 1.28 (1.04, 1.59) 0.02
Homeless 409 (5.3) 353 (4.9) 56 (10.6) 2.30 (1.71, 3.09)
Inmate in a correctional institution 643 (9.2) 627 (9.7) 16 (3.3) 0.32 (0.19, 0.53)
Resident of long-term care facility 98 (1.3) 68 (0.9) 30 (5.7) 6.30 (4.06, 9.78) 3.62 (2.06, 6.36) < 0.001
IDU 179 (2.3) 158 (2.2) 21 (4.0) 1.84 (1.16, 2.93) 1.64 (0.91, 2.94) 0.10
Non-IDU 736 (9.5) 675 (9.4) 61 (11.5) 1.26 (0.95, 1.66)
Excessive alcohol use 1348 (17.4) 1232 (17.1) 116 (21.9) 1.36 (1.10, 1.69)
Organ transplant recipient 27 (0.3) 18 (0.2) 9 (1.7) 6.90 (3.09, 15.44) 2.17 (0.73, 6.43) 0.16
Chronic kidney failure 109 (1.4) 68 (0.9) 41 (7.7) 8.81 (5.91, 13.11) 5.45 (3.29, 9.04) < 0.001
Immunosuppression (medical condition or 161 (2.1) 132 (1.8) 29 (5.5) 3.10 (2.06, 4.69)
medication)
Pulmonary TB 6657 (86.0) 6182 (85.7) 475 (89.6) 1.44 (1.08, 1.91)
TB site, cervical lymph 391 (5.1) 385 (5.3) 6 (1.1) 0.20 (0.09, 0.46)
TB meningitis 131 (1.7) 105 (1.5) 26 (4.9) 3.49 (2.25, 5.41) 6.22 (3.56, 10.89) < 0.001
Miliary TB 197 (2.6) 158 (2.2) 39 (7.5) 3.56 (2.48, 5.11) 2.82 (1.79, 4.46) < 0.001
TB-CXR 6489 (83.8) 6017 (83.5) 472 (89.1) 2.26 (1.56, 3.27) 2.74 (1.80, 4.16) < 0.001
Cavitation on CXR 2176 (33.6) 2030 (33.8) 146 (30.9) 0.88 (0.72, 1.08)
AFB smear (+) 3082 (47.2) 2855 (46.4) 227 (59.6) 1.70 (1.38, 2.10)
Mtb culture (+) 4416 (68.0) 4108 (67.2) 308 (81.1) 2.09 (1.60, 2.71)
Culture not converted (from positive to negative) 538 (7.0) 328 (4.5) 210 (39.6) 25.74 (19.69, 33.65) 26.66 (19.90, < 0.001
35.71)
Positive culture, NAA, or AFB smear 5930 (76.6) 5435 (75.4) 495 (93.4) 4.62 (3.26, 6.53) 6.17 (4.16, 9.15) < 0.001
HIV status
Negative 6261 (80.9) 5934 (82.3) 327 (61.7)
Positive 478 (6.2) 422 (5.9) 56 (10.6) 2.41 (1.78, 3.25) 2.33 (1.61, 3.36) < 0.001
Unknown 1001 (12.9) 854 (11.8) 147 (27.7) 3.12 (2.54, 3.84) 2.19 (1.68, 2.84) < 0.001
MDR-TB 42 (0.5) 37 (0.5) 5 (0.9) 1.53 (0.60, 3.91)
East Asian 958 (17.9) 877 (17.8) 81 (18.6) 1.06 (0.82, 1.36)
Diabetes × age (≥/ < 45) (interaction term) – – – – 3.12 (1.39, 7.02) 0.01

AUC = 0.89. Values are in number (%) unless otherwise indicated; AUC, area under the receiver operating characteristic (ROC) curve; CXR, chest radiograph; TB-
CXR, abnormalities on CXR consistent with tuberculosis; IDU, injecting-drug user; MDR-TB, Multi-drug resistant TB; NAA, Nucleic Acid Amplification; AFB, acid-fast
bacilli.

burden of TB-DM in Texas. Secondly, as certain historical information
in the surveillance data was obtained from patient interviews, recall
bias cannot be completely ruled out. Thirdly, information regarding the
body mass index, DM treatment, hemoglobin A1c assay (HbA1c) and
lipid profile was not available. Although lacking these DM-specific
variables, our multivariable models still have a good discrimination
power with the C-statistic values ranging between 0.86 (for overall
mortality) and 0.89 (for mortality during treatment), i.e. the models can
predict the mortality risk in most of the cases. Lastly, as Texas is one of
the states having the highest TB prevalence and a more diverse popu-
lation with 40% being Hispanic and one-third being immigrants, find-
ings from our multivariable modeling might need to be validated in
other populations.
Despite these limitations, our study has notable strengths. Using
population-based surveillance data of the entire state of Texas over a
period of 7 years, our study has provided the state-wide concerning
situation of the TB-DM comorbidity and its associated mortality. With
the multivariable models having robust discrimination power and
having large study sample size, we have been able to discriminate the
significantly higher risk of mortality of the TB-DM compared with non-
DM TB patients as well as to identify the independent risk factors as-
sociated with the mortality in this high-risk population.
5. Conclusions
TB-DM remains a major public health problem in Texas with sig-
nificantly higher mortality compared with non-DM TB patients. While
the mortality significantly decreased from 2010 through 2016 in the
population of non-DM TB patients, no improvement was found in the
mortality of TB-DM patients. These findings raise the urgent need for
developing of more effective strategies in managing this high-risk
subgroup of TB patients. Risk factors for mortality determined by
multivariable modeling may lay a foundation for the development of a
prognostic scoring system, which can be used as a practical tool for
health professionals to quickly identify TB-DM patients who have high
risk of mortality and eventually, to develop more effective strategies to
manage TB-DM patients.
Funding
None.
Conflicts of interest
The authors declare no conflicts of interest.
Financial disclosure
Publication of this supplement was supported by The University of
Texas Health Science Center at Houston.
Acknowledgments
This work was presented in part at the Texas Tuberculosis Research

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D.T. Nguyen and E.A. Graviss
Symposium (TTRS) 2018, El Paso, Texas, USA, sponsored by the Texas
Tech University Health Sciences Center El Paso. The authors acknowl-
edge the selfless work of public health officials and staff at the City of
Houston Bureau of Tuberculosis Control, Houston Department of
Health & Human Services, Harris County Public Health, TB Elimination
Program, Texas Department of State Health Services and the US Centers
for Disease Control that made the data available for use in this analysis.
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