Culture conversion and drug susceptibility in drug-resistant pulmonary tuberculosis with type 2 diabetes mellitus on oral regimens

Abstract

BACKGROUND

The simultaneous existence of multidrug-resistant pulmonary tuberculosis (MDR-PTB) and type 2 diabetes mellitus (T2DM) represents a rising threat in high-burden countries such as India. Diabetes has been associated with impaired immune responses and delayed bacteriological clearance, thereby compromising treatment outcomes in patients with multidrug-resistant tuberculosis receiving all-oral longer regimens.

AIM

Impact of T2DM on clinical profile, radiological severity, drug resistance patterns, and sputum culture conversion in MDR-PTB.

METHODS

This prospective observational study included 264 adults with microbiologically confirmed MDR-PTB treated at a tertiary care center in North India over a 12-month period. The participants were classified as diabetic, pre-diabetic, or non-diabetic according to the American Diabetes Association 2023 criteria. Clinical, radiological, microbiological, and drug susceptibility data were analyzed. Time to culture conversion and treatment outcomes were compared across groups using appropriate statistical tests.

RESULTS

Patients with diabetes were older and had higher rates of dyspnea and hemoptysis. Radiologically, they demonstrated significantly higher rates of bilateral lung involvement and lower zone involvement. A higher bacillary load and increased prevalence of inhA and katG mutations were observed among patients with diabetes. Mean time to sputum culture conversion was significantly prolonged in patients with diabetes (132.9 ± 22.3 days) compared with pre-diabetic patients (112.6 ± 7.6 days) and non-diabetic patients (96.9 ± 10.8 days) (P < 0.001).

CONCLUSION

T2DM adversely affects bacteriological response, radiological severity, and treatment outcomes in patients with MDR-PTB on all-oral longer regimens.

Key Words: Multidrug-resistant pulmonary tuberculosis; Type 2 diabetes mellitus; Sputum culture conversion; Drug susceptibility testing; All-oral longer regimen

Core Tip: This study explores how type 2 diabetes mellitus influences the clinical course and treatment response of patients with multidrug-resistant pulmonary tuberculosis receiving an all-oral longer regimen. It demonstrates that patients with diabetes present with more severe disease, a higher bacillary burden, and distinct drug resistance patterns. A key finding is the significantly delayed sputum culture conversion in patients with diabetes compared with the pre-diabetic and non-diabetic groups. This delay is associated with poorer treatment outcomes and higher mortality. Overall, the study highlights the critical need for integrated tuberculosis-diabetes management to improve patient outcomes in high-burden settings.

INTRODUCTION

Multidrug-resistant pulmonary tuberculosis (MDR-PTB) caused by Mycobacterium tuberculosis remains a major cause of morbidity and mortality globally, posing a significant threat particularly in low- and middle-income countries[1]. India bears a disproportionate share of the global MDR-PTB burden (32% in 2025, 25% in 2022, and 27% in 2023 according to the Global Tuberculosis Report)[1-3]. This is further complicated by the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM)[4,5].

Concurrently, T2DM is now recognized as an important modifier of tuberculosis (TB) pathogenesis and treatment response. Hyperglycemia impairs innate and adaptive immune responses, leading to a higher bacillary burden, extensive pulmonary disease, and delayed microbiological clearance[6-8]. These effects lead to continued transmissibility and delayed culture conversion[9-11].

Although the all-oral longer regimen has revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment by improving tolerability and patient adherence, evidence regarding its efficacy in patients with metabolic comorbidities such as T2DM remains limited[12-14]. Sputum culture conversion is an important marker of treatment response and long-term prognosis[15,16]. However, studies examining its trajectory in patients with MDR-TB and diabetes are quite scarce[17,18]. Given the syndemic of diabetes and TB in developing countries, there is an urgent need to better understand this interaction.

Rationale and need for the study

In countries like India, where both diabetes and TB are highly prevalent, the coexistence of MDR-TB and T2DM presents a “double burden”[6,7]. There is currently a lack of empirical data on treatment response in patients with MDR-TB and diabetes, despite the increasing use of all-oral longer regimens. In particular, limited information is available on how T2DM influences the timing of culture conversion, the emergence of new drug resistance, and overall treatment outcomes in patients receiving all-oral regimens[14,17,18]. Studying culture conversion dynamics in this vulnerable population is essential because delayed conversion is a predictor of poor prognosis and the development of extensively drug-resistant tuberculosis (DR-TB)[19-21]. Understanding the pattern and timing of culture conversion, along with changes in drug susceptibility, can help clinicians tailor treatment, identify early warning signs of poor response, and decide whether to intensify or modify therapy[22,23]. The present study, conducted at a tertiary care teaching hospital in North India, is among the pioneering efforts from this region. It aims to evaluate the effect of T2DM on sputum culture conversion, time to culture conversion, and drug susceptibility patterns in patients with MDR-PTB treated with an all-oral longer regimen.

MATERIALS AND METHODS

Study design and setting

This was a prospective observational study conducted over a period of 15 months in 2023-2024 at the Department of Respiratory Medicine in collaboration with the Department of Microbiology at King George’s Medical University (KGMU), Lucknow 226003, Uttar Pradesh. Adult patients (age > 18 years) with microbiologically confirmed MDR-PTB receiving bedaquiline-based all-oral longer regimens were enrolled. Glycemic status was classified according to the American Diabetes Association (ADA) 2023 criteria into pre-diabetic, diabetic, and non-diabetic groups. Standardized protocols were used for sputum microscopy, mycobacterial growth indicator tube (MGIT) liquid culture, line probe assays (LPAs), and drug susceptibility testing.

Sputum samples were collected under standard aseptic precautions and processed in accordance with the Programmatic Management of Drug-Resistant Tuberculosis Guidelines in India (2021)[5]. Mycobacterial culture was performed using the BACTEC MGIT 960 liquid culture system. First-line and second-line LPAs were performed using GenoType MTBDRplus[4,5] and GenoType MTBDRs assays, respectively, for detection of rifampicin, isoniazid, fluoroquinolone, and second-line injectable drug resistance. All microbiological investigations[23] were carried out in the accredited Mycobacteriology Laboratory in the Department of Microbiology at KGMU following standard biosafety and quality control protocols.

Ethical approval

Ethical approval was obtained from the Institutional Ethics Committee of KGMU. Informed consent was obtained from all participants (Letter No. 2967/Ethics/2025).

Study population

Adult patients (age > 18 years) with microbiologically confirmed MDR-PTB receiving a bedaquiline-based all-oral longer regimen were enrolled from both the outpatient and inpatient services of the Department of Respiratory Medicine at KGMU. Glycemic status was classified according to the ADA 2023 criteria. Standardized protocols were used for sputum microscopy, MGIT liquid culture, LPAs, and drug susceptibility testing.

Inclusion criteria: (1) Age > 18 years; (2) Microbiologically confirmed all rifampicin-resistant PTB or MDR-PTB; (3) Classification as pre-diabetic, diabetic, and non-diabetic according to the ADA 2023 criteria; (4) Treatment with all-oral longer MDR-TB regimens (including bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine); and (5) Written informed consent.

Exclusion criteria: (1) Age < 18 years, extrapulmonary TB, human immunodeficiency virus positivity, or immunocompromised status; (2) Chronic kidney or liver disease, pregnancy, or lactation; (3) No treatment with all-oral longer regimens; (4) Pre-extensively or extensively drug-resistant PTB; and (5) T2DM diagnosed by random blood glucose only.

Investigations: (1) Glycemic index: Glycated hemoglobin A1c (HbA1c); (2) TB diagnostics: First-line LPA, second-line LPA, MGIT culture, and drug susceptibility testing; and (3) Glycemic status classification: Controlled (HbA1c < 7%) and uncontrolled (HbA1c ≥ 7%) according to the ADA 2023 criteria.

Sample size: The sample size was calculated based on the India TB Report 2023, which reported a prevalence of MDR/rifampicin-resistant TB of approximately 8.5%[3,4]. Using a precision of 5% and a 95% confidence interval, the sample size was calculated using the formula: n = (Z² × P × (1 − P)) / d². Using Z = 1.96, P = 0.085, and d = 0.05, the required sample size was 122 patients.

Statistical analysis

Data were analyzed using SPSS version 23 (IBM Corp., Armonk, NY, United States). Depending on data normality, appropriate statistical tests (Mann-Whitney U test or Student’s t-test) were used to compare continuous variables. Categorical variables were analyzed using the χ² test. P < 0.05 was considered statistically significant.

RESULTS

Demographics, baseline characteristics, and diabetic status

Compared with the pre-diabetic and non-diabetic groups, patients with TB and diabetes were older, had a lower body mass index (BMI), and exhibited a higher rate of dyspnea. A small proportion of patients with diabetes were on insulin therapy (including some with uncontrolled T2DM), whereas the majority were receiving oral hypoglycemic agents. Most patients belonged to lower socioeconomic strata and were often non-compliant with insulin therapy because of affordability issues and stigma associated with injectable treatment, despite insulin potentially offering better compatibility with anti-tubercular therapy[9]. Patients with diabetes were more likely to experience hemoptysis, dyspnea, and weight loss. These findings suggest that hyperglycemia exacerbates TB severity and negatively impacts general health[10-12] (Table 1).

Table 1 Clinical and demographic characteristics by diabetic status.

Variable	Diabetic (n = 61)	Pre-diabetic (n = 66)	Non-diabetic (n = 137)	P value
Proportion	23.1	25.0	51.9	-
DM control, controlled/uncontrolled	14.8/85.2	-	-	-
Age, year	50.9 ± 13.2	40.7 ± 14.0	27.1 ± 8.1	< 0.001
BMI, kg/m2	17.5 ± 3.8	19.4 ± 3.4	18.9 ± 3.3	0.006
Sex, male	73.8	59.1	52.6	0.020
Smoking, yes	67.2	40.9	21.2	< 0.001
Alcohol, yes	36.1	28.8	13.9	0.001
On OHA	93.4	1.5	0.0	< 0.001
On insulin	4.9	0.0	0.0	0.007
Dyspnea, yes	88.5	53.0	13.9	< 0.001
Weight loss, yes	72.1	97.0	93.4	< 0.001
Hemoptysis, yes	41.0	19.7	31.4	0.033

Data are presented as mean ± SD or %.

BMI: Body mass index; DM: Diabetes mellitus; OHA: Oral hypoglycemic agent.

Association between diabetic status and DR-TB

A significant association was observed between T2DM and DR-TB. Among patients with newly diagnosed MDR-TB, 14.75% had diabetes, 7.58% had pre-diabetes, and 2.19% were non-diabetic (P = 0.004). Most patients with diabetes (83.61%) had a history of treatment for drug-sensitive TB, whereas 8.2% had previously been treated for DR-TB. Among pre-diabetic patients, 90.91% had prior treatment for drug-sensitive TB, with no history of DR-TB treatment. No patients with a history of DR-TB treatment were observed in the pre-diabetic or non-diabetic groups (P < 0.001). These findings highlight the need for integrated TB-diabetes management strategies and increased vigilance in patients previously treated for drug-sensitive TB or DR-TB[24-28] (Tables 2 and 3).

Table 2 Association of diabetic status with newly diagnosed multidrug-resistant pulmonary tuberculosis.

Newly diagnosed MDR-PTB	Diabetic (n = 61)		Pre-diabetic (n = 66)		Non-diabetic (n = 137)		P value
	n	%	n	%	n	%
No	52	85.25	61	92.42	134	97.81
Yes	9	14.75	5	7.58	3	2.19	0.004
Total	61	100.00	66	100.00	137	100.00

MDR-PTB: Multidrug-resistant pulmonary tuberculosis.

Table 3 Association of diabetic status with previously treated drug-sensitive tuberculosis and drug-resistant tuberculosis.

Previously treated	Diabetic (n = 61)		Pre-diabetic (n = 66)		Non-diabetic (n = 137)
	n	%	n	%	n	%
DS-TB	51	83.61	60	90.91	116	84.67
DR-TB	5	8.20	0	0.00	0	0.00

DS-TB: Drug-sensitive tuberculosis; DR-TB: Drug-resistant tuberculosis.

Association of diabetic status with radiological, microbiological, and drug resistance features

Patients with diabetes showed significantly higher frequencies of lower lung zone involvement (70.5%) on radiography, indicating more severe disease (P = 0.028). Bilateral involvement was also more common among patients with diabetes, although it was observed at similar frequencies in the non-diabetic and pre-diabetic groups. However, cavitary disease was observed in 65.7% of non-diabetic patients compared with 63.9% of diabetic patients. Microbiologically, patients with diabetes had a higher bacillary load (80.3% with 3+/2+), although this difference was not statistically significant (P = 0.087). While rpoB mutations were similar across groups, patients with diabetes showed significantly higher inhA (31.1%) and katG (95.1%) mutation rates (P = 0.004 and P = 0.043, respectively). Resistance to pyrazinamide was also more common in patients with diabetes (83.6%), suggesting a trend toward increased drug resistance, although the difference was not statistically significant (P = 0.086) (Table 4).

Table 4 Association of diabetic status with radiological, microbiological, and drug resistance features.

Category	Variable	Diabetic (n = 61)	Pre-diabetic (n = 66)	Non-diabetic (n = 137)	P value
Radiological findings	Cavity	63.9	28.8	65.7	< 0.001
	Nodule	26.2	30.3	32.8	0.646
	Consolidation	42.6	36.4	39.4	< 0.001
	Bilateral involvement	50.8	47.0	50.4	0.024
	Upper zone involvement	63.9	68.2	62.0	0.695
	Middle zone involvement	55.7	45.5	49.6	0.508
	Lower zone involvement	70.5	48.5	53.3	0.028
Sputum smear grade	3+/2+ (high bacillary load)	80.3	60.6	72.2	0.087
	Scanty/negative	6.6/0.0	12.1/3.0	5.1/0.7
LPA resistance	rpoB	98.4	100.0	99.3	0.567
	inhA	31.1	13.6	12.4	0.004
	katG	95.1	84.9	94.2	0.043
Second-line LPA	LFX/MOXI/SLID (resistant)	0.0	0.0	0.0	0.000
DST (Z/MOXI/LZD)	Z resistance	83.6	74.2	68.6	0.086
	MOXI/LZD resistance	0.0	0.0	0.0

DST: Drug susceptibility testing; Z: Pyrazinamide; LFX: Levofloxacin; LPA: Line probe assay; LZD: Linezolid; MOXI: Moxifloxacin; SLID: Sitafloxacin.

Diabetic status vs sputum microscopy and culture

Patients with diabetes consistently showed higher sputum and culture positivity rates from the third to fourth months of treatment compared with the pre-diabetic and non-diabetic patients, with statistically significant differences (P < 0.001). Although all groups achieved conversion by the fifth and sixth months, patients with diabetes, particularly during the initial months of therapy, exhibited delayed sputum and culture conversion[10-12]. Tables 5 and 6 show the detailed distribution of sputum culture conversion results, including positive, negative, report not available, and lost to follow-up categories. These results are summarized in Table 7.

Table 5 Association of diabetic status with sputum culture results from third month to sixth month.

Month	Finding	Status						P value
		Diabetic (n = 61)		Pre-diabetic (n = 66)		Non-diabetic (n = 137)
		n	%	n	%	n	%
Third	Positive	10	16.4	1	1.5	2	1.5	< 0.001
	Negative	46	75.4	44	66.7	107	78.1
	Contaminated	4	6.6	4	6.1	11	8.0
	NA	0	0.0	17	25.8	16	11.7
	LFU	1	1.6	0	0.0	1	0.7
	Death	0	0.0	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Fourth	Positive	6	9.8	0	0.0	0	0.0	< 0.001
	Negative	40	65.6	33	50.0	114	83.2
	Contaminated	7	11.5	5	7.6	13	9.5
	NA	5	8.2	28	42.4	7	5.1
	LFU	3	4.9	0	0.0	3	2.2
	Death	0	0.0	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Fifth	Positive	0	0.0	0	0.0	0	0.0	0.055
	Negative	45	73.8	53	80.3	115	83.9
	Contaminated	0	0.0	0	0.0	2	1.5
	NA	9	14.8	7	10.6	6	4.4
	LFU	5	8.2	6	9.1	14	10.2
	Death	2	3.3	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Sixth	Positive	0	0.0	0	0.0	0	0.0	0.001
	Negative	34	55.7	51	77.3	104	75.9
	Contaminated	1	1.6	0	0.0	3	2.2
	NA	10	16.4	5	7.6	12	8.8
	LFU	9	14.8	11	16.7	18	13.1
	Death	7	11.5	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0

LFU: Lost to follow-up; NA: Not available.

Table 6 Association of diabetic status with sputum microscopy results from third month to sixth month.

Month	Finding	Status						P value
		Diabetic (n = 61)		Pre-diabetic (n = 66)		Non-diabetic (n = 137)
		n	%	n	%	n	%
Third	Positive	8	13.1	1	1.5	1	0.7	0.002
	Negative	52	85.2	64	97.0	134	97.8
	NA	0	0.0	1	1.5	1	0.7
	LFU	1	1.6	0	0.0	1	0.7
	Death	0	0.0	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Fourth	Positive	3	4.9	0	0.0	0	0.0	0.0012
	Negative	51	83.6	65	98.5	129	94.2
	NA	4	6.6	1	1.5	5	3.6
	LFU	3	4.9	0	0.0	3	2.2
	Death	0	0.0	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Fifth	Positive	0	0.0	0	0.0	0	0.0	< 0.001
	Negative	43	70.5	59	89.4	120	87.6
	NA	11	18.0	1	1.5	3	2.2
	LFU	5	8.2	6	9.1	14	10.2
	Death	2	3.3	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0
Sixth	Positive	0	0.0	0	0.0	0	0.0	< 0.001
	Negative	38	62.3	55	83.3	111	81.0
	NA	7	11.5	0	0.0	8	5.8
	LFU	9	14.8	11	16.7	18	13.1
	Death	7	11.5	0	0.0	0	0.0
	Total	61	100.0	66	100.0	137	100.0

LFU: Lost to follow-up; NA: Not available.

Table 7 Association of diabetic status with sputum microscopy and culture results from third month to sixth month.

Month	Category	Diabetic, positive	Diabetic, negative	Pre-diabetic, positive	Pre-diabetic, negative	Non-diabetic, positive	Non-diabetic, negative	P value
Third	Microscopy	13.1	85.2	1.5	97.0	0.7	97.8	0.002
Third	Culture	16.4	75.4	1.5	66.7	1.5	78.1	< 0.001
Fourth	Microscopy	4.9	83.6	0.0	98.5	0.0	94.2	0.0012
Fourth	Culture	9.8	65.6	0.0	50.0	0.0	83.2	< 0.001
Fifth	Microscopy	0.0	70.5	0.0	89.4	0.0	87.6	< 0.001
Fifth	Culture	0.0	73.8	0.0	80.3	0.0	83.9	0.055
Sixth	Microscopy	0.0	62.3	0.0	83.3	0.0	81.0	< 0.001
Sixth	Culture	0.0	55.7	0.0	77.3	0.0	75.9	0.001

Association of diabetic status with outcomes and time to culture conversion

A significant association was observed between diabetic status and treatment outcomes (P < 0.001). Among patients with diabetes, 70.5% survived, 14.8% died, and 14.8% were lost to follow-up. By contrast, no deaths were reported in the pre-diabetic or non-diabetic groups. Survival rates were 83.3% and 86.9%, respectively, with lost-to-follow-up rates of 16.7% and 13.1%. Time to culture conversion was longest in patients with diabetes (mean ± SD: 132.97 ± 22.28 days), followed by pre-diabetic patients (112.58 ± 7.55 days), and non-diabetic patients (96.90 ± 10.82 days), with statistically significant differences across groups (P < 0.001). Post hoc analysis confirmed significant differences among all groups (P < 0.001) (Table 8).

Table 8 Association of diabetic status with outcome and time to culture conversion.

Parameter	Diabetic (n = 61)	Pre-diabetic (n = 66)	Non-diabetic (n = 137)	P value
Outcome				< 0.001
Alive	43 (70.5)	55 (83.3)	119 (86.9)
Dead	9 (14.8)	0 (0.0)	0 (0.0)
Lost to follow-up	9 (14.8)	11 (16.7)	18 (13.1)
Total participants	61 (100.0)	66 (100.0)	137 (100.0)
Time to culture conversion, days
mean ± SD	132.97 ± 22.28	112.58 ± 7.55	96.90 ± 10.82	< 0.001

Data are presented as n (%) unless otherwise indicated.

SD: Standard deviation.

DISCUSSION

This prospective observational study explored how T2DM influences the clinical profile, bacteriological response, radiological severity, and treatment outcomes of patients with MDR-PTB treated with bedaquiline-based all-oral longer regimens. The findings suggest that diabetes influences the clinical course of MDR-PTB, with significant implications for disease burden, microbiological response, and treatment outcomes[20-22].

Patients with T2DM had a significantly lower BMI than those without dysglycemia[6,7], indicating the close epidemiological association between TB and metabolic disease. Clinically, symptoms such as dyspnea, hemoptysis, and weight loss were more common in patients with T2DM, indicating a higher symptom burden and more advanced disease at presentation compared with non-diabetic patients[20,22]. These observations support the concept that TB in individuals with T2DM often manifests at a later stage and progresses more aggressively[20].

An interesting finding was the substantial proportion of inadequately controlled diabetes, with most diabetic patients showing HbA1c levels of ≥ 7%. Chronic hyperglycemia impairs macrophage function, cytokine signaling, and cell-mediated immunity, which together reduce the host’s ability to contain mycobacterial infection[6,7]. However, future prospective multicenter studies with larger sample sizes should specifically evaluate the impact of glycemic control (controlled T2DM vs uncontrolled T2DM) on sputum culture conversion, treatment outcomes, and mortality in patients with MDR-PTB receiving all-oral longer regimens. However, our study was unable to deeply explore these subgroup differences. Moreover, the requirement for insulin therapy in a subset of patients further reflects the metabolic severity in this group and highlights the importance of active glycemic management during prolonged MDR-TB treatment[10-12].

Drug resistance patterns also varied according to glycemic status. Higher frequencies of inhA and katG mutations were observed in patients with diabetes, suggesting a possible association with increased isoniazid resistance in this subgroup, although causal inference cannot be established from the present study design. Low BMI, increasing age, smoking, and bilateral chest involvement may act as confounding factors for antimicrobial resistance. However, rpoB mutations were similarly distributed across all groups.

The exclusive presence of previously treated DR-TB cases among diabetic individuals emphasizes diabetes as a potential risk factor for disease recurrence and resistance amplification. Possible mechanisms involved in this include altered drug pharmacokinetics, reduced drug absorption, and impaired immune-mediated microbiological clearance in the setting of chronic hyperglycemia[12]. These findings collectively suggest the need for resistance monitoring and individualized treatment planning in patients with MDR-TB and diabetes[20-22].

Radiological findings further highlighted the impact of diabetes on disease severity. Patients with diabetes more commonly showed bilateral involvement and lower zone disease, indicating extensive pulmonary pathology. Although not all associations reached statistical significance, the overall pattern suggests prolonged infectivity and delayed response to therapy. Radiological severity may therefore serve as a useful indicator of treatment response, particularly in patients with MDR-TB and diabetes.

Time to culture conversion[10,11,17], a key marker of treatment efficacy and infectivity, was significantly longer in patients with diabetes than in the pre-diabetic and non-diabetic groups. This delay has important clinical and public health implications, including extended periods of infectiousness, increased treatment fatigue, and a potential risk of further resistance development. These findings support the need for intensified microbiological surveillance and, in some cases, prolonged treatment duration in patients with MDR-TB[18,19] and diabetes.

Treatment outcomes followed a clear gradient based on glycemic status. Mortality and loss to follow-up were observed only among patients with diabetes, whereas the pre-diabetic and non-diabetic groups demonstrated better survival. Increased mortality was observed in patients with diabetes. This may be linked to cumulative metabolic stress, hyperglycemia-associated complications, and delayed bacteriological clearance. Higher loss-to-follow-up rates may be related to treatment complexity[20], adverse drug effects, or social and economic barriers, thereby underscoring the need for comprehensive patient counseling, psychosocial assistance, and diabetes education as essential components of MDR-TB management[27,28].

Notably, the pre-diabetic group consistently showed outcomes intermediate between the diabetic and non-diabetic groups. Although mortality was absent in this group, culture conversion was delayed compared with that in the non-diabetic group. This suggests that even early dysglycemia adversely impacts TB treatment response. This relationship highlights the clinical relevance of pre-diabetes and supports early detection and metabolic intervention within TB control strategies.

This research possesses several important strengths that contribute to its scientific validity and applicability to public health practice, as it addresses MDR-TB and T2DM, two major global health challenges with high prevalence in India. All patients were diagnosed using accredited molecular methods (cartridge-based nucleic acid amplification test, LPAs, and MGIT liquid culture). The results are of major utility to national TB elimination programs, especially for developing evidence-based approaches for integrated screening and management of diabetes in patients with MDR-TB.

Limitations

The study has certain limitations as well. Because it was conducted at a single tertiary care center, the findings may not be fully generalizable. The sample size of 264 patients with MDR-TB, enrolled at a single center, may not reflect all potential variability in resistance patterns and glycemic effects within a heterogeneous national population. The study primarily captured resistance at baseline; the emergence of sequential resistance during therapy, which could be influenced by glycemic status, was not investigated.

The sample size was calculated using the prevalence of MDR-PTB in India instead of being based on differences in culture conversion between the diabetic and non-diabetic groups, which may limit statistical precision. Furthermore, the study included a follow-up period of 1 year (patients were recruited from September 2023 to March 2024 and were then followed until December 2024), whereas the all-oral longer MDR-TB regimen recommended under the Guidelines for Programmatic Management of Drug-Resistant Tuberculosis in India (2021) extends up to 18 months. As a result, complete end-of-treatment outcomes could not be uniformly assessed for all participants within the study duration. Therefore, interim outcome measures such as alive, dead, and lost to follow-up were reported to reflect the available follow-up data during the study period.

Potential synergistic side effects resulting from the concomitant use of oral hypoglycemic agents and anti-tubercular therapy could not be assessed. A major limitation was the erratic and delayed reporting of the MGIT liquid culture results, which made it difficult to obtain timely culture conversion data and may have introduced reporting errors, thereby affecting the accuracy and completeness of outcome measures.

Despite these limitations, the findings strongly support integrating diabetes screening and management into MDR-TB treatment strategies. Addressing these limitations in future multicenter longitudinal studies with larger cohorts and integrated molecular, pharmacokinetic, and real-time laboratory reporting systems will improve the evidence-based treatment recommendations for MDR-TB and T2DM comorbidity.

CONCLUSION

This study demonstrates a clear association between glycemic status and treatment outcomes in patients with MDR-PTB receiving an all-oral longer regimen. Patients with diabetes experienced delayed sputum culture conversion, higher mortality, and increased loss to follow-up compared with the pre-diabetic and non-diabetic groups, suggesting that diabetes substantially compromises treatment outcome and survival.

The pre-diabetic group showed intermediate outcomes, suggesting that even early disturbances in glucose metabolism can adversely affect TB treatment. These findings highlight the importance of routine screening for diabetes and pre-diabetes in patients with MDR-TB, as well as the need for integrated care models that combine TB treatment with effective glycemic control, close monitoring, and patient-centered support. Such an approach is essential to improve outcomes and reduce mortality in this high-risk population.