Tuberculosis (TB) remains a major global health challenge, with World Health Organization (WHO) estimates reporting approximately 10.6 million new cases and 1.3 million deaths worldwide in 2022 [1]. While antimicrobial therapy has substantially improved cure rates, a considerable proportion of TB survivors experience chronic respiratory sequelae despite microbiological cure. The World Health Organization (WHO) designates these persistent respiratory sequelae as post-tuberculosis lung disease (PTLD), acknowledging their substantial contribution to long-term morbidity and diminished quality of life among TB survivors [2,3]. In high-burden countries such as India, where both TB incidence and survival rates remain high, the absolute number of individuals at risk of PTLD is considerable.

Spirometry, a simple and inexpensive pulmonary function test, plays a central role in characterizing these sequelae. Meta-analyses indicate that over half of TB survivors develop abnormal ventilatory patterns, with pooled reductions of 20-25% in both FEV₁ and FVC [2,4]. These abnormalities include obstructive, restrictive, and mixed defects, which may result from airway remodeling, parenchymal fibrosis, or pleural involvement. Importantly, pulmonary dysfunction often persists even in asymptomatic survivors, indicating that symptom-based follow-up may underestimate the true burden of PTLD [2,4]. Despite this, spirometry remains underutilized in TB programs, particularly in low- and middle-income countries where resource constraints are common.

The burden of post-TB morbidity is further exacerbated by comorbidities such as diabetes mellitus (DM). Diabetes, which affects over 100 million adults in India, has been independently associated with impaired lung function, typically manifesting as reductions in FEV₁ and FVC with a predominantly restrictive pattern [5,6]. Pathophysiological mechanisms include diabetic microangiopathy, systemic inflammation, and an increased susceptibility to pulmonary fibrosis [5]. Moreover, epidemiological data suggest that diabetes increases both the risk of TB and the severity of long-term sequelae [7,8]. Yet, evidence specifically examining whether coexisting DM modifies the spirometric profile of TB survivors remains sparse, despite the high prevalence of this comorbidity in TB-endemic regions such as South Asia.

This is the First study specifically examining diabetes-TB lung function interactions in South Asian population, addressing under-researched area.

Therefore, the present study was conducted to assess the impact of diabetes mellitus on lung function in adults who have been treated for pulmonary tuberculosis. Specifically, we aimed to compare spirometric volumes and ventilatory patterns between diabetic and non-diabetic TB survivors, assess the prevalence and severity of obstructive, restrictive, and mixed ventilatory defects, as well as analyze bronchodilator responsiveness in both groups. By addressing this knowledge gap, our study seeks to contribute to the evidence base on PTLD and inform the integration of spirometry into long-term follow-up strategies for high-risk populations.

This study aimed to explore the impact of diabetes mellitus (DM) on lung function in patients with a history of pulmonary tuberculosis (PTB) who had completed treatment, had no clinical, microbiological or radiological evidence of active disease, but presented with respiratory symptoms. Specifically, we sought to evaluate lung function in patients with DM through spirometry, compare their pulmonary function results with those of non-diabetic controls, classify ventilatory defects by type and severity, and determine which spirometric patterns were more common in patients with DM.

This cross-sectional observational study was conducted in the Pulmonology Outpatient Department (Chest and TB) of a tertiary-care superspecialty postgraduate government medical college in Bengaluru. The study duration was six months, including planning and data collection. During this period, approximately 12,000 patients visited the respiratory medicine outpatient department, of whom 986 had a history of pulmonary tuberculosis. Of these, 752 had active respiratory infections and were excluded. A further 89 patients were unable to perform spirometry according to ERS/ATS guidelines, and 54 declined to participate. The final study group therefore consisted of 91 participants.

Patients were eligible if they were aged 18 years or older, of either sex, presented with respiratory symptoms, and were advised to undergo pulmonary function testing (PFT), irrespective of diabetes status. Only those with a history of pulmonary tuberculosis who had completed treatment and showed no active clinical or radiological features were included. Exclusion criteria were refusal of consent, active respiratory infections, recent surgery or trauma, and pregnancy or lactation. Data were collected through patient interviews, review of medical histories, and measurement of clinical parameters such as HbA1c, fasting blood sugar (FBS), postprandial Blood Sugar (PPBS), and random blood glucose (RBG). Patients with HbA1c ≥ 6.5%, fasting blood sugar (FBS) > 126 mg/dL and postprandial blood sugar (PPBS) > 200 mg/dL or Random Blood Sugar >200 mg/ dl were classified as diabetics. Spirometry was performed using a regularly calibrated Medisoft HypAir PFS Plethysmograph to assess lung volumes and capacities, in accordance with ATS/ERS guidelines.

Before testing, participants were instructed to withhold bronchodilators: short-acting β₂-agonists for at least 4-6 hours and long-acting agents for 36-48 hours. Spirometry was performed with participants seated upright, feet flat on the floor, after detailed instructions regarding mouthpiece placement and breathing technique. Forced expiratory maneuvers were repeated until at least three acceptable results were obtained. A bronchodilator was administered, and the test was repeated after 15 minutes to assess bronchodilator reversibility (BDR). The primary outcome parameters included forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁/FVC ratio, forced expiratory flow between 25-75% of vital capacity (FEF₂₅-₇₅%), and peak expiratory flow (PEF). Lung function was classified according to ATS/ERS, GOLD, and GINA guidelines.

All statistical analyses were performed using Python (pandas, SciPy, StatsModels), SPSS, Microsoft Excel, and Google Sheets. Continuous variables were first tested for normality using the Shapiro-Wilk test. Data that followed a normal distribution were expressed as mean ± standard deviation and compared using independent t-tests, while non-normally distributed variables were summarized as medians and compared using the Mann-Whitney U test. Categorical variables were analyzed using Pearson’s chi-square or Fisher’s exact test, as appropriate. Correlations between HbA1c levels and spirometric indices were examined using Spearman’s rank correlation. A two-tailed p-value of less than 0.05 was considered statistically significant. In total, 91 adults were analyzed-51 with and 40 without diabetes mellitus-all of whom underwent standardized pre- and post-bronchodilator spirometry.

Table 1: Demographic Characteristics of Diabetic and Non-Diabetic Patients, Including Gender, Weight, Height, and BMI

DM-Diabetes Mellitus, Non DM-Non Diabetes Mellitus

Table 2: Age Distribution Among Diabetic and Non-Diabetic Patients With Treated Pulmonary Tuberculosis

Figure 1: Population Pyramid Showing Age-Wise Distribution of Diabetic and Non-Diabetic Patients With Treated Pulmonary Tuberculosis

The baseline characteristics of the study participants were broadly comparable between groups. The mean age was 54 ± 11 years in the diabetic group and 47 ± 12 years in the non-diabetic group. Body mass index (BMI) was higher among participants with diabetes (29 ± 5 kg/m²) than among non-diabetic participants (26 ± 5 kg/m²). Of the 91 participants, 51 had diabetes mellitus (DM) and 40 were non-diabetic controls, all of whom presented with respiratory symptoms and underwent pulmonary function testing. Gender distribution was similar between groups: 64.7% male and 35.3% female in the diabetic group, and 57.5% male and 42.5% female in the non-diabetic group. Most diabetic participants (21/51) were aged 51-60 years, whereas the largest proportion of non-diabetic participants were aged 41-50 years as seen in Table 1,2 and Figure 1. With respect to BMI, most participants with diabetes were in the pre-obese range, whereas non-diabetic participants were predominantly of normal weight.

Figure 2: Alluvial Diagram Depicting the Relationship Between Diabetes Status, Spirometric Abnormalities, and BMI Categories in Treated Pulmonary Tuberculosis Patients

Ventilatory abnormalities were common, with obstructive defects predominating in both groups. Overall, 36 participants with diabetes (70%) and 20 without diabetes (50%) demonstrated obstructive ventilatory patterns. Mixed ventilatory defects were observed in two participants with diabetes (4%), whereas restrictive patterns were identified in four non-diabetic participants (10%) (Figure 2). A sex-based analysis showed that obstructive defects were more frequent among diabetic men (41%) and women (29%) compared with their non-diabetic counterparts (28% and 23%, respectively). Normal ventilatory patterns were observed more often among non-diabetic participants (28%) than among those with diabetes (12%). Age-specific analysis further indicated that obstructive defects were most prevalent among diabetics aged 51-60 years and non-diabetics aged 41-50 years.

Across BMI categories, distinct ventilatory patterns were also evident. Among participants with diabetes, most abnormalities were obstructive, concentrated in the normal, pre-obese, and obesity I ranges; restrictive and mixed patterns were less frequent, and the few underweight cases were exclusively obstructive. In the non-diabetic group, distribution was more balanced: although obstruction predominated in the normal to pre-obese ranges, a considerable proportion exhibited normal ventilatory function, particularly within the normal BMI range. Overall, increasing BMI from normal to pre-obese and obesity I was associated with a higher prevalence of obstruction in both groups, whereas preserved lung function was more common at lower BMI, especially among non-diabetics (Figure 2).

Most participants with DM (36/51) demonstrated obstructive ventilatory defects. In terms of severity, moderate obstruction predominated among participants with diabetes (41%), whereas mild obstruction was more common among non-diabetic participants (20%). Pearson’s chi-square test revealed no statistically significant association between diabetes status and ventilatory defects (p = 0.075).There was no significant association between BMI and ventilatory defects (p = 0.290 for diabetics; p = 0.398 for non-diabetics).

Figure 3: Pre-Bronchodilator Lung Volumes in Diabetic and Non-Diabetic Patients

DM-Diabetes Mellitus and Non DM-Nondiabetes mellitus Patients

Spirometry confirmed that all measured lung volumes were significantly lower in participants with DM than in those without DM. Forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₀.₅, FEV₃, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of vital capacity (FEF₂₅-₇₅)

Were consistently reduced in the diabetic group (p = 0.005-0.020). Post-bronchodilator spirometry revealed similar results. Despite bronchodilation, participants with diabetes continued to exhibit significantly lower lung function across all parameters, indicating persistent, largely irreversible pulmonary impairment (figure 3, 4) (Table 3).

Figure 4: Post-Bronchodilator Lung Volumes in Diabetic and Non-Diabetic Patients

DM-Diabetes Mellitus and Non DM-Nondiabetes mellitus Patients

Table 3: Spirometric Lung Volumes Pre and Post Bronchodilator in Diabetic and Non-Diabetic Patients with Treated Pulmonary Tuberculosis

Bronchodilator responsiveness (BDR) analysis showed significantly higher proportion of participants with diabetes demonstrated BDR compared with non-diabetic participants. Specifically, 54.9% of participants with diabetes met BDR criteria, defined as an increase of ≥12% and ≥200 mL in FEV₁ or FVC, whereas only 15.0% of non-diabetic participants did so (p = 0.04). This suggests that participants with diabetes had a 3.7-fold greater likelihood of exhibiting airway hyperreactivity. However, the mean absolute increase in FEV₁ was similar between groups (+70 mL in diabetics vs. +80 mL in non-diabetics; p = 0.65), indicating that the higher rate of BDR positivity in diabetics reflected their lower baseline lung volumes rather than greater absolute reversibility (Figure 4) (Table 3).

Table 4: Distribution and Severity of Ventilatory Defects Among Diabetic and Non-Diabetic Patients

Among the 91 participants (51 with diabetes and 40 without), the distribution of spirometric patterns differed between groups. Obstructive changes were more common in participants with diabetes (70.6% vs. 50.0%), whereas a normal pattern was more frequent in those without diabetes (27.5% vs. 11.8%). The overall chi-square test across four categories (obstructive, restrictive, mixed, and normal) approached but did not reach statistical significance (χ²(3) = 6.92, p = 0.075). In a focused 2×2 comparison (obstructive vs. non-obstructive), participants with diabetes had higher odds of an obstructive spirometric pattern (OR = 2.40, 95% CI: 1.01–5.70). The chi-square test indicated statistical significance (p = 0.045), while Fisher’s exact test yielded borderline results (p = 0.053). These findings suggest a potential association between diabetes and obstructive ventilatory changes (table 4 and Fig 2).

The present study demonstrated that patients with diabetes mellitus and a history of treated pulmonary tuberculosis exhibited significantly lower spirometric volumes compared with non-diabetic controls. Similar trends have been reported in previous studies. Lange et al. (2015) [9] demonstrated that diabetes is independently associated with reduced spirometric values, while a meta-analysis by Klein et al. (2019) [10], Which includes 15 studies, found pooled reductions of 7-12% in FEV₁ and 5-9% in FVC among individuals with diabetes. The effect sizes in our study were larger, with reductions of approximately 18% in FEV₁ and 15% in FVC, likely reflecting the older age and higher mean HbA1c levels of our cohort. These differences suggest that poor glycemic control and longer disease duration may accelerate pulmonary decline beyond that described in more heterogeneous populations.

Bronchodilator reversibility (BDR) was more frequently observed in diabetic patients, with 55% demonstrating BDR compared with 15% of non-diabetic counterparts. This observation aligns with the findings of Miravitlles et al. (2020)[11], who described a higher prevalence of BDR in individuals with COPD-diabetes overlap, and Tan et al. (2012)[12] from the BOLD study, who found that diabetes increased the odds of BDR even after adjusting for smoking and BMI. However, although diabetics were more often classified as BDR-positive, the absolute gain in FEV₁ after bronchodilation was similar across groups. This paradox was also highlighted in the COPDGene study (Hanania et al., 2011)[13], where lower baseline lung volumes in diabetics led to higher relative reversibility without greater absolute change. Collectively, these findings suggest that the higher prevalence of BDR in diabetes reflects structural or metabolic airway changes rather than classical bronchospasm, supporting the concept of a “diabetic airway phenotype” with overlapping features of asthma and COPD.

When ventilatory defect types were analyzed, obstructive abnormalities were predominant in both groups but were especially frequent among diabetics, 71% of whom displayed obstruction compared with 50% of non-diabetics. This contrasts with several studies, including Kumari et al. (2021) and Davis et al. (2004)[14,15], which reported restrictive or mixed defects as more common in diabetes. However, our findings are in agreement with the COPDGene study and with Patil et al. (2018)[16], who reported significant obstructive impairment in post-tuberculosis cohorts. Such divergence may be explained by differences in age, BMI distribution, and glycemic control across study populations. Notably, severity grading showed that diabetics were more likely to present with moderate obstruction, whereas non-diabetics tended toward mild disease, a trend also documented by Gupte et al. (2019)[17]. These results suggest that diabetes amplifies the pulmonary consequences of tuberculosis, shifting the burden toward more functionally significant obstructive defects.

The influence of prior tuberculosis on lung function is well established in international literature. Allwood et al. (2021)[18], in a meta-analysis of more than 14,000 TB survivors, reported that 59% had persistent spirometric abnormalities-most commonly obstruction or mixed patterns-even after bacteriological cure. Meghji et al. (2020) [19] further emphasized that asymptomatic TB survivors may still harbor significant impairment, underscoring the need for systematic spirometric follow-up. Our findings corroborate this evidence: none of our participants demonstrated normal spirometry, and obstructive abnormalities remained the dominant defect irrespective of diabetes status. Importantly, our study indicates that diabetes compounds this burden, lowering baseline lung function by an additional 15-20% compared with non-diabetic TB survivors and increasing the likelihood of demonstrable airway hyperreactivity.

Although statistical associations between diabetes and ventilatory defect severity were not significant, the odds ratio suggested that diabetics were nearly three times as likely to develop a ventilatory defect as non-diabetics. This is consistent with the systematic review by Saini et al. (2023) [20], which reported relative risks of 1.4-1.7 for COPD and fibrosis in diabetic cohorts. Our stronger HbA1c-spirometry correlations (r = -0.41 for FEV₁) compared with Zhou et al. (2021) (r = -0.32) likely reflect the poorer glycemic control in our study population, whereas studies of well-controlled diabetics tend to show weaker associations [21].

As a result of these results, it has become increasingly clear that diabetes may be a major driver of long-term pulmonary decline among TB survivors. The predominance of obstructive defects, the persistence of reduced lung volumes despite bronchodilation, and the increased prevalence of BDR positivity all suggest that diabetic lung disease represents a distinct phenotype characterized by irreversible structural impairment combined with heightened airway reactivity. This duality may help explain why diabetes worsens the prognosis of post-tuberculosis lung disease and strongly supports the case for routine spirometric screening in diabetic patients, particularly those with a history of tuberculosis.

Diabetes Mellitus was associated with markedly lower spirometric volumes both before and after bronchodilation, indicating combined obstructive and restrictive impairment. While bronchodilator responsiveness was more frequent among diabetic participants, the absolute gains were modest and comparable to those in non-diabetics, suggesting that baseline deficits in diabetics reflect largely irreversible structural damage. Diabetic TB survivors not only exhibited consistently lower lung volumes but also a higher prevalence and greater severity of obstructive ventilatory defects compared with non-diabetic counterparts. Furthermore, the negative correlation between HbA1c and lung function underscores the detrimental impact of poor glycemic control on respiratory outcomes. Collectively, these findings establish diabetes as an independent driver of post-tuberculosis lung disease and emphasize the importance of routine spirometric surveillance and integrated diabetes-TB care to enable early recognition and tailored management of long-term pulmonary sequelae.

Limitations

The Follwing are limitations of the study First, The cross-sectional design of this study limits causal inference regarding the effect of diabetes on post-tuberculosis lung disease, and longitudinal studies are necessary to establish temporality and assess disease progression Second, This study was conducted in a single tertiary-care center in Bengaluru, which may restrict the generalizability of its findings to rural populations and to regions with differing TB-diabetes epidemiological profiles. Third, selection bias cannot be excluded, as only symptomatic TB survivors attending a specialty clinic were included, potentially overestimating the prevalence of pulmonary impairment while underrepresenting asymptomatic individuals. Fourth, the Key confounding variables-including smoking history, occupational and environmental exposures, duration of diabetes, and the presence of microvascular complications-were not comprehensively assessed in this study. Fifth, single HbA1c value may not fully reflect long-term blood sugar control. Lung function assessment was limited to spirometry, without additional tests such as DLCO, impulse oscillometry, six-minute walk test, or HRCT, which could have provided a more detailed understanding of lung changes. The study also did not consider the possible effects of various anti-tuberculosis regimens, steroid use or specific diabetes medicines, which may have influenced lung function outcomes.

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