Diabetes mellitus (DM) and tuberculosis (TB) are two major global health challenges, particularly in high-burden countries like China. Their coexistence, known as DM-TB, creates a complex interplay where each disease exacerbates the other, often leading to poorer outcomes. A recent study published in The Journal of Practical Medicine explored the prevalence of Mycobacterium tuberculosis drug resistance, specifically rifampicin resistance, in DM-TB patients, shedding light on critical risk factors and clinical implications.

Study Design and Methodology

Researchers from Guangzhou Medical University and the Guangzhou Chest Hospital conducted a retrospective analysis of 1,948 DM-TB patients treated between 2018 and 2020. After excluding cases with incomplete data, 1,012 patients with positive tuberculous culture and drug susceptibility test (DST) results were included. The study compared resistance rates to first- and second-line anti-TB drugs and used multivariate logistic regression to identify risk factors for rifampicin resistance (RR-TB).

Key Findings: Rifampicin Resistance in DM-TB Patients

1. Overall Resistance Rates:
   • The total rifampicin resistance rate was 13.3%, significantly higher than the World Health Organization’s (WHO) estimated global rates for the general population (3.6% for new cases and 18% for retreatment cases in 2021).
   • Newly treated patients had a rifampicin resistance rate of 6.8%, while retreatment patients showed a striking 45.9% resistance rate—indicating a critical link between treatment history and drug resistance.
   • Multidrug resistance (MDR-TB, defined as resistance to both isoniazid and rifampicin) affected 11.77% of all cases, with retreatment patients (42.9%) far more likely to be MDR compared to new cases (5.5%).
2. Risk Factors for Rifampicin Resistance:
   • Retreatment history was the strongest independent risk factor, with an odds ratio (OR) of 9.517 (95% CI: 4.333–20.904, P < 0.001).
   • Older age emerged as a protective factor (OR = 0.440, 95% CI: 0.252–0.771, P = 0.004), suggesting younger DM-TB patients are more vulnerable to rifampicin resistance.
   • Clinical markers like hemoglobin, albumin, or HbA1c, a measure of blood sugar control did not directly correlate with rifampicin resistance, challenging prior assumptions about glycemic control’s role in drug resistance.
3. Implications for Treatment:
   • Resistance to second-line drugs like levofloxacin and moxifloxacin was notable, highlighting the need for personalized treatment regimens based on local resistance patterns.
   • Drugs such as bedaquiline, linezolid, and clofazimine—used for multidrug-resistant TB—showed no resistance in this cohort, offering hope for effective treatment when initiated early.

Why This Matters: Addressing a Growing Public Health Threat

DM-TB patients face a double burden: diabetes weakens immunity, increasing TB risk and severity, while TB complicates glycemic control. The study’s finding of elevated rifampicin resistance—especially in retreatment cases—underscores the urgency of early drug resistance testing for this high-risk group. Timely DST can guide precision therapy, reduce treatment failure, and curb the spread of drug-resistant TB.

Notably, the study’s focus on Guangdong province, a densely populated area in China, provides regional data lacking in previous research. While limitations include its retrospective design and potential referral bias (most patients were from a tertiary hospital), the results align with global concerns about rising drug resistance in co-morbid populations.

Call to Action for Clinicians and Policymakers

• Prioritize Routine Resistance Testing: Especially for retreatment DM-TB patients and younger individuals, who show higher resistance vulnerability.
• Strengthen Integrated Care: Manage both diabetes and TB concurrently, ensuring optimal glycemic control and adherence to anti-TB regimens to prevent resistance development.
• Invest in Research: Further studies with larger, population-based samples can validate these findings and inform national strategies for tackling DM-TB and drug resistance.

Objective To investigate the drug resistance of Mycobacterium tuberculosis in patients with diabetes mellitus and pulmonary tuberculosis comorbidity (DM-TB). Methods A retrospective case-control study was conducted to collect 1,948 DM-TB patients diagnosed in the inpatient and outpatient departments of Guangzhou Chest Hospital from January 2018 to December 2020. Among them, 1,012 cases with positive Mycobacterium tuberculosis culture and drug susceptibility test results were screened, and 438 cases with complete data were included after excluding incomplete records. Clinical data including age, gender, hemoglobin, albumin, glycated hemoglobin (HbA1c), lesion extent, number of cavities, treatment history, sputum bacterial load, and rifampicin resistance were recorded. Descriptive statistics and chi-square tests were used to compare first- and second-line anti-tuberculosis drug resistance rates among 1,012 DM-TB patients. Patients were divided into a rifampicin-resistant TB (RR-TB) group (86 cases) and a rifampicin-susceptible TB (RS-TB) group (86 cases randomly selected from 352 rifampicin-susceptible patients). T-tests, rank-sum tests, or chi-square tests were used for group comparisons. Multivariate logistic regression analysis was performed with clinical characteristics as independent variables and rifampicin resistance as the dependent variable to identify risk factors for rifampicin resistance in DM-TB patients. Results The overall rifampicin resistance rate in 1,012 DM-TB patients was 13.3%, with initial treatment resistance at 6.8% and retreatment resistance at 45.9% (χ²=127.956, P=0.000). The multidrug resistance rate was 11.77%, with initial treatment multidrug resistance at 5.5% and retreatment at 42.9% (χ²=191.468, P=0.000). Multivariate logistic regression showed that retreatment (OR=9.517, 95%CI: 4.333–20.904, P=0.000) was an independent risk factor for rifampicin resistance, while older age (OR=0.440, 95%CI: 0.252–0.771, P=0.004) was an independent protective factor. Conclusion The prevalence of rifampicin resistance in DM-TB is relatively high, especially in young and retreatment patients. Timely drug resistance testing in DM-TB populations can facilitate early detection and treatment of rifampicin-resistant tuberculosis.

China has approximately 140 million adults with diabetes mellitus (DM), and its prevalence has increased significantly over the past 30 years. Meanwhile, China is one of the 30 high-burden countries for tuberculosis (TB), ranking third globally in new TB cases and multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). In 2021, China reported about 780,000 new TB cases, including 33,000 new MDR/RR-TB cases. Diabetes is confirmed as a risk factor for TB, while TB exacerbates DM. Both diabetes and rifampicin resistance increase TB mortality, but the relationship between diabetes and TB drug resistance remains unclear. Some studies suggest higher resistance rates in diabetic populations, while others find no difference. This study aimed to analyze rifampicin resistance and risk factors in DM-TB patients in Guangdong province, providing local evidence for rational treatment.

Materials and Methods
Study Population: From January 2018 to December 2020, 1,948 DM-TB patients were enrolled from Guangzhou Chest Hospital. Inclusion criteria: TB diagnosis per WS288-2017, type 2 diabetes per 2020 Chinese Diabetes Guidelines, positive sputum culture with drug susceptibility testing (DST), and complete clinical data. Definitions: MDR-TB = resistance to isoniazid and rifampicin; RR-TB = rifampicin resistance; initial treatment = no prior anti-TB therapy or <1 month of irregular treatment; retreatment = ≥1 month of irregular treatment, treatment failure, or relapse. Methods: Clinical data including HbA1c, lesion extent, and treatment history were collected. DST used the WHO standard proportion method. Statistical analyses included chi-square tests, t-tests, and multivariate logistic regression.

Results
Drug Resistance Profile: Among 1,012 patients, rifampicin resistance was 13.3% (initial: 6.8%, retreatment: 45.9%, P<0.001). MDR-TB rate was 11.77% (initial: 5.5%, retreatment: 42.9%, P<0.001). Resistance to second-line drugs like levofloxacin and moxifloxacin was notable, while bedaquiline, linezolid, and clofazimine showed no resistance.
Risk Factor Analysis: RR-TB patients were younger (52.2 vs. 57.0 years, P=0.012) and more likely to have retreatment history (P<0.001). Multivariate regression identified retreatment (OR=9.517) as a risk factor and older age (OR=0.440) as protective. HbA1c, hemoglobin, and albumin showed no correlation with rifampicin resistance.

Discussion
This study highlights elevated rifampicin resistance in DM-TB, especially in retreatment patients, surpassing global and national estimates. The strong association with retreatment history underscores the need for aggressive resistance testing in previously treated patients. Younger age as a vulnerability factor aligns with global trends, possibly due to higher transmission risk and metabolic interactions. While limitations include retrospective design and referral bias, findings emphasize early DST for DM-TB to improve outcomes and curb resistance spread. Integrated management of diabetes and TB, alongside personalized treatment based on local resistance patterns, is crucial for this high-risk population.

Diabetes and tuberculosis co-infection is a complex, growing challenge, made more daunting by rising drug resistance. This study highlights that retreatment history and younger age are critical red flags for rifampicin resistance in DM-TB patients. By prioritizing early diagnostic testing and personalized treatment, healthcare providers can improve outcomes and mitigate the spread of drug-resistant TB in this vulnerable population. As global efforts to end TB accelerate, integrating diabetes care and resistance monitoring will be key to overcoming this dual epidemic.

Diabetes tuberculosis comorbidity DM-TB drug resistance Multidrug-resistant tuberculosis (MDR-TB) in diabetes Retreatment TB patients resistance Rifampicin resistance risk factors