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Introduction: Type 2 diabetes mellitus (T2DM) is a growing condition that hinders the treatment and control of tuberculosis (TB). Several factors promote this comorbidity showing variations according to characteristics of the population affected. The objective was to identify the factors associated with the comorbidity of TB-T2DM in a rural population of Oaxaca, Mexico. Methodology: This was an unpaired case-control study. Descriptive statistics was performed for clinical and sociodemographic variables. Logistic regression was used to calculate odds ratio (OR) to identify associated factors with TB-T2DM binomial. Results: 126 controls (TB+ T2DM-) and 69 cases (TB+ T2DM+) were included. 43% were considered as indigenous population. Significant differences were found according to the groups. Treatment failure was higher in individuals with binomial (p = 0.015), as well as a higher bacillary load (two crosses) and presence of pulmonary TB (p ≤ 0.001). Association analysis showed that the risk factors of binomial were: female sex (OR = 2.47; 95% CI 1.24-4.92), age ≥ 45 years (OR = 2.90; 95% CI 1.42-5.92), body mass index ≥ 25 kg/m2 (OR = 2.69; 95% CI 1.25-5.77) and presenting > 6 symptoms (OR = 2.71; 95% CI 1.19-6.14). Conclusions: This is the first report of this comorbidity in a rural Mexican population. The results highlight the growing problem of TB-T2DM, and the need to address the issue from an integral and gender perspective. Furthermore, mandatory screening is necessary in patients with T2DM to improve early diagnosis of TB and T2DM. This would promote better management of both conditions. Inglés