Discussion
Even as overall TB case counts declined 18% in the USA during 2010–2017,8 the prevalence of diabetes as a reported comorbidity among adults with TB disease steadily increased from 15% in 2010 to 22% in 2017. An initial interpretation might be that these findings are not surprising—given the high prevalence of diagnosed and undiagnosed diabetes in the USA—but the age-adjusted prevalence of diabetes during the same period is thought to have stabilized at an estimated 9.4% of the adult US population.11
An important limitation of this analysis is potential misclassification (under-reporting) of diabetes as a comorbidity. The 58 574 patients listed in table 1 as ‘diabetes status unknown’ include both adults who had diabetes ruled out and adults who were not evaluated for diabetes. Although this analysis could not discriminate between the two possibilities, that important distinction is part of the NTSS case report form revised in 2020. Diabetes was added to the form in 2009, so one might expect that health departments more systematically ascertained diabetes status toward the end of the 2010–2017 period. In addition, screening for diabetes might have increased after the 2016 recommendation to screen all patients aged ≥45 years at the start of TB treatment.2 Nevertheless, a strength of this first national analysis of diabetes among persons newly diagnosed with TB disease is that it is based on 71 855 patients with TB, including 13 281 reported to have diabetes as a comorbidity.
Despite this potential misclassification (which would be predicted to bias comparisons toward the null), having diabetes as a comorbidity at time of TB diagnosis appears associated with more severe presentations and poorer outcomes in the USA. Patients with TB who were aged ≥45 years and had diabetes had 70% greater odds of having cavitary TB and 50% greater odds of smear-positive TB. We also found 30% greater odds of dying during treatment. These findings are consistent with previous studies from other parts of the world.3–6 12
In our US analysis, patients with diabetes responded more slowly to TB treatment, as evidenced by a median of 5 more days to attain negative M. tuberculosis cultures. TB treatment regimens for persons with diabetes took a median of 37 days longer to complete. But in contrast with the findings of other studies,4 6 having diabetes did not appear to impede TB treatment completion, despite more complicated case management features, including end-stage renal disease, postorgan transplantation, and long-term care settings. In fact, after excluding deaths, TB treatment completion was >93% (table 2). And although a 2011–2014 study in Tbilisi, Georgia, found that patients with diabetes were more likely to have drug-resistant TB,12 our study found that patients with both TB disease and diabetes in the USA during 2010–2017 were not (table 1).
Our findings underscore the recent national recommendation for baseline diabetes screening among all patients with TB aged ≥45 years and all younger patients with risk factors for diabetes (ie, body mass index >25 kg/m2; first-degree relative with diabetes; Hispanic ethnicity; or African–American, Asian, American Indian/Alaska Native, or Hawaiian Native/Pacific Islander race).2 Like other infections, M. tuberculosis infection can worsen blood glucose control and complicate the clinical management of diabetes. Further, Harries et al have appealed for TB screening among persons with diabetes (ie, bidirectional screening).13 Indeed, global concern about the ‘converging epidemics of tuberculosis and diabetes’ has helped draw attention to the synergistic influence each might have on the other.14 15
The progression of untreated latent TB infection (LTBI) causes most of the TB disease in the USA.8 In older persons, diabetes and the ageing process itself synergistically reduce levels of interferon gamma, impairing cell-mediated immunity and helping to activate progression of long-standing LTBI.16 Both TB disease and LTBI in the USA occur primarily among non-US-born persons.8 17 18 Preventing active, infectious forms of TB disease thus requires scaling up of interventions to detect and treat LTBI in this population.19
The International Diabetes Federation projects that 693 million adults will have diabetes by 2024.20 Our analysis revealed that non-US-born patients with TB aged ≥45 years were reported as having a much higher prevalence of diabetes than US-born patients with TB in the same age group (figure 2), suggesting that the increasing diabetes prevalence worldwide could be affecting TB’s epidemiology in the USA. Addressing that challenge will require coordination between the private sector, where case management of diabetes often resides, and the public health sector, which has been charged with the responsibility for controlling and eventually eliminating TB in the USA.