Diabetes and Tuberculosis Link Quantified

Diabetes status may play a role in the risk for developing tuberculosis, a new study suggested.

In a Korean population-based study, adults with diabetes had a 48% increased risk for developing tuberculosis compared with adults without diabetes (adjusted HR 1.48, 95% CI 1.42-1.53), Dong Wook Shin, MD, DrPH, MBA, of Sungkyunkwan University School of Medicine in Seoul, and colleagues reported in JAMA Network Open.

This associated risk for tuberculosis also appeared to be tied to the duration of diabetes, with the risk increasing the longer the person had diabetes:

• New-onset diabetes: aHR 1.32 (95% CI 1.23-1.42)

• Diabetes duration less than 5 years: aHR 1.45 (95% CI 1.36-1.54)

• Diabetes duration 5 or more years: aHR 1.57 (95% CI 1.48-1.66)

The extent of risk for tuberculosis also seemed to be dependent on blood glucose levels. Individuals with impaired fasting glucose only — blood glucose levels of 100-125 mg/dL but no diabetes diagnosis — did not seem to be at an elevated risk for infection (aHR 0.97, 95% CI 0.93-1.01).

However, those with new-onset diabetes in the highest decile of fasting blood glucose levels (202 mg/dL or higher) had a 79% higher risk for tuberculosis than those with lower glucose levels (fasting plasma glucose of 126-128 mg/dL).

This finding was expected, the researchers said, noting that a previous study looking at this association found about a 2.2-fold increased risk of tuberculosis in patients with diabetes, including those with a fasting plasma glucose level over 130 mg/dL.

“Diabetes appears to be associated with increased risk of lower respiratory tract infection, including TB [tuberculosis], and to have a profound adverse effect on TB treatment outcomes,” Shin’s group explained. “Even though TB is more associated with other immunosuppressive states, such as human immunodeficiency virus infection, because of the greater numbers, diabetes remains an important factor associated with TB incidence at the population level.”

For the cohort study, the researchers drew upon data on 4,423,177 patients ages 20 and older from the Korean National Health Insurance System database. Only patients without a history of tuberculosis were included. Besides a history of tuberculosis, other exclusion criteria included diagnoses of anemia, cancer, and end-stage renal disease.

Diabetes was defined as an ICD-10 code E11-E14 diagnosis, and all patients with diabetes had to have at least one prescription for a hypoglycemic agent and a fasting plasma glucose measure. Normal glucose was defined as a fasting plasma glucose under 100 mg/dL (n=3,030,004), and impaired fasting glucose was 100-125 mg/dL (n=1,017,410). New-onset diabetes was defined as a glucose level over 126 mg/dL or higher without a formal diagnosis of diabetes (n=135,448).

A total of 128,882 individuals had diabetes for less than 5 years, and 11,433 had diabetes for 5 or more years.

The average body mass index in the cohort was 23.9. Not surprisingly, individuals with the longest duration of diabetes tended to be older, have obesity, and possess more comorbidities like chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, stroke, and dyslipidemia.

During a median follow-up of about 8 years, a total of 26,458 cases of tuberculosis (0.6% of the cohort) were identified.

A limitation to the study was that fasting plasma glucose levels were only monitored once at baseline, and that changes in glucose level after treatment was over were not taken into consideration.

“Nevertheless, it is likely that patients whose diabetes status progressed as a result of poor glucose control during the follow-up duration would have a higher risk of TB,” Shin’s group wrote.

They added that the link with tuberculosis was stronger in male patients. “The exact mechanism for this phenomenon is not fully explainable — testosterone could be a reason,” the team said.