High Prevalence and Heterogeneity of Diabetes in Patients With TB in South India: A Report from the Effects of Diabetes on Tuberculosis Severity (EDOTS) Study

Abstract

Background: Previous studies reported an association of diabetes mellitus (DM) with TB susceptibility. Many studies were retrospective, had weak diagnostic criteria for DM, and did not assess other comorbidities. The Effects of Diabetes on Tuberculosis Severity (EDOTS) study is addressing these limitations with a longitudinal comparison of patients with TB who are classified as diabetic or normoglycemic according to World Health Organization criteria. We report interim findings after enrolling 159 of a planned 300 subjects.

Methods: A cohort study of patients with TB in South India with DM or normoglycemia defined by oral glucose tolerance test (OGTT) and fasting glucose. Glycohemoglobin (HbA1c), serum creatinine, lipids, and 25-hydroxyvitamin D were measured at enrollment. Patients were monitored monthly during TB treatment, and HbA1c measurement was repeated after 3 months.

Results: Of 209 eligible patients, 113 (54.1%) were classified as diabetic, 44 (21.0%) with impaired glucose tolerance, and 52 (24.9%) as normoglycemic. More patients with diabetes were detected by OGTT than by HbA1c. Diabetes was a newly received diagnosis for 37 (32.7%) in the DM group, and their median HbA1c (6.8%) was significantly lower than in those with previously diagnosed DM (HbA1c, 10.4%). Among 129 patients monitored for 3 months, HbA1c declined in all groups, with the greatest difference in patients with a newly received diagnosis of DM.

Conclusions: Early EDOTS study results reveal a strikingly high prevalence of glycemic disorders in South Indian patients with pulmonary TB and unexpected heterogeneity within the patient population with diabetes and TB. This glycemic control heterogeneity has implications for the TB-DM interaction and the interpretation of TB studies relying exclusively on HbA1c to define diabetic status.

Keywords: chest imaging; diabetes; global medicine; tuberculosis.

Figure 1

Summary of patients screened, enrolled, and monitored in the study. See the Materials and Methods section for details of subjects who were excluded or withdrawn. DOTS = directly observed therapy, short course; FPG = fasting plasma glucose; KDM = known diabetic; NDM = new diabetic; NG = normoglycemic; OGTT = oral glucose tolerance test; pre-DM = prediabetic. ^aSix patients withdrew after OGTT (two NDMs and four NG patients). ^bNegative enrollment culture. ^cWithdrawn from study. ^dTwenty-four enrolled patients were unavailable for month-3 analysis as detailed in the Materials and Methods section.

Figure 2

Sputum culture conversion by diabetic status. The curves for KDMs and NDMs virtually overlapped. Trends for differences between groups did not reach statistical significance. See Figure 1 legend for expansion of abbreviations.

Figure 3

Radiographic TB severity score by diabetic status and time point. The top and bottom of each box represent the first and third quartiles, respectively; the line within each box indicates the median, and the ends of the whiskers represent the maximum and minimum range. The differences between scores at enrollment (0) and the completion of TB treatment (month 6) within each group were statistically significant (P ≤ .006). At month 0 there were 73 KDMs, 32 patients newly diagnosed with DM (New DM), and 44 normoglycemic (NG) patients. At month 6 there were 19 KDMs, 13 patients newly diagnosed with DM, and 11 NG patients. The trends for differences between groups did not reach statistical significance. See Figure 1 legend for expansion of abbreviations.

Figure 4

Glycohemoglobin (hemoglobin A1c, or HbA1c) levels in patients with diabetes (DM), stratified by time of DM diagnosis. The proportionate distribution of HbA1c at enrollment (A) and 3 months after enrollment and TB treatment initiation (B) is shown for KDMs and NDMs. See Figure 1 legend for expansion of abbreviations.