The Sustainable Development Goals and the End TB strategy aim to end the global tuberculosis (TB) epidemic (1). However, the rate of decline in TB incidence is too slow to achieve the global targets. At the same time, the prevalence of diabetes mellitus (DM) has nearly doubled since 1980, with an even faster increase in developing countries (2). DM triples the risk of TB (3) and doubles the risk of TB relapse (4). There is growing evidence showing that DM is an important risk factor for TB and may even affect disease presentation and treatment response (5). For successful TB treatment, the World Health Organization (WHO) recommends that TB patients should undergo DM screening and receive treatment for DM when appropriate (6,7). TB remains a major public health issue in Nepal. The incidence of TB was estimated to be 154 per 100,000 inhabitants in 2016 (8). Despite the nationwide availability of the Directly Observed Treatment Short course (DOTS) program in public health centers, the slow decline in TB incidence is not sufficient to achieve the national targets. The TB case notification rate has remained unchanged for the last 5 years. However, the different older population showed a steady increase in TB prevalence (9). In addition, previous research reported that DM affects approximately 8.1% of urban residents aged 20 years and older in Nepal (10,11). The impact of DM on TB burden may be more conspicuous in Nepal, where both diseases are prevalent. Thus, the present study aimed to assess the association between DM and TB among residents in urban areas in Nepal. This manuscript served as a starting point for the Nepalese government’s interest in DM screening for TB patients.
Received October 19, 2019. Accepted February 12, 2021. J-STAGE Advance Publication March 31, 2021. DOI: 10.7883/yoken.JJID.2019.375 *Corresponding author: Mailing address: Osaka Medical College, 2-7 Daigaku-chou, Takatsuki, Osaka 569-8686, Japan. Tel: +81-80-1489-0121, Fax: +81-72-684-6517, E-mail: HirayamaTa@mbox.pref.osaka.lg.jp
This descriptive cross-sectional study was performed to determine the prevalence of DM and the clinical factors associated with previously treated TB (PTTB) and new TB cases. The data were collected from the urban DOTS centers of the Kathmandu Valley from November 2014 to April 2015. TB patients aged 18–65 years who met the inclusion criteria and agreed to participate were included in the study. Pregnant women and patients with a blood pressure of <80 mmHg were excluded. The diagnosis of PTTB was considered definite in all patients who had previously been treated for TB and with positive bacteriological test results (smear testpositive, culture-positive, and/or gene Xpert-positive results). New TB patients who started taking TB medications were recruited for comparison with PTTB patients. Similarly, new patients beginning treatment were chosen at random in each facility, and 3 new TB patients were selected after every reported PTTB. If a selected patient did not meet the criteria or refused to participate in the study, the next patient with reported TB was selected as a candidate. The DM condition of TB patients was identified using an algorithm based on the WHO recommended diagnostic criteria for DM and intermediate hyperglycemia (Fig. 1).
In this study, patients receiving any DM medications or insulin injections without further blood examination were categorized as having DM. Rapid tests were performed using FreeStyle Freedom Lite (Abbott Diabetes Care Inc., Alameda, CA, USA) under fasting conditions. DM was diagnosed in patients who did not meet the fasting conditions when the results of rapid tests exceeded 200 mg/dl. Oral glucose tolerance tests (OGTTs) were conducted on another day within 8 weeks after the initiation of TB treatment. Patients were diagnosed with DM if the glucose level in the initial blood samples obtained under fasting conditions exceeded 200 mg/dl in the OGTT. The lower values from the rapid tests or the first blood samples were used to determine the fasting blood glucose (FBG) levels. Patients were diagnosed with DM when their FBG level exceeded 126 mg/dl. The second blood samples for the OGTT (OGTT, 2 h) were examined in patients whose FBG level was less than 126 mg/dl. These patients were diagnosed with DM when their OGTT value at 2 h exceeded 200 mg/dl. They were diagnosed with impaired glucose tolerance (IGT) when their OGTT value at 2 h exceeded 140 mg/dl; meanwhile, the patients were diagnosed with impaired fasting glycemia (IFG) when their OGTT value at 2 h was lower than 140 mg/dl and their FBG exceeded 110 mg/dl. All blood samples were transported under cold conditions and tested within 2 h at the Krown Laboratory and Referral Center in Tangal, Kathmandu. This study conformed to the principles outlined by the World Medical Assembly Helsinki Declaration, and ethical approval was obtained from the ethics committee of the National Health Research Council in Nepal and the National Center for Global Health and Medicine in Japan. Consent was obtained from all participants.
The data were collected from 42 urban DOTS centers in Kathmandu (24 centers), Bhaktapur (11), and Lalitpur (7) districts from November 2014 to April 2015. It was difficult to classify PTTB according to the outcome and duration of the recent treatment because only 25 patients (37.3%) could answer the questions related to their previous treatments. The durations of previous treatments were as follows: 3–6 months (2 patients), 6 months (8), 6–9 months (12), and 9–12 months (1). Two patients did not remember their previous treatments. Table 1 shows the results of DM screening in TB patients based on the diagnosis algorithm (Fig. 1). Eight of the 67 PTTB (11.9%) patients and 20 of the 214 new TB patients (9.3%) were diagnosed with DM. Information on patients’ medical history and DM medications obtained from clinical interviews were used to diagnose DM in 4 of the PTTB (50%) patients and 10 of the new TB patients (50%).
Among PTTB patients, one was diagnosed with DM because the result of the rapid test exceeded 200 mg/dl. Two PTTB patients were diagnosed with DM because the results of the rapid test under fasting conditions exceeded 126 mg/dl. Among new TB patients, 3 were diagnosed with DM because the results of the rapid test exceeded 200 mg/dl. Four new TB patients were diagnosed with DM because the results of the rapid test under fasting conditions exceeded 126 mg/dl. the PTTB patients, 62 underwent OGTT. However, only 2 patients had data on the results of their first OGTT, another 2 patients had data on the
results of OGTT at 2 h, and the other patients had data on their glucose test using a rapid test kit but had no data on their OGTT. Five PTTB patients were diagnosed with IGT, and 4 were diagnosed with IFG by OGTT. Among the new TB patients, 201 underwent an OGTT. However, 5 patients had one abnormal value on the test using their initial blood sample, 9 patients did not participate in the examination in which their blood samples were used, 3 were diagnosed with IGT, and one was diagnosed with IFG. Table 2 shows the age distributions of PTTB and new TB patients and the incidence of DM. The mean age of PTTB patients was 41 years, which was older than the mean age (27 years) of the new TB patients. The largest age group of PTTB patients was 18–24 years. Of the 67 PTTB patients, 8 (11.9%) were diagnosed with DM, that is, none from the 18–34-year age group, 3 (20%) from the 35–44-year age group, 1 (7.1%) from the 45– 54-year age group, and 4 (30.7%) from the 55–64-year age group. Among the 214 new TB patients, the 18–24- year age group had the highest number of patients (n = 82). Of them, 20 (9.3%) had DM, that is, none from the 18–24-year age group, 2 (3.7%) from the 25–34-year age group, 4 (11.4%) from the 35–44-year age group, 7 (26.9%) from the 45–54-year age group, and 7 (41.1%) from the 55–64-year age group. A total of 63 patients received the second course of TB treatment, 3 received the third course, and one received more than the third course.
Because of the shift in the age of TB patients, the double burden of DM and TB is becoming a more serious concern for public health programs and individual TB treatment outcomes. The WHO and the International Union against Tuberculosis and Lung Disease (The Union) thus developed the Collaborative Framework for Care and Control of Tuberculosis and Diabetes (6) to assist each country.
The study reported that in the 35–65-year age group, 8 of the 42 PTTB patients and 18 of the 78 new TB patients had DM. In the same age group, 24.2% of PTTB patients and 23.1% of new TB patients had DM as a comorbidity. These rates are higher than the reported DM prevalence in urban areas in Nepal (11,12). The prevalence of DM in Nepal was estimated to be 9% among adults aged 18 years and older in 2014 (13). DM screening should be recommended for both PTTB and new TB patients aged 35 years. DM was screened using clinical interviews, random and fasting blood sugar analyses with rapid kits and blood samples, and the OGTT. The main purpose of DM screening programs is to enable diabetes control at an early stage. This approach improves long-term results by controlling the blood glucose levels (14). To identify patients with early-stage DM, an OGTT is recommended to diagnose IGT and IFG. However, it is difficult to perform an OGTT to diagnose IGT and IFG at DOTS centers in Kathmandu because there is no available apparatus that can be used for blood testing.
To improve TB treatment, the control of DM should be strengthened, and DM management should be Table 1. The number of diagnosed diabetes by screening processes for TB patients PTTB (n = 67) New case (n = 214) Interview about DM medication history 4 10 Rapid test ≥200 mg/dl 1 3 Rapid test ≥126 mg/dl 2 4 First sample of OGTT ≥126 mg/dl 0 1 OGTT 2h ≥200 mg/dl 1 2 DM 8 20 IGT 5 (7.5%) 3 (1.4%) IFG 4 (6.0%) 1 (0.5%) The lower value from the rapid test or the first sample of OGTT was used as data of fasting blood sugar. PTTB, previously treated tuberculosis; IGT, impaired glucose tolerance; IFG; impaired fasting glycaemia. Table 2. Age distribution of previously treatment TB (PTTB) and new TB, and DM in PTTB and in new TB. Age group PTTB DM in PTTB New TB DM in new TB 18–24 15 0 82 0 25–34 10 0 54 2 35–44 15 3 35 4 45–54 14 1 26 7 55–64 13 4 17 7 Total 67 8 214 20 510 enhanced due to the risk of TB relapse. The examination of HbA1c is adequate for managing DM conditions. However, there is no available apparatus that can be used to perform HbA1c examinations as a screening method in a local setting. A clinical interview and rapid glucose tests under random and fasting conditions could be performed to confirm 87.5% of simple postprandial blood glucose measurements with a glucometer 2 h after a meal.
This is the first study to report the prevalence of DM among TB patients in the Kathmandu Valley. DM screening should be performed in TB patients aged 35 years and older. It should be implemented through clinical interviews and glucose testing using rapid kits at DOTS centers. In other developing countries, the DM situation among TB patients living in urban areas might be similar to that in Kathmandu Valley. The development of initial targets and actions to introduce DM screening to TB patients will improve the TB program in developing countries.
This is the first study to report the prevalence of DM among TB patients in the Kathmandu Valley. DM screening should be performed in TB patients aged 35 years and older. It should be implemented through clinical interviews and glucose testing using rapid kits at DOTS centers. In other developing countries, the DM situation among TB patients living in urban areas might be similar to that in Kathmandu Valley. The development of initial targets and actions to introduce DM screening to TB patients will improve the TB program in developing countries.
