Transient Impact of Dysglycemia on Sputum Conversion Clinical Medicine Insights: Circulatory,Respiratory and Pulmonary Medicine among Smear-Positive Tuberculosis Patients in a Tertiary Volume 15: 1–8© The Author(s) 2021 Care Facility in Ghana Article reuse guidelines:sagepub.com/journals-permissions DOI: 10.1177/11795484211039830 Ernest Yorke1 , Vincent Boima1, Ida Dzifa Dey1, Maame- Boatemaa Amissah-Arthur1, Vincent Ganu2, Ernest Amaning- Kwarteng2, John Tetteh1,2 and C. Charles Mate-Kole1,2 1University of Ghana, Accra, Greater Accra, Ghana. 2Korle-Bu Teaching Hospital, Accra, Greater Accra, Ghana. ABSTRACT BACKGROUND: Apart from increasing the risk of tuberculosis (TB), diabetes may be associated with more severe disease and lower rates of sputum conversion among TB patients. METHODS: We conducted a baseline cross-sectional study with a longitudinal follow-up of newly diagnosed smear-positive TB patients for 6 months. Sputum conversion rates between those with dysglycemia and those without were compared at 2 months (end of the intensive phase) and 6 months (end of the treatment). Descriptive statistics and logistic regression were computed to assess factors associated with dys- glycemia as well as sputum conversion. RESULTS: A significantly higher proportion of normoglycemic patients had negative sputum compared with those with dysglycemia (83% vs 67%, P-value< .05) at 2 months but not at 6 months (87% vs 77%, P-value> .05). After controlling for age group and adjusting for other covariates, patients with dysglycemia were 66% less likely to convert sputum than those with normoglycemia. Females were at least 7 times more likely than males and those with high waist-to-hip ratio (WHR) of 88% were less likely compared with those with low WHR for sputum conversion at 2 months, respectively. At 6 months, females (compared with males) and those with high WHR (compared with those with normal WHR) were at over 9 times increased odds and 89% less likely for sputum conversion, respectively. CONCLUSION: A significantly lower proportion of smear-positive TB patients with dysglycemia converted to smear negative after 2 months of treatment but not at the end of the treatment, thus suggesting a transient impact of dysglycemia on sputum conversion. KEYWORDS: Tuberculosis, smear Positive, dysglycemia, sputum Conversion, transient. RECEIVED: April 21, 2021. ACCEPTED: July 26, 2021 DECLARATION OF CONFLICTING INTERESTS: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. TYPE: Original Research Article CORRESPONDING AUTHOR: Ernest Yorke, Department of Medicine and Therapeutics, FUNDING: The authors disclosed receipt of the following financial support for the research, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. Box authorship, and/or publication of this article: This work was supported by the University of GP 4236, Legon, Accra, Ghana. Email: pavlovium@yahoo.com Ghana Office of Research, Innovation and Development (ORID) grant (Grant no. URF/9/ ILG-076/2015-2016). 1. Introduction phase) and 6 months (end of the treatment)9,12 while others Worldwide, tuberculosis (TB) infections are still high despite have shown no relationship between diabetes and sputum the many strategies to curtail it. In 2016, there were an esti- conversion rate at the end of the secondmonth.14,17 More mated 10.4 million new TB cases worldwide with about 1.7 data are needed to help ascertain the impact of dysglycemia million people dying from it, making it the topmost infectious on the sputum conversion rate among TB patients. The add- killer.1 With the high global burden of diabetes and an itional information would help determine if adjustments must increasing trend, especially in type 2 diabetes, the recognized be made to the current treatment regime. Thus, the present reciprocal negative impact of TB and diabetes on each other is study ascertained the impact of dysglycemia on sputum con- likely to worsen.2–4 Diabetes represents a significant popula- version among smear-positive TB patients in a tertiary care tion risk for TB infections of ∼1.5 to 7.8 times5–8 and may setting. also be related to the development of multidrug resistant TB with an odds ratio (OR) of 2.1.9 Diabetes may be asso- ciated with more severe disease, higher rates of reactivation 2. Materials and Methods of old TB foci, more cavitations, and higher risk of death 2.1 Study Design and Site among TB patients.6,9–11 The relationship between rates of The study adopted a cross-sectional baseline assessment with a sputum conversion among TB patients with diabetes or dys- longitudinal follow-up for 6 months at the outpatient referral glycemia appears inconsistent.9,12–16 Some studies have sug- chest clinic of the Korle-Bu Teaching Hospital, which is a ter- gested a reduced rate at 2 months (end of the intensive tiary care facility in Ghana. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 2.2 Participants and Sampling 6.1 mmol/L and 7.8 mmol/L respectively are normal. Diagnoses of impaired or borderline fasting and glucose toler- We consecutively enrolled patients who were either first diag- ance were made when FPG and 2HPP values were 6.1 to nosed at or referred to the Korle-Bu chest clinic as newly diag- 6.9 mmol/L and 7.8 to 11 mmol/L, respectively.24 None of nosed smear-positive TB patients. Included patients were those the participants was known to have diabetes prior to enroll- aged 18 years or older, had no previous TB treatment, and who ment. Patients found to have diabetes were referred to receive gave informed written consent. Patients who were diagnosed appropriate care. with smear-negative TB or extrapulmonary TB, those who The presence of Mycobacterium tuberculosis (MTB) was had previously been treated for TB, or refused to give informed tested using the Cepheid GeneXpert system, a rapid, consent were excluded from the study. nucleic acid amplification test (NAAT) through polymerase Differences in sputum culture conversion rates comparing chain reaction to confirm the diagnosis. Sputum smear pulmonary TB patients with and without diabetes mellitus microscopy using Ziehl–Neelsen staining was however used (DM) from previous studies have varied between zero and 18–22 to ascertain sputum conversion at 2 months (end of the inten-15%. Assuming a 15% difference in sputum conversion sive phase) and 6 months (end of the treatment). The sputum rates between pulmonary TB patients with or without DM, conversion rate was determined as the percent of enrolled 134 smear-positive TB patients would be adequate to detect smear-positive pulmonary TB cases that converted to smear- a difference in sputum conversion based on a power of 80% negative status at 2 months and 6 months. For the purposes and a 2-sided confidence interval (CI) of 90%. Sampling of analyses, participants with “very low” and “low” detected was done on weekdays for 16 months until a sample size of MTB and those with “medium” and “high” detected MTB 200 was obtained of which 171 had complete data. by GeneXpert were recategorized as low and high loads, Anti-TB treatment regimen used included a combination of respectively. rifampicin (R), isoniazid (H), pyrazinamide (Z) and etham- Body mass index (BMI) was calculated and categorized as butol (E) for the intensive phase (first 2 months) while obese, overweight, normal, and underweight based on the only rifampicin (R) and isoniazid (H) were used in the con- cut-offs of 30.0 or more, 25 to 29.9, 18.5 to 24.9, and <18.5 tinuation phase (next 4 months). None of the recruited par- (kg/m2), respectively.25 ticipants admitted to being a known diabetic prior to the study. The center employs the directly observed therapy strategy 2.4 Statistical Analysis (DOTS) to improve compliance to treatment. Moreover, the Data were analyzed with the statistical software Stata version 15 TB control program employs treatment supporters to help after initial capture with Microsoft Excel 2010. Analyses for the patients adhere to their treatment in the community. They various characteristics were performed for patients with com- pay visits and assess compliance to treatment; challenges iden- plete data. For the purposes of analyses, patients were categor- tified are remedied. This ensures a high rate of compliance to ized as either dysglycemia or abnormal (impaired glucose medications and successful treatment outcomes. tolerance and diabetes) or normal using 2HPP values. Sociodemographic, anthropometric, and clinical variables 2.3 Measurements were summarized and compared between these two groups Patients enrolled were given a data abstraction tool to capture using the χ2 test. A similar analysis using FPG was not per- data concerning their sociodemographic and anthropometric formed due to the very few numbers involved. characteristics as well as medical history. Two approaches of statistical analysis were performed To assess their glycemia status, a 75 g oral glucose tolerance involving the descriptive χ2 test and logistic regression analysis. test (OGTT) was administered to all patients. A 10 mL fasting Descriptive cross-tabulation analysis was performed to assess blood sample was taken into fluoridated blood sample tubes covariates significantly associated with 2HPP using the χ2 (kept on ice and centrifuged within 15 min of blood draw), test. Due to the dummy nature of our study outcomes, a ethylene-diamine-tetra-acetic acid (EDTA) tubes, and plain binary logistic regression model was used to test the effect of tubes.23 Patients then received 75 g of glucose in 250 mL of sociodemographic, clinical, and lifestyle factors on 2HPP and water, and after–2-h blood sample was taken into fluoridated sputum conversion separately. Logistic regression analysis was sample tubes and processed similarly as the fasting sample. conducted to estimate factors significantly influencing 2HPP. Plasma glucose was determined using glucose oxidase commer- Age group as the only significant factor influencing 2HPP cial reagent kits and controls (Diasys GmBH, Germany). was controlled and other covariates were adjusted in further Diabetes was diagnosed when the fasting plasma glucose analysis to quantify the impact of 2HPP on sputum conversion (FPG) and the 2-h postprandial (2HPP) blood glucose level for 2 months and 6 months separately by adopting logistic were >7 mmol/L and >11.1 mmol/L, respectively, or on regression. The statistical tests were set at the 5% significance regular medication for diabetes. FPG and 2HPP values below level. Yorke et al. 3 3. Results Table 1. Sociodemographic, lifestyle, and clinical characteristics 3.1 Participant Characteristics associated with 2HPP among TB patients The ages of the participants were evenly distributed across the 2HPP CATEGORY age groups with a mean age of 38.2± 13.6 years (range 18–75 years). The majority of participants (74.8%) were educated up ABNORMAL NORMAL TOTAL to senior high/ordinary level (SHS/O level) and 68.2% were DEMOGRAPHIC 2 underweight. Males represented 78.9% of the study partici- CHARACTERISTICS N (%) N (%) N χ pants. The test of association suggests that 2HPP is associated Age group (years) 171 10.29* with only age group and educational level (P-value < .05). The 18 to 24 8 (22.2) 28 (77.8) 36 result shows that generally, the proportion of participants with abnormal 2HPP increases with age, the highest seen 25 to 34 13 (31.0) 29 (69.0) 42 among the middle-age group 45 to 54 (54.5%). Also, the pro- 35 to 44 15 (48.4) 16 (51.6) 31 portion of participants with dysglycemia with a low sputum 45 to 54 18 (54.5) 15 (45.5) 33 load was 19.4% compared to 20% in the case of normoglycemic patients whereas 80.6% and 79.8% of participants with high 55 to 64 13 (44.8) 16 (55.2) 29 sputum load were dysglycemic and normoglycemic, respect- Sex 171 0.65 ively. These marginal differences did not show any significant Male 55 (40.7) 80 (59.3) 135 differences. Full details of the demographic characteristics are shown in Table 1. Female 12 (33.3) 24 (66.7) 36 Marital status 171 1.24 3.2 Glycemic Variables of Participants Married 30 (40.0) 45(60.0) 75 Single 32 (36.8) 55 (63.2) 87 Of a total of 171 participants, using FPG values 87.1%, 8.8%, and 4.1% had normal glucose, impaired fasting, and diabetes, Separated/divorced 5 (55.6) 4 (44.4) 9 respectively. Using 2HPP values, 61.4%, 27.5%, and 11.1% Educational level 171 9.65* had normal glucose, impaired glucose tolerance, and diabetes, None 5 (33.3) 10 (66.7) 15 respectively. The combined prevalence of dysglycemia was thus 12.9% (n= 22) and 38.6% (n= 66) using fasting glucose Primary 6 (37.5) 10 (62.5) 16 and 2HPP values, respectively, as shown in Table 2. Middle/JHS 34 (54.0) 29 (46.0) 63 SHS/O level 14 (28.6) 35 (71.4) 49 3.3 Predictors of Abnormal Glucose Patterns Among Study Tertiary 8 (28.6) 20 (71.4) 28 Participants Employment status 170 1.79 Factors influencing the development of abnormal glucose were No 13 (30.2) 30 (69.8) 43 explored using binary logistic regression. Being aged 45 to 54 Yes 53 (41.7) 74 (58.3) 127 years had 6.43 increased odds (P-value= .007) for developing abnormal glucose compared to the reference age of 18 to 24 Smoking status 168 0.08 years. There were no other significant predictors of abnormal Yes 5 (35.7) 9 (64.3) 14 glucose values as shown in Table 3. No 61 (39.6) 93 (60.4) 154 Alcohol intake 167 0.77 3.4 Comparison of Sputum Conversion Rates at 2 and 6 Yes 9 (32.1) 19 (67.9) 28 Months No 57 (41.0) 82 (59.0) 139 The sputum status was assessed and compared to determine the sputum conversion rates at 2 and 6 months. At 2 months, a sig- BMI 157 1.78 nificantly higher proportion of normoglycemic subjects had Below 18.5 45(42.1) 62 (57.9) 107 negative sputum compared with those with dysglycemia (83% (underweight) vs 67%) (Z-test=−2.5; P < .05). Despite the proportionally 18.5 to 24.9(normal) 15 (33.3) 30 (66.7) 45 higher numbers of the dysglycemia group that maintained 25 to 29.9 (overweight) 1 (20.0) 4 (80.0) 5 sputum conversion at 6 months, there was no statistical differ- ence between the 2 groups (87% vs 77%, Z-test=−1.71, P > Systolic BP 170 0.88 .05), as shown in Table 4. (continued) 4 Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine Table 1. Continued. Table 3. Factors influencing abnormal glycaemia among TB patients 2HPP CATEGORY 95% CONF. INTERVAL ABNORMAL NORMAL TOTAL DEMOGRAPHIC COVARIATES AOR P-VALUE LOWER UPPER CHARACTERISTICS N (%) N (%) N χ2 Age group Normal 43 (39.8) 65 (60.2) 108 18 to 24 Ref Elevated 16 (34.0) 31 (66.0) 47 25 to 34 1.66 .398 0.51 5.38 Hypertension 7 (46.7) 8 (53.3) 15 35 to 44 3.27 .076 0.88 12.12 Diastolic BP 170 0.21 45 to 54 6.43 .007* 1.66 24.86 Normal 59 (39.3) 91 (60.7) 150 55 to 64 2.90 .144 0.70 12.11 Elevated 5 (33.3) 10 (66.7) 15 Sex Hypertension 2 (40.0) 3 (60.0) 5 Male Ref Waist–hip ratio 171 0.28 Female 0.80 .767 0.18 3.50 Low 55 (40.1) 82 (59.9) 137 Marital status Moderate 5 (35.7) 9 (64.3) 14 Married Ref High 7 (35.0) 13 (65.0) 20 Single 1.34 .504 0.57 3.19 Sputum load (2HPP) 171 0.016 Separated/divorced 1.10 .900 0.24 5.07 Low Load 13 (19.4) 21 (20.2) 34 Educational level High Load 54 (80.6) 83 (79.8) 137 None Ref *P< .05. Primary 1.66 .586 0.27 10.26 Abbreviations: 2HPP, 2-hour post-prandial glucose; TB, tuberculosis; BP, blood pressure; BMI, body mass index; SHS, senior high school; Middle/Junior High School 3.25 .125 0.72 14.68 Senior High School/O-level 1.08 .926 0.22 5.18 3.5 Predictors of Sputum Conversion at 2 and 6 Months Tertiary 1.02 .977 0.20 5.30 Binary logistic regression models were used to test the effect of Employment status sociodemographic, clinical, and lifestyle factors on the treat- ment (sputum conversion) (Table 5). After controlling for No Ref demographic factors and adjusting for age groups, the following Yes 2.26 .052 0.99 5.14 Smoking status Table 2. Glycaemic variables of study participants Yes Ref VARIABLE FREQUENCY (N ) PROPORTION (%) No 0.59 .460 0.14 2.40 Fasting Plasma Glucose (mmol/L) Alcohol intake (Mean±SD) 5.21± 1.46 Yes Ref Normal (<6.1) 149 87.1 No 0.56 .299 0.18 1.68 Impaired/borderline (6.1–7) 15 8.8 Systolic BP Diabetes (>7.1) 7 4.1 Normal Ref 2 HPP Glucose (mmol/L) Elevated 1.05 .901 0.47 2.37 (Mean±SD) 8.24± 3.26 Hypertension 1.41 .663 0.30 6.61 Normal (<6.1) 105 61.4 Diastolic BP Impaired/borderline (6.1–7) 47 27.5 Normal Ref Diabetes (>7.1) 19 11.1 (continued) Abbreviation: 2-HPP, 2-hour post-prandial glucose. Yorke et al. 5 Table 3. Continued. Table 5. 2HPP influence on treatment outcome (sputum conversion) among TB patients adjusting for demographic factors and controlling for 95% CONF. age group INTERVAL PERIOD OF TREATMENT OUTCOME COVARIATES AOR P-VALUE LOWER UPPER 2 MONTHS 6 MONTHS Elevated 0.42 .250 0.09 1.86 Hypertension 0.49 .517 0.06 4.26 Covariates AOR (95% CI) P-VALUE AOR (95% CI) P-VALUE Waist-to-hip ratio Two HPP Low Ref Normal Ref Ref Moderate 0.98 .978 0.18 5.17 Abnormal 0.34 (0.14–0.82) .018 0.46 (0.17–1.25) .128 High 0.90 .900 0.19 4.39 Sex *P< .05. Male Ref Ref Abbreviations: aOR, adjusted odds ratio; TB, tuberculosis; SHS/O level, senior high school/ordinary level. Female 7.44 (1.73–32.0) .007 9.29 (1.78–48.5) .008 Marital status Table 4. Test of proportion showing the differences in negative sputum Married Ref Ref test result between TB patients subjects with abnormal glucose and those with normal glucose (using 2HPP) at two and six months (n= 171) Single 1.47 (0.64–to 3.41) .363 1.75 (0.06–4.52) .249 2 MONTHS 6 MONTHS Separated/ 0.41 (0.08–1.91) .254 0.42 (0.06–2.81) .369 divorced 2 HPP PROPORTION (95% CI) PROPORTION (95% CI) Educational level Abnormal 67.16 (55.92–78.41) 77.61 (67.63–87.59) None Ref Ref Normal 83.65 (76.55–90.76) 87.5 (81.14–93.85) Primary 0.44 (0.08–2.49) .358 0.74 (0.08–6.46] .785 Z-statistic −2.51* −1.71 Middle/Junior 1.19 [(0.25–5.36) .826 3.82 (0.57–25.52) .166 High School *P-value< .05. Abbreviations: 2HPP, 2-hour post-prandial glucose; TB, tuberculosis Senior High 0.84 (0.18–3.82) .819 2.00 (0.33–12.14) .453 School/O-level Tertiary 0.72 (0.15–3.37) .679 0.72 (0.13–4.04) .713 factors were associated with sputum conversion at 2 months: subjects with dysglycemia were 66% less likely than those Employment status with normoglycemia (OR (adjusted odds ratio (aOR)), [95% No Ref Ref confidence interval (CI)], P-value: 0.34, [0.14–0.82], .018); Yes 1.27 (0.50–3.21) .619 0.22 (0.04–1.14) .072 females were 7.44 times more likely than men (aOR, [95% CI], P-value: 7.44, [1.73–32.0], .007); and those with high Smoking status WHR were 88% less likely compared with those with low Yes Ref Ref WHR (aOR, [95% CI], P-value: 0.12, [0.02–0.54], .006) to No 0.49 (0.08–2.91) .435 1.94 (0.31–12.27) .482 convert sputum, respectively. At 6 months and after similar adjustments, females (compared with males) and high WHR Alcohol intake (compared with those with normal WHR) were 9.29 times Yes Ref Ref more likely (aOR, [95% CI], P-value: 7.44, 9.29 [1.78–48.5], No 1.67 (0.50–5.58) .401 2.21 (0.26–5.57) .809 .008] and 89% less likely (aOR, [95% CI], P-value: 0.11, [0.02–0.63], .013) for sputum conversion, respectively. Waist-to-hip ratio Low Ref Ref Moderate 0.48 (0.09–2.44) .374 0.81 (0.11–5.95) .837 4. Discussion The results of the study show that at 2 months, a significantly High 0.12 (0.02–0054) .006 0.11 (0.02–0.63) .013 higher proportion of normoglycemic subjects had negative Abbreviations: 2HPP, 2-hour post-prandial glucose; aOR, adjusted odds ratio; sputum compared with those with dysglycemia. However, SHS, senior high school TB, tuberculosis 6 Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine despite the proportionally higher numbers of the normogly- include low incomes, the load of the bacilli, malnutrition, exces- cemia group that maintained sputum conversion at 6 months, sive alcohol use, overcrowding, smoking, HIV infection, dia- there was no statistical difference between the 2 groups. This betes, drugs that cause immunosuppression, and closeness to suggests a transient impact of dysglycemia on sputum conver- a person with active TB.1,5–36 sion among TB patients. While some studies have supported The increased risk of the age group 45–54 years with abnor- the negative impact of diabetes on sputum conversion through- mal blood glucose (aOR, 6.43) may represent an increased out the period of TB treatment, others have showed a transient inherent risk for dysglycemia and type 2 diabetes conferred by impact.9,11,12 Alisjahbana et al. reported that TB patients who increasing age.38 Subjects with high WHR were less likely to were diabetic had significantly higher percent of smear-positive convert sputum compared with those with normal WHR results than their nondiabetic counterparts at 2 months (18.1% both at 2 and 6 months. High WHR is a risk factor for dysgle- vs 10.0%). Unlike our study, after 6 months (end of the treat- mia and diabetes,39 which influences the development of ment), 22.2% of sputum specimens from diabetic patients reduced clearance of TB pathogens as described earlier were positive for M tuberculosis ( aOR, 7.65; P= .004).9 In a on.30,31 This association is also independent of age, family retrospective study that assessed TB patients with self-reported history of diabetes, and sex;39 the sex association is stronger diabetes from south Texas (USA) and north-eastern Mexico, in women than men.39 Central obesity as measured by para- the authors reported that TB patients were more likely to meters such as WHR, waist circumference (WC), and BMI remain positive at the end of the first (Texas cohort) or has been associated with impaired glucose–insulin homeostasis second (Mexico cohort) month of treatment,12 which was and insulin clearance, decreased insulin-stimulated glucose dis- similar to our study. A systematic review published in 2011 posal finally which leads to decreased glucose tolerance.40 by Baker et al. reported an increased risk of relapse in these It is not clear why females were more likely to convert patients (relative risk, 3.89; 95% CI, 2.43–6.23). Unlike our sputum than male counterparts both at 2 and 6 months. It study, some studies have however shown no relationship must, however, be stated that females are more likely than between diabetes and sputum conversion rate at the end of men to be compliant with their treatment and also keep their month 2,13,16,17 while a trend toward increased time to appointments, which may in turn improve treatment sputum conversion has rather been found in other outcomes.41,42 studies.15,26,27 The transient impact of dysglycemia on sputum conversion 5. Conclusion rate suggests possible nonlasting pathophysiological linkages 28,29 This study has added to the body of knowledge on the impact ofand putative mechanisms. The risk of TB patients with dysglycemia on sputum conversion among TB patients. A sig- diabetes for reduced sputum conversion rate is suggested puta- nificantly lower proportion of smear-positive TB patients with tively due to the reduced numbers as well as the function of T dysglycemia converted to smear negative after 2 months of lymphocytes involved in T-helper cells 1(TH1) cytokine inhib- 30,31 treatment but not at the end of treatment suggesting a transientition of M tuberculosis. In diabetes, dysfunction of macro- impact of dysglycemia on sputum conversion. Other factors, phages occurs, which impairs phagocytic and chemotactic including age, female sex, and increased WHR, have shown function as well as the production of reactive oxygen 30,31 association. Larger studies are needed to validate these findings.species. Further, the impairment of chemotaxis of mono- A change in the current TB regimen is not recommended based cytes is thought to occur in diabetes.32 The respiratory burst on our findings. used in expelling pathogens is also thought to be impaired 30,31 Future research is required in this field and must comparewith diabetes. the severity of TB presentation between the dysglycemia and TB on its own has been linked to the development of 28,33 normoglycemic groups, such as symptom burden, pattern ofimpaired glucose tolerance (IGT) and new-onset dia- 28,34 lobe involvement, reactivation of old foci, rates of hemoptysis,betes. While IGT generally normalizes after TB has been fever, and atypical presentations and cavitations. We plan to treated, the risk of developing type 2 diabetes in the future 35 perform formal glucose tolerance tests at 2 months (end ofremains high. Some other studies revealed that between the intensive phase) and at 6 months (end of the treatment) 19% to 42.6% of active TB patients, who were discovered to to confirm whether dysglycemia associated with TB is transient. have IGT or diabetes, had significant reduction or complete Patients would also be followed up to ascertain the RRs regression in the rates after treatment.28,29 This suggested between the two groups. stress response to infection leading to dysglycemia is thought to be due to the elaboration of interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha.5,35 Acknowledgments Unsurprisingly in our study, most participants were young, We also appreciate the contribution of Ama Aidoo, Norah male, and single; those are well-known sociodemographic char- Nkornu, and Kelvin Acquaye, especially in data collection. acteristics of TB patients.1,36,37 Other risk factors for TB Data Availability Statement Yorke et al. 7 The data that support the findings of this study are available 14. Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis. 2009;9(12):737–746. from the corresponding author upon request 15. Gautam S, Shrestha N, Mahato S, Nguyen TP, Mishra SR, Berg-Beckhoff G. Diabetes among tuberculosis patients and its impact on tuberculosis treatment in South Asia: a systematic review and meta-analysis. Sci Rep. 2021;11(1):1–12. Author Contributions 16. Kameda K, Kawabata S, Masuda N. Follow-up study of short course chemotherapy EY conceived the study, participated in its design, data collec- for pulmonary tuberculosis complicated with diabetes mellitus. Kekkaku tion, analysis, and drafted the manuscript and collation of all (Tuberculosis). 1990;65(12):791–803.17. Singla R, Khan N, Al-Sharif N, Al-Sayegh MO, Shaikh MA, Osman MM. drafts. VB, IDD, VG, MBAM, EKA, JT, and CCM contrib- Influence of diabetes on manifestations and treatment outcome of pulmonary TB uted to the study design, data collection, analysis, and writing patients. Int J Tuberc Lung Dis. 2006;10(1):74–79. 18. Cheng J, Zhang H, Zhao YL, Wang LX, Chen MT. Mutual impact of diabetes the manuscript draft. All authors read and approved the final mellitus and tuberculosis in China. Biomed Environ Sci. 2017;30(5):384–389. version of the manuscript. 19. Chiang CY, Bai KJ, Lin HH, et al. The influence of diabetes, glycemic control, and diabetes-related comorbidities on pulmonary tuberculosis. PloS one. 2015;10(3): e0121698 Ethical Approval and Consent to Participate 20. Morsy AM, Zaher HH, Hassan MH, Shouman A. Predictors of treatment failure among tuberculosis patients under DOTS strategy in Egypt. East Mediterr Health Ethical and Protocol approval for the study was sought from the J. 2003 Jul;9(4):689–701. College of Health Sciences Ethics and Protocol Review 21. Jiménez-Corona ME, Cruz-Hervert LP, García-García L, et al. Association of dia- betes and tuberculosis: impact on treatment and post-treatment outcomes. Thorax. Committee of the University of Ghana with reference 2013;68(3):214–220. number URF/9/ILG-076/2015 to 2016. It complied with the 22. Singla R, Osman M, Khan N, Al-Sharif N, Al-Sayegh M, Shaikh M. Factors pre- dicting persistent sputum smear positivity among pulmonary tuberculosis patients 2 Helsinki Declaration of 1964 (Revised 2013) on human experi- months after treatment. Int J Tuberc Lung Dis. 2003;7(1):58–64. mentation. All patients provided written informed consent. 23. Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Strict con dentiality of data and privacy for study participants Guidelines and recommendations for laboratory analysis in the diagnosis and man-fi agement of diabetes mellitus. Clin Chem. 2002;48(3):436–472. were ensured. Data were kept secured and available only to 24. World Health Organization. International Diabetes Federation (2006) Definition the principal investigator. and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. IDF Consultation; 2008. 25. Alberti G, Zimmet P, Shaw J, Grundy SM. The IDF consensus worldwide defin- ORCID iD ition of the metabolic syndrome. Brussels: Int Diabetes Fed. 2006;23(5):469–480.26. Heysell SK, Moore JL, Keller SJ, Houpt ER. Therapeutic drug monitoring for slow Ernest Yorke https://orcid.org/0000-0003-4257-7492 response to tuberculosis treatment in a state control program, Virginia, USA. Emerg Infect Dis. 2010;16(10):1546. 27. Chang J-T, Dou H-Y, Yen C-L, et al. Effect of type 2 diabetes mellitus on the clin- Trial Registration ical severity and treatment outcome in patients with pulmonary tuberculosis: a poten- Not applicable, as no trial was conducted. tial role in the emergence of multidrug-resistance. J Formos Med Assoc.2011;110(6):372–381. 28. Basoglu OK, Bacakoglu F, Cok G, Saymer A, Ates M. The oral glucose tolerance test in patients with respiratory infections. Monaldi Arch Chest Dis. REFERENCES 1999;54(4):307–310. 1. WHO. Global Tuberculosis Report 2017. World Health Organization; 2017. 29. Oluboyo PO, Erasmus RT. The significance of glucose intolerance in pulmonary 2. Young F, Wotton CJ, Critchley JA, Unwin NC, Goldacre MJ. Increased risk of tuberculosis. Tubercle. 1990;71(2):135–138. tuberculosis disease in people with diabetes mellitus: record-linkage study in a UK 30. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes melli- population. J Epidemiol Community Health. 2010;66(6):519-523. doi:10.1136/jech. tus (DM). FEMS Immunol Med Microbiol. 1999;26(3-4):259–265. 2010.114595 31. Tsukaguchi K, Yoneda T, Yoshikawa M, et al. Case study of interleukin-1 beta, 3. Yorke E, Atiase Y, Akpalu J, Sarfo-Kantanka O, Boima V, Dey ID. The bidirec- tumor necrosis factor alpha and interleukin-6 production peripheral blood mono- tional relationship between Tuberculosis and diabetes. Tuberc Res Treat. cytes in patients with diabetes mellitus complicated by pulmonary tuberculosis. 2017;6:1702578. doi:10.1155/2017/1702578 Kekkaku. 1992;67(12):755–760. 4. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence esti- 32. Moutschen MP, Scheen AJ, Lefebvre PJ. Impaired immune responses in diabetes mates for 2019 and projections for 2030 and 2045: Results from the International mellitus: analysis of the factors and mechanisms involved. Relevance to the increased Diabetes Federation Diabetes Atlas, 9th edition. DRCP. 2019;157(107843):1-10. susceptibility of diabetic patients to specific infections. Diabete Metab. 1992;18- 5. Niazi AK, Kalra S. Diabetes and tuberculosis: a review of the role of optimal gly- (3):187–201. cemic control. J Diabetes Metab Disord. 2012;11(1):2251–6581. 33. Jeon CY, Harries AD, Baker MA, et al. Bi-directional screening for tuberculosis and 6. Stevenson CR, Critchley JA, Forouhi NG, et al. Diabetes and the risk of tubercu- diabetes: a systematic review. Research support, Non-US Govt review. Trop Med Int losis: a neglected threat to public health? Chronic Illn. 2007;3(3):228–245. Health. 2010;15(11):1300–1314. 7. Pealing L, Wing K, Mathur R, Prieto-Merino D, Smeeth L, Moore DAJ. Risk of 34. Mugusi F, Swai AB, Alberti KG, McLarty DG. Increased prevalence of diabetes tuberculosis in patients with diabetes: population based cohort study using the UK mellitus in patients with pulmonary tuberculosis in Tanzania. Tubercle. 1990;71- clinical practice research datalink. BMC Med. 2015;13(1):1–16. (4):271–276. 8. Noubiap JJ, Nansseu JR, Nyaga UF, et al. Global prevalence of diabetes in active 35. Amrit G, Ashok S. Tuberculosis and diabetes: an appraisal. Indian J Tuberc. tuberculosis: a systematic review and meta-analysis of data from 2·to 3 million 2000;47(1):3–8. patients with tuberculosis. Lancet Glob Health. 2019;7(4):e448–e460. 36. Amare H, Gelaw A, Anagaw B, Gelaw B. Smear positive pulmonary tuberculosis 9. Alisjahbana B, Sahiratmadja E, Nelwan EJ, et al. The effect of type 2 diabetes mel- among diabetic patients at the Dessie referral hospital, northeast Ethiopia. Infect litus on the presentation and treatment response of pulmonary tuberculosis. Clin Dis Poverty. 2013;2(1):6. Infect Dis. 2007;45(4):428–435. 37. Narasimhan P, Wood J, MacIntyre CR, Mathai D. Risk factors for tuberculosis. 10. Wilson RM. Infection and diabetes mellitus. In: Pickup JC, Williams G, eds. Pulm Med. 2013;2013. doi: 10.1155/2013/828939 Textbook of Diabetes. Blackwell Scientific Publication; 1991:813–819. 38. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care. 11. Baker MA, Harries AD, Jeon CY, et al. The impact of diabetes on tuberculosis treat- 2012;35(12):2650–2664. doi:10.2337/dc12-1801 ment outcomes: a systematic review. BMC Med. 2011;9(81):1741–7015. 39. Schmidt MI, Duncan BB, Canani LH, Karohl C, Chambless L. Association of 12. Restrepo BI, Fisher-Hoch SP, Crespo JG, et al. Type 2 diabetes and tuberculosis in a waist-hip ratio with diabetes mellitus: strength and possible modifiers. Diabetes dynamic bi-national border population. Epidemiol Infect. 2007;135(3):483–491. Care. 1992;15(7):912–914. 13. Dooley KE, Tang T, Golub JE, Dorman SE, CroninW. Impact of diabetes mellitus 40. Vazquez G, Duval S, Jacobs Jr DR, Silventoinen K. Comparison of body mass index, on treatment outcomes of patients with active tuberculosis. Am J Trop Med Hyg. waist circumference, and waist/hip ratio in predicting incident diabetes: a 2009;80(4):634–639. meta-analysis. Epidemiol Rev. 2007;29(1):115–128. 8 Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 41. Manteuffel M, Williams S, Chen W, Verbrugge RR, Pittman DG, Steinkellner A. United Kingdom. He has been extensively involved in the organization Influence of patient sex and gender on medication use, adherence, and prescribing and also served as a facilitator to numerous metabolic and cardiovascular alignment with guidelines. J Womens Health. Feb 2014;23(2):112–119. doi:10. 1089/jwh.2012.3972 Continuing Medical Education programs, both locally and abroad. He 42. Rodriguez Pacheco R, Negro Alvarez JM, Campuzano Lopez FJ, et al. values the use of practical tools as well as new technology in research Non-compliance with appointments amongst patients attending an allergology and development to solve problems and also to advance knowledge. clinic, after implementation of an improvement plan. Allergol Immunopathol He has served as a consultant and Advisory Board member for a (Madr). Jul-Aug 2007;35(4):136–144. number of multinational pharmaceutical companies involved in dia- betes care, both locally and abroad. His main research interests Author Biography include diabetes and kidney disease, psychological impact of diabetes, pregnancy outcomes in diabetes, and diabetic foot care as well as Ernest Yorke, FWACP, FGCP, MSc, Diabetes (Cardiff), MSc, thyroid diseases. He has over 30 peer-reviewed publications to his Endo. (UK), MB ChB, BSc, Cert. HAM (Ghana Institute of credit. He has other interests outside clinical work and academia. Management and Public Administration, GIMPA). Dr Ernest Among many other volunteer works, he is currently the Chairman of Yorke is a fellow of the West African College of Physicians and the the Greater Accra Division of the Ghana Medical Association and Ghana College of Physicians & Surgeons. Currently, he is a senior lec- also a Board member of Diabetes Youth Care, a non-governmental turer at the University of Ghana Medicine School, and a consultant organization dedicated to the care and well-being of young people physician/endocrinologist at the Korle-Bu Teaching Hospital, Accra. living with diabetes in Ghana. He is married with three children and He also holds double Masters’ degrees from universities from the watches TV in his spare time.