|Year : 2019 | Volume
| Issue : 1 | Page : 217-220
Study of serum leptin in patients with active pulmonary tuberculosis
Osama F Mansour1, Ahmed A Khames1, Esam El-Din I. Radwan2, Maha Yousif1, Mai M. A. Elkhatib1
1 Department of Chest, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
|Date of Submission||01-Aug-2017|
|Date of Acceptance||08-Oct-2017|
|Date of Web Publication||17-Apr-2019|
Mai M. A. Elkhatib
El-Mahalla El-Kobra El-Gharbia
Source of Support: None, Conflict of Interest: None
To assess the level of serum leptin in patients with active pulmonary tuberculosis (TB).
One of the most important and common complaint of patients with TB, which also affects the immune status, is weight loss. When TB infection occurs, a variety of chemokines and cytokines are secreted from infected cells and tissue macrophages. Leptin is a 16-kDa protein, and its level varies with active pulmonary TB.
Patients and methods
Serum leptin level was measured in 40 newly diagnosed patients with active pulmonary TB (group I) and 20 matched control (group II).
Serum leptin level was significantly lower in patients with active pulmonary TB than controls. There was a highly significant positive correlation between leptin level and BMI. Serum leptin had a significantly negative correlation with grades of Ziehl–Neelsen stain and chest radiography. The cutoff point of leptin was found to be 0.54 ng/ml for discrimination of patients with active pulmonary TB.
Serum leptin hormone level was lower in patients with tuberculosis than in controls, which indicates that leptin plays a role in diminishing appetite, weight loss, and increasing susceptibility to infection.
Keywords: active tuberculosis, chest radiography, loss of weight, leptin, Ziehl–Neelsen stain
|How to cite this article:|
Mansour OF, Khames AA, I. Radwan EE, Yousif M, Elkhatib MM. Study of serum leptin in patients with active pulmonary tuberculosis. Menoufia Med J 2019;32:217-20
|How to cite this URL:|
Mansour OF, Khames AA, I. Radwan EE, Yousif M, Elkhatib MM. Study of serum leptin in patients with active pulmonary tuberculosis. Menoufia Med J [serial online] 2019 [cited 2019 May 21];32:217-20. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/217/256122
| Introduction|| |
Tuberculosis (TB) is a major cause of death around the world. One of the most important and common complaint of patients with tuberculosis, which also affects the immune status, is weight loss. Antimycobacterial treatment often increases weight, but patients may remain underweight even after 6 months of successful chemotherapy .
When TB infection occurs, a variety of chemokines and cytokines are secreted from infected cells and tissue macrophages. Leptin, a 16-kDa protein encoded by the obese gene, is mainly produced by adipocytes .
It is known to have a strong positive correlation with BMI, which increases when one is overweight and decreases in cases of wasting. Leptin is shown to modulate immune response and favor a Th1 response, whereas it inhibits the secretion of Th2 cytokines .
Studies done in patients with pulmonary TB have also reported low serum leptin levels and lack of significant correlation between serum proinflammatory cytokines and leptin levels .
On the contrary, some studies have reported conflicting data, with elevated serum leptin levels in patients with TB .
Therefore, the aim of this work is to investigate the relationship between serum leptin levels and TB.
| Patients and Methods|| |
This study was carried out in El-Mahala Chest Hospital, Menoufia University hospital, during the period from April 2014 to September 2015. A total of 60 patients were included in the study: 40 newly diagnosed patients with active pulmonary TB and 20 age-matched and sex-matched individuals who served as a control group. After obtaining an informed consent from each one of them, they underwent the following:
Medical history taking.
Clinical (general and chest) examination: BMI [weight (kg)/height (m 2)]; BMI categories: underweight, less than 18.5; normal weight, 18.5–24.9; overweight, 25–29.9; and obesity, BMI of 30 or greater .
Radiological examination: plain chest radiography.
Mycobacteriological investigations: sputum smears examination by Zeil–Nelseen (ZN) stain.
Laboratory investigations: complete blood picture, erythrocyte sedimentation rate, fasting serum glucose level and 2 h postprandial glucose level, kidney functions (urea and creatinine clearance), liver functions (alanine transaminase, aspartate aminotransferase, and serum albumin), and serum leptin level measured by enzyme-linked immunosorbent assay technique (DRG Instruments GmbH Division of DRG International Inc., Marburg, Germany) .
Data were collected, tabulated, and statistically analyzed using SPSS 20 for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for windows (MedCalc Software BVBA, Ostend, Belgium), and the following statistics were applied.
Descriptive statistics were stated as mean and SD. Analytical statistics used the following tests of significance: χ2 was used to study association between two qualitative variables, Student's t-test is a test of significance used for comparison between two groups having quantitative variables, and Pearson's correlation (r) is a test used to measure the association between two quantitative variables. The receiver operating characteristic curve is a procedure used to evaluate the performance of classification schemes in which there is one variable of two categories by which participants are classified.
P value of less than 0.05 was considered statistically significant, and P value of less than 0.001 was considered statistically highly significant.
| Results|| |
Patients and controls were compared regarding BMI, leptin level, and positivity of sputum by ZN (P < 0.05). Mean BMI of patients with TB was 22.33 ± 4.05 kg/m 2 and that of the control group was 26.8 ± 4.02 kg/m 2. BMI was significantly lower in group I compared with group II. Serum leptin level of patients with tuberculosis was 2.29 ± 12.5 ng/ml, whereas that of controls was 9.3 ± 12.5 ng/ml. There was significant lower serum leptin level in group I when compared with group II (P < 0.05) [Table 1]. There was a highly significant difference within group I according to positivity of sputum ZN stain: 12.5% of the patients had more than 10 TB bacilli, 17.5% of the patients had positive (+) sputum smear, 55% patients had double positive (++) sputum smear, and 15% patients had triple positive (+++) sputum smear. There was a highly significant difference between these subgroups (P > 0.001) [Table 2].
|Table 1: Comparison between the studied groups regarding BMI and serum leptin|
Click here to view
|Table 2: Distribution of sputum positivity in the studied patients and receiver operating characteristic curve for diagnostic validity of serum leptin in cases of active pulmonary tuberculosis|
Click here to view
The optimal discrimination of patients with active pulmonary TB could be performed at a cutoff point of serum leptin level of 0.54 ng/ml with sensitivity 80%, specificity 89%, positive predictive value 73%, negative predictive value 93%, diagnostic accuracy 87%, and area under the curve 0.788 [Table 2].
Serum leptin level was highly positively correlated with BMI (P < 0.001) and was negatively correlated with ZN stain and chest radiography (CXR) (P < 0.05) [Table 3].
|Table 3: Spearman's correlation between leptin and (BMI, Ziehl-Neelsen stain, and chest radiography)|
Click here to view
| Discussion|| |
In the current study, the mean ± SD BMI was 22.33 ± 4.05 kg/m 2 in patients, 26.8 ± 4.02 kg/m 2 in controls, with statistically significant difference between them.
This result was in agreement with Tverdal  and Lee et al.  who described that BMI was significantly lower in patients when compared with controls. There was a strong and consistent log-linear inverse relationship between TB incidence and BMI across a variety of settings with different levels of TB burden .
In this work, the mean value of serum leptin was 2.29 ± 12.5 ng/ml in patients and 9.3 ± 12.5 ng/ml in controls, with statistically significant difference between them.
These results agreed with van Crevel et al. , Buyukoglan et al. , and Schwenk et al.  who reported that plasma leptin concentrations were significantly suppressed in patients with TB in Indonesia and hypothesized decreased leptin levels in patients with TB. On the contrary, Cakir et al. , Kim et al. , and Yuksel et al.  declared increase in leptin levels in patients with TB, whereas other studies reported no changes in serum leptin in active TB and it had no role in loss of weight in active TB .
According to positivity of sputum ZN stain, 12.5% of the patients has more than 10 TB bacilli/field, 17.5% of the patients has 1+ sputum smear, 55% patients has 2+ sputum smear, and 15% patients has 3+ sputum smear, with a highly significant difference between these subgroups (P > 0.001).
These results partially agreed with Bawri et al. , who reported that there were 11 (22%) patients who had grade +3 sputum smear, 20 (40%) patients had grade +2 sputum smear, 18 (36%) patients had grade +1 sputum smear, and one (2%) patient had scanty sputum smear (1–9 AFB in 100 fields). Rajpal et al. , reported that 15 (5.2%) patient had scanty sputum smear, 80 (27.7%) patients had grade +1 sputum smear, 55 (19.0%) patients had grade +2 sputum smear, and 138 (47.9%) patients had grade +3 sputum smear. On the contrary, Agha et al. , reported 131 543 cases with grade + 1, grade + 2, grade + 3 respectively from 85 patients with TB.
To discriminate between low, normal, and high leptin levels in patients with active pulmonary TB and controls, we calculated cutoff points using receiver operating characteristic analysis for serum leptin level [Figure 1]. The cutoff point of serum leptin as a potential method for differential diagnosis between healthy group and TB group was found to be 0.54 ng/ml, with sensitivity 80%, specificity 89%, positive predictive value 73%, negative predictive value 93%, diagnostic accuracy 87% and area under the curve 0.788.
|Figure 1: Receiver operating characteristic (ROC) curve for diagnostic validity of serum leptin in cases of active pulmonary tuberculosis.|
Click here to view
In a study by Celik et al. , the cutoff point of serum leptin was found to be 3.25 ng/ml, with sensitivity 64%, specificity 47%, and area under the curve 0.717, whereas in the study by Du et al. , leptin at cutoff value of 1.2 ng/ml had an area under the curve, sensitivity, and specificity of 0.763, 88.3, and 65.8%, respectively. These differences among studies may be explained by the differences in the number of samples, method of detection, and preparation of samples.
In this study, there was a highly significant positive correlation between serum leptin and BMI. In accordance to our finding, numerous studies reported a positive correlation between leptin and BMI in the active-disease group . They found that being underweight could suppress lymphocyte stimulation and reduce Th1 cytokine secretions (as leptin), the loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active TB may contribute to increased disease severity, especially in patients with cachexia . This agreed with Ghantous et al. , who concluded that the obesity is associated with high levels of the circulating hormone leptin, and they thought that leptin is responsible for several cardiovascular diseases associated with obesity, as serum leptin levels was very low in patients with active TB with low BMI (whereas leptin levels were higher in the latent TB and control groups, as their BMI was elevated); they explained this by glucocorticoids and insulin act on adipocytes to increase leptin expression in obese, possibly explaining the reason for increased leptin levels observed in obesity. However, Yüksel et al.  stated that increasing leptin level has a role in diminishing appetite and weight loss symptoms in patients with active lung TB.
Elnemr et al.  stated that plasma leptin concentrations in TB may be the result of two antagonistic mechanisms: although TB-associated loss of body fat mass may lead to reduced production of leptin, the host inflammatory response may increase leptin production, and if, as an overall result, plasma leptin concentrations are increased in patients with TB, then this might theoretically suppress appetite and food intake and be one of the mechanisms underlying weight loss, but if plasma leptin concentrations are decreased in TB, then this might suppress cellular immunity and aggravate disease outcome .
The current study matched the results of Sanchez-Margalet and colleagues, in that serum leptin had a significantly negative correlation with grades of Ziehl–Neelsen (ZN) stain and matches the results of a Buyukoglan and colleagues, Van Crevel et al. , and Keicho and colleagues, in that serum leptin had a significantly negative correlation with CXR findings. Both grades of ZN stain and CXR findings reflect the degree of infectivity and disease severity in pulmonary TB, and it had been previously hypothesized that serum leptin was decreased in TB proportionately to the degree of inflammatory response that suppressed leptin production .
| Conclusion|| |
Leptin levels are suppressed in patients with tuberculosis compared with controls. There was a highly significant positive correlation between leptin level and BMI, whereas serum leptin level had a significantly negative correlation with grades of ZN stain and CXR. The cutoff point of leptin was found to be 0.54 ng/ml.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Flynn JL, Chan J, Macallan DC. Immunology of tuberculosis. Ann Rev Immunol 2001; 19
Buyukoglan H, Gulmez I, Kelestimur F, Kart L, Oymak FS, Demir R, et al
. Leptin levels in various manifestations of pulmonary tuberculosis. Mediators Inflamm 2007; 2007
Schwenk A, Hodgson L, Rayner CF, Griffin GE, Macallan DC. Leptin and energy metabolism in pulmonary tuberculosis. Am J Clin Nutr 2003; 77
Çakır B, Yönem A, Güler S, Odabaşı E, Demirbaş B, Gürsoy G, et al
. Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis. Horm Res 1999; 52
Gallagher D, Visser M, Sepulveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol 1996; 143
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al
. Serum immune reactive-leptin concentrations in normal weight and obese humans. N Engl J Med 1996; 334:292–295.
Tverdal A. Body mass index and incidence of tuberculosis. Eur J Respir Dis 1986; 69
Lee JY, Lee KS, Jung KJ, Han J, Kwon OJ, Kim J, et al
. Pulmonary tuberculosis: CT and pathologic correlation. J Comput Assist Tomogr 2000; 24
Lönnroth K, Williams BG, Cegielski P, Dye C. A consistent log-linear relationship between tuberculosis incidence and body mass index. Int J Epidemiol 2010; 39
Van Crevel R, Karyadi E, Netea MG, Verhoef H, Nelwan RH, West CE, et al
. Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation. J Clin Endocrinol Metab 2002; 87
Kim JH, Lee CT, Yoon HI, Song J, Shin WG, Lee JH, et al
. Relation of ghrelin, leptin and inflammatory markers to nutritional status in active pulmonary tuberculosis. Clin Nutr 2010; 29
Yüksel İ, Şencan M, SebilaDökmetaş H, Dökmetaş İ, Ataseven H, Yönem Ö. The relation between serum leptin levels and body fat mass in patients with active lung tuberculosis. Endocr Res 2003; 29
Lönnroth K, Jaramillo E, Williams BG, Dye C, Raviglione M. Drivers of tuberculosis epidemics: the role of risk factors and social determinants. Soc Sci Med 2009; 68
Bawri S, Ali S, Phukan C, Tayal B, Baruwa P. A study of sputum conversion in new smear positive pulmonary tuberculosis cases at the monthly intervals of 1st
month under directly observed treatment, short course (dots) regimen. Lung India 2008; 25
Rajpal S, Dhingra VK, Aggarwal JK. Sputum grading as predictor of treatment outcome in pulmonary tuberculosis. Indian J Tuberc 2002; 49
Agha MA, El-Helbawy RH, El-Helbawy NG, El-Sheak NM. Utility of quantitative analysis of urine lipoarabinomannan in the diagnosis of tuberculosis. Egypt J Chest Dis Tuberc 2013; 62
Celik GA, Kaya B, Poyraz A, Ciledag AH, Elhan A, Oektem E, et al
. Diagnostic value of leptin in tuberculous pleural effusions. Int J Clin Pract 2006; 60
Du SS, Zhao MM, Zhang Y, Zhang P, Hu Y, Wang LS, et al
. Screening for differentially expressed proteins relevant to the differential diagnosis of sarcoidosis and tuberculosis. PLoS One 2015; 10
Keicho N, Matsushita I, Tanaka T, Shimbo T, Le Hang NT, Sakurada S, et al
. Circulating levels of adiponectin, leptin, fetuin-A and retinol-binding protein in patients with tuberculosis: markers of metabolism and inflammation. PLoS One 2012; 7
Elnemr GM, Elnashar MA, Elmargoushy NM, Elnashar NA, Elnashar MA. Adiponectin levels as a marker of inflammation in pulmonary tuberculosis. Egypt J Hospital Med 2015; 59
Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol 2015; 2015
[Table 1], [Table 2], [Table 3]