Highlights
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The dual burden of TB and DM increases the risk of disease severity and impact on morbidity and mortality rate.
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Malnutrition in patients with TB and/or DM is a contributing factor in worsening the condition.
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Majority of patients in TB-DM group presented higher HbA1c indicative of potential role of TB in poor glycemic control.
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The prevalence of vitamin D deficiency (VDD) was higher in TB-DM group.
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Detection of nutritional deficiency and rectification by the supplements with ATT and hypoglycemic drugs is warranted.
Keywords: Malnutrition, Tuberculosis, Diabetes Mellitus, Nutritional status, Deficiency
Abstract
Background
India has been estimated to have 14 % of malnourished population and a high TB incidence burden with a 26.9 lakh cases. Malnutrition and diabetes mellitus are major risk factors for tuberculosis infection. Malnutrition in patients with both tuberculosis and diabetes (TB-DM) population worsens the disease severity, treatment outcomes and increases morbidity and mortality risk.
Objective
To assess the nutritional status in patients with TB-DM compared with patients with TB and DM alone.
Method
Records from January 2016 to November 2020 for patients admitted to Kasturba Hospital, Manipal were assessed. Data pertaining to glycemic parameters, nutritional parameters, and other relevant laboratory parameters were extracted for assessment. The study population were divided into three groups i.e. patients with TB-DM, TB and DM. The statistical association was carried out with one-way ANOVA method, considering p < 0.05 as statistically significant.
Results
A total of 291 patients were included, with 97 patients in each group; among those, male and female were 86.27 % and 13.73 % respectively. Cardiovascular co-morbidity was predominant in the DM (68.04 %) and TB-DM (26.8 %) group. The mean value of HbA1c (10.47 %) was found to be highest for the TB-DM group. Low levels of albumin were reported by 71.91 % of patients of the TB group, whereas 73.68 % patients in TB-DM group had vitamin D deficiency. Moreover, higher prevalence of low MCV and MCH in the TB-DM group suggest an increased risk of iron-deficiency anemia.
Conclusion
The findings of our study reflect the need for implementation of nutritional support in patients with TB-DM.
1. Introduction
Malnutrition in tuberculosis (TB) and diabetes mellitus (DM) have been recognized as well-established high-risk factors. Although the link between malnutrition and TB and DM have been recognized long back, it remains unaddressed and highly prevalent risk-factor in developing countries. The current data shows an estimated 10.6 million people fell ill with TB in 2021. Diabetes mellitus is reported to be among the top five attributable risk factors for number of TB cases globally [1]. From global estimates for diabetes prevalence, it has been projected to increase by 25 % and 51 % by 2030 and 2045 respectively [2]. According to WHO, 0.35 million TB cases were attributed to DM [3]. Globally, India holds the first rank in TB and second rank in DM prevalence [4]. The global nutrition report states around 33 % of the population is overweight, while the percentage of underweight is ten times higher in poorer countries [5]. India is among 88 countries being off-track from achieving global nutrition targets by 2025. According to the global nutrition report, the prevalence of stunting in children under five years of age is recorded as 37.9 %, whereas wasting is recorded as 20.8 % in India [5].
Among all the risk factors, malnutrition and DM are recognized as serious risk factors for worsening TB prognosis. Undernutrition provokes the weakening of the immune system and increases the mortality rate. Therefore, DM along with undernutrition increases the chances of TB infection and progression [6], [7]. To understand the causal relationship between malnutrition and mortality in TB patients, Zachariah et al. reported that 10.9 % TB patients with moderate-to-severe malnutrition (BMI < 17 kg/m2) died within first four weeks [8]. Moreover, malnutrition increases the risk of hypoglycemia, increasing the risk of disease severity, mortality, and morbidity [9], [10]. In all, nutritional status is a key contributing factor, especially in patients with dual burden of TB and DM.
Nutritional supplementation in patients with active TB receiving anti-tubercular drug therapy (ATT) has been found to be effective in improving clinical outcomes. Micronutrients such as zinc, vitamin A, D, E, C, and iron improves immune response in TB patients [11]. Vitamin A deficiency was responsible for increased bacterial adherence to respiratory epithelial cells [12]. A study conducted in Indonesia indicated that the prevalence of anemia and low concentrations of retinol, zinc, iron, and hemoglobin (Hb) was higher in malnourished TB patients [13]. The risk factors for increased undernutrition may include low food frequency, diabetes, HIV infection [14]. India, under the sustainable development goals (SDGs) of reducing TB incidence and mortality up to 90 % by 2035, targets to end all forms of malnutrition by 2030 [15]. Hence, the present study will provide insights, from a tertiary hospital-based perspective, the nutritional status among patients with TB-DM as compared to patients with TB and DM alone.
2. Methods
2.1. Study design
This study is a retrospective case-control study for comparing nutritional status among TB-DM and TB and DM groups.
2.2. Study settings
The study was conducted at a tertiary care hospital, Kasturba Hospital, Manipal, Karnataka, India.
2.3. Sample size calculation
The sample size was calculated based on two proportion hypothesis testing methods with equal allocation for a large proportion. Considering 30 % of TB-DM among TB patients, 5 % level of significance, and 80 % power, the required sample size is 23. Assuming 25 % of patient's files will be incomplete, the total required sample size was 33. Since we received 97 cases of TB-DM patients, 97 cases were also included in TB and DM groups using similar age and gender criteria.
2.4. Study population
The study included patients with TB, DM, TB-DM admitted to the hospital from January 2016 to November 2020. The study inclusion criteria were: 1) patients with TB, DM, TB-DM, 2) age between 18 and 80 years with no gender restrictions. We also included patients with extra pulmonary TB (EPTB), multidrug resistance (MDR) TB, extended drug resistance (XDR) TB, and co-morbidities such as HIV, cardiovascular diseases. We excluded patients <18 and >80 years of age. We divided the patients into three groups according to the diseased condition: TB-DM (group-1), TB only (group-2), and DM only (group-3). A total of 291 patients were included in the study, with 97 in each group. Patients were considered a case of TB if they had positive sputum microscopy for acid-fast bacilli (AFB) or MTB detected by GeneXpert test or chest x-ray suggestive of TB.
2.5. Data collection
The data was collected in preformed data extraction form in Microsoft Excel 2019 version 16.06. Data such as age, gender, co-morbidities, family history for TB and DM, medical history, smoking, and alcohol status were extracted for patient characteristics. Additionally, the laboratory parameters such as hematological (Hb, WBC, MCV, MCH, neutrophil), nutritional (albumin, globulin, ferritin, folate, vitamin D, vitamin B12) and glycemic (HbA1c, FBS, RBS, PPBS) parameters were collected since which reflects nutritional and health status of TB and DM patients. A detailed description of the study process is shown in Fig. 1.
Fig. 1.
The study flow-chart.
2.6. Data analysis
The data analysis was performed in Excel and SPSS software. All the laboratory parameters were compared between the three groups taking TB-DM as case group and TB only and DM only as the control group. The result was recorded in mean ± SD (standard deviation). Multiple logistic regression model- One-way ANOVA was performed for determining the statistical association between the groups using SPSS 20.0. The results were recorded in mean difference, standard error with 95 % confidence interval, and considering p < 0.05 as statistically significant. Further, we plotted graphs for statistically significant parameters using GraphPad Prism version 9.0.2.
2.7. Ethical approval
The study was approved by the institutional ethics committee, Kasturba Medical College, and Kasturba Hospital, Manipal (IEC number: 222/2021).
3. Results
3.1. Patient characteristics
The records were screened as per the inclusion and exclusion criteria. Demographic characteristics of the patients are shown in Table 1. The mean age was found to be 51.84 ± 10.85 for total study population. Among the included study population of 291 patients, 251 (86.27 %) were male and 40 (13.73 %) were female. Out of all the co-morbidities, cardiovascular disease prevalence was highest with in DM group followed by TB-DM group. The prevalence of anaemia was found to be more in TB-DM group. Smoking and alcohol status was highest in TB group followed by TB-DM group.
Table 1.
Characteristics (demographic, clinical, biochemical, and nutritional) of study population.
| Sl. No. | Parameters | Group1 | Group2 | Group3 |
|---|---|---|---|---|
| Demographic parameters | ||||
| 1 | Age (Mean ± SD) | 51.92 ± 10.386 (n = 97) | 51.64 ± 11.69 (n = 97) | 51.96 ± 10.48 (n = 97) |
| 2 | Gender | |||
| Male (M) | 86.6 % | 86.6 % | 85.6 % | |
| Female (F) | 13.4 % | 13.4 % | 14.4 % | |
| M:F | 84:13 | 84:13 | 83:14 | |
| 3 | Family history | 1.03 % (n = 1) | 1.03 % (n = 1) | --- |
| 4 | Social habits | |||
| Alcohol | 2.06 % (n = 2) | 15.46 % (n = 15) | 10.31 % (n = 10) | |
| Smoking | 4.12 % (n = 4) | 11.34 % (n = 11) | 3.09 % (n = 3) | |
| Clinical parameters | ||||
| 5 | Comorbidities | |||
| Cardiovascular (%) | 26.80 % (n = 26) | 11.34 % (n = 11) | 68.04 % (n = 66) | |
| Renal (%) | 3.09 % (n = 3) | --- | 6.18 % (n = 6) | |
| Pulmonary (%) | 5.15 % (n = 5) | 9.27 % (n = 9) | 17.52 % (n = 17) | |
| Hepatic (%) | 3.09 % (n = 3) | 5.15 % (n = 5) | 4.12 % (n = 4) | |
| Anaemia (%) | 10.31 % (n = 10) | 9.27 % (n = 9) | 4.12 % (n = 4) | |
| RVD (%) | 1.03 % (n = 1) | 8.24 % (n = 8) | 4.12 % (n = 4) | |
| Thyroid disorder (%) | 3.09 % (n = 3) | 1.03 % (n = 1) | 6.18 % (n = 6) | |
| Biochemical parameters | ||||
| 6 | Glycemic Parameters | |||
| HbA1c (%) | 10.47 ± 2.25 (n = 95) | 5.66 ± 0.52 (n = 52) | 8.17 ± 2.35 (n = 93) | |
| FBS (mg/dL) | 194.33 ± 76.29 (n = 76) | 97 ± 16.11 (n = 17) | 175.07 ± 65.55 (n = 67) | |
| RBS (mg/dL) | 277.11 ± 114.54 (n = 67) | 113.31 ± 31.09 (n = 82) | 194.06 ± 82.92 (n = 65) | |
| PPBS (mg/dL) | 255.47 ± 114.48 (n = 40) | 140.33 ± 22.84 (n = 9) | 254.34 ± 77.35 (n = 53) | |
| 7 | Hematological parameters | |||
| Hb (g/dL) | 11.98 ± 2.14 (n = 97) | 11.2 ± 2.31 (n = 96) | 13.09 ± 2.39 (n = 97) | |
| WBC (µL) | 10.14 ± 3.06 (n = 96) | 10.71 ± 4.85 (n = 96) | 9.13 ± 4.04 (n = 97) | |
| Neutrophil (%) | 73.05 ± 8.82 (n = 94) | 75.42 ± 9.23 (n = 96) | 65.78 ± 12.53 (n = 96) | |
| ANC (%) | 7.44 ± 2.68 (n = 61) | 7.69 ± 3.87 (n = 68) | 5.84 ± 2.68 (n = 65) | |
| MCV (fL) | 80.27 ± 8.70 (n = 97) | 84.40 ± 8.84 (n = 96) | 84.66 ± 8.73 (n = 97) | |
| MCH (pg) | 26.47 ± 3.45 (n = 97) | 27.83 ± 3.33 (n = 96) | 28.46 ± 3.41 (n = 97) | |
| Ferritin(ng/mL) | 280.97 ± 262.67 (n = 10) | 487.62 ± 402.35 (n = 16) | 417.86 ± 311.81 (n = 14) | |
| Nutritional parameters | ||||
| 8 | Serum proteins | |||
| Albumin(g/dL) | 3.48 ± 0.54 (n = 91) | 3.11 ± 0.69 (n = 89) | 3.96 ± 0.53 (n = 93) | |
| Globulin(g/dL) | 3.58 ± 0.61 (n = 91) | 3.66 ± 0.74 (n = 88) | 3.07 ± 0.69 (n = 92) | |
| Total Proteins (g/dL) | 7.09 ± 0.69 (n = 87) | 6.78 ± 0.98 (n = 90) | 7.02 ± 0.79 (n = 93) | |
| 9 | Serum electrolytes | |||
| Potassium(mmol/L) | 4.46 ± 0.506 (n = 93) | 4.32 ± 0.58 (n = 92) | 4.34 ± 0.669 (n = 95) | |
| Magnesium(mg/dL) | 2.5 (n = 1) | 1.86 ± 2.88 (n = 7) | 2.02 ± 0.45 (n = 5) | |
| 10 | Serum vitamins | |||
| Vitamin D (ng/mL) | 16.0895 ± 12.638 (n = 19) | 23.56 ± 7.74 (n = 7) | 17.77 ± 8.28 (n = 10) | |
| Vitamin B12 (pg/mL) | 867.654 ± 560.75 (n = 13) | 577.12 ± 377.67 (n = 13) | 519.39 ± 398.85 (n = 16) | |
| Serum folate (µg/dL) | 11.5 ± 15.66 (n = 4) | 5.64 ± 4.06 (n = 7) | 4.57 ± 2.05 (n = 4) | |
RVD: retroviral disease, HbA1c: glycosylated hemoglobin, FBS: fasting blood sugar, RBS: random blood sugar, PPBS: post-prandial blood sugar, Hb: hemoglobin, WBC: white blood cells, ANC: absolute neutrophil count, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin.
Two out of 97 (2.06 %) patients had EPTB, and 2 patients (2.06 %) had XDR-TB in the TB group. A total of 11 out of 194 (5.6 %) patients from the TB-DM and TB group had previous history of TB/PTB and were readmitted in the hospital due to TB relapse. 143 out of 194 (73.7 %) patients from TB-DM and DM group had a history of DM.
The HbA1c was found to be in the range of poor diabetic control in TB-DM group (10.47 %) followed by DM group (8.17 %). FBS was found to be above normal range in TB-DM group followed by DM group as shown in Table 1. Statistical analysis was performed, taking TB-DM group as case, and comparing it with TB and DM groups as control. A mean difference of 4.80 and 2.29 was determined for TB and DM group, respectively, with p < 0.0001 compared with TB-DM group for HbA1c. ANOVA result for glycemic parameters is shown in Table 2 and Supplementary Figure 1 describes the graphical presentation of statistical results for glycemic parameters among all the study groups.
Table 2.
Comparison of glycemic, nutritional, and hematological parameters of TB-DM with TB and DM groups (ANOVA).
| Sl. No. | Parameters | Groups |
Mean difference | Standard error | Significance (p) | 95 % CI |
||
|---|---|---|---|---|---|---|---|---|
| Case (A) | Comparator (B) | Lower limit | Upper limit | |||||
| Glycemic parameters | ||||||||
| 1 | HbA1c (%) | TB-DM | TB | 4.80**** | 0.36 | <0.0001 | 3.93 | 5.67 |
| DM | 2.29**** | 0.29 | <0.0001 | 1.55 | 3.02 | |||
| 2 | FBS (mg/dL) | TB-DM | TB | 140.12**** | 12.25 | <0.0001 | 109.98 | 170.26 |
| DM | 36.19** | 12.25 | 0.014 | 6.05 | 66.33 | |||
| 3 | PPBS (mg/dL) | TB-DM | TB | 94.545**** | 17.17 | <0.0001 | 52.29 | 136.81 |
| DM | –32.85 | 17.22 | 0.164 | −75.22 | 9.52 | |||
| 4 | RBS (mg/dL) | TB-DM | TB | 96.17**** | 16.82 | <0.0001 | 54.78 | 137.55 |
| DM | 60.55*** | 16.86 | 0.002 | 19.06 | 102.05 | |||
| Nutritional parameters | ||||||||
| 5 | Albumin(g/dL) | TB-DM | TB | 0.42** | 0.15 | 0.017 | 0.06 | 0.77 |
| DM | −0.53*** | 0.15 | 0.001 | −0.89 | −0.17 | |||
| 6 | Globulin(g/dL) | TB-DM | TB | 0.03 | 0.16 | 0.977 | −0.36 | 0.42 |
| DM | 0.45** | 0.16 | 0.020 | 0.55 | 0.84 | |||
| 7 | Potassium(mmol/L) | TB-DM | TB | 0.18 | 0.15 | 0.468 | −0.18 | 0.54 |
| DM | 0.02 | 0.15 | 0.991 | −0.34 | 0.38 | |||
| 8 | Magnesium mg/dL) | TB-DM | TB | −0.11 | 0.06 | 0.192 | −0.25 | 0.04 |
| DM | −0.08 | 0.06 | 0.420 | −0.22 | 0.07 | |||
| 9 | Vitamin D (ng/mL) | TB-DM | TB | 1.45 | 1.01 | 0.357 | −1.03 | 3.94 |
| DM | 1.32 | 1.01 | 0.427 | −1.17 | 3.80 | |||
| 10 | Vitamin B12 (pg/mL) | TB-DM | TB | 58.55 | 43.77 | 0.410 | −49.17 | 166.28 |
| DM | 50.22 | 43.77 | 0.519 | −57.50 | 157.95 | |||
| 11 | Serum folate (µg/dL) | TB-DM | TB | 0.07 | 0.34 | 0.981 | −0.78 | 0.91 |
| DM | 0.29 | 0.34 | 0.707 | −0.56 | 1.13 | |||
| Hematological parameters | ||||||||
| 12 | Hb (g/dL) | TB-DM | TB | 0.90** | 0.34 | 0.032 | 0.06 | 1.74 |
| DM | −1.11*** | 0.34 | 0.006 | −1.95 | −0.27 | |||
| 13 | WBC (µL) | TB-DM | TB | −0.56 | 0.59 | 0.640 | −2.02 | 0.90 |
| DM | 0.91 | 0.59 | 0.313 | −0.55 | 2.37 | |||
| 14 | MCV (fL) | TB-DM | TB | −3.25 | 1.44 | 0.080 | −6.80 | 0.30 |
| DM | −4.38** | 1.44 | 0.011 | −7.93 | −0.84 | |||
| 15 | MCH (pg) | TB-DM | TB | −1.07 | 0.54 | 0.142 | −2.40 | 0.26 |
| DM | −1.99*** | 0.54 | 0.001 | −3.32 | −0.66 | |||
| 16 | ANC (%) | TB-DM | TB | −3.84 | 1.99 | 0.159 | −8.76 | 1.07 |
| DM | 5.70** | 1.99 | 0.018 | 0.78 | 10.62 | |||
| 17 | Ferritin (ng/mL) | TB-DM | TB | −51.47 | 27.14 | 0.168 | −118.25 | 15.32 |
| DM | −31.34 | 27.14 | 0.514 | −98.13 | 35.44 | |||
HbA1c: glycosylated hemoglobin, FBS: fasting blood sugar, RBS: random blood sugar, PPBS: post-prandial blood sugar, TB-DM: tuberculosis-diabetes mellitus, TB: tuberculosis, DM: diabetes mellitus, Hb: hemoglobin, WBC: white blood cells, ANC: absolute neutrophil count, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, CI: confidence interval; ****(p < 0.0001), ***(p < 0.001), **(p < 0.01).
3.2. Nutritional parameters
There was no significant difference among the groups for nutritional parameters such as albumin, globulin, and total proteins. However, vitamin B12 was highest in TB-DM group (867.65 ± 560.75 pg/ml). The statistical analysis describes insignificant outcomes for vitamin D and vitamin B12. Mean ± SD and statistical analysis results are shown in Table 1 and Table 2, respectively. The graphical presentation is depicted in Supplementary Figure 2.
3.3. Hematological parameters
The mean value for Hb was highest in DM group (13.09 g/dl), as shown in Table 1. Statistical significance was found for Hb, MCV, MCH, and neutrophil, as shown in Table 2. Furthermore, the significance(p) for ferritin in TB and DM group was calculated as 0.168 and 0.514, respectively. Supplementary Figure 3 represents graphical presentation of statistical association for hematological parameters.
3.4. Adverse reactions
ATT-induced adverse drug reactions were the most common among the study population, especially in the TB-DM and TB groups. 4 out of 194 records presented ADRs including ATT-induced rash, hepatitis, pyrazinamide-induced hyperuricemia, and rifampicin-induced interstitial nephritis.
Based on our study findings, 95.83 % patients had HbA1c > 6.5 in the TB-DM group. Similarly, a high percentage of FBS and RBS level were found in TB-DM group. Considering the nutritional parameters, a large percentage of low level of serum albumin patients was found in TB group (71.91 %). High percentage of vitamin D deficiency was found in TB-DM group (73.68 %) followed by in DM (50 %) and TB group (42.86 %). 66.67 % of patients were found to have higher concentration of vitamin B12 (>2000 pg/ml) in TB-DM group. The comparative data of all the parameters is depicted in Table 3.
Table 3.
Comparation of subcategories of various parameters among the study groups.
| Sl. No. | Parameters | Inference | TB-DM |
TB |
DM |
|||
|---|---|---|---|---|---|---|---|---|
| n | % | n | % | n | % | |||
| 1 | HbA1c | Normal | 0 | 0 | 22 | 42.31 | 4 | 4.301 |
| Prediabetes | 3 | 3.13 | 28 | 53.85 | 16 | 17.204 | ||
| DM | 92 | 95.83 | 2 | 3.84 | 73 | 78.49 | ||
| 2 | FBS | Normal | 4 | 5.19 | 9 | 52.94 | 3 | 4.47 |
| Impaired glucose tolerance | 12 | 15.58 | 8 | 47.06 | 12 | 17.91 | ||
| DM | 61 | 79.22 | 0 | 0 | 52 | 77.61 | ||
| 3 | RBS | Normal | 5 | 7.46 | 68 | 82.93 | 18 | 27.69 |
| Impaired glucose tolerance | 13 | 19.403 | 12 | 14.63 | 21 | 32.31 | ||
| DM | 49 | 73.13 | 1 | 1.22 | 25 | 38.46 | ||
| 4 | PPBS | Normal | 4 | 10 | 4 | 44.44 | 3 | 5.66 |
| Impaired glucose tolerance | 8 | 20 | 5 | 55.55 | 9 | 16.98 | ||
| DM | 26 | 65 | 0 | 0 | 41 | 77.36 | ||
| 5 | Hb | Normal | 27 | 27.84 | 12 | 12.37 | 49 | 50.52 |
| Low | 68 | 70.10 | 83 | 85.57 | 44 | 45.36 | ||
| High | 2 | 2.06 | 2 | 2.06 | 4 | 4.12 | ||
| 6 | WBC | Normal | 51 | 53.13 | 49 | 50.52 | 68 | 70.1 |
| Low | 0 | 0 | 5 | 5.15 | 2 | 2.06 | ||
| High | 45 | 46.87 | 43 | 44.33 | 27 | 27.84 | ||
| 7 | MCV | Normal | 33 | 34.02 | 45 | 46.39 | 59 | 60.82 |
| Low | 62 | 63.92 | 48 | 49.48 | 35 | 36.08 | ||
| High | 2 | 2.06 | 4 | 4.12 | 3 | 3.09 | ||
| 8 | MCH | Normal | 38 | 39.18 | 46 | 47.42 | 62 | 63.92 |
| Low | 55 | 56.7 | 42 | 43.29 | 26 | 26.8 | ||
| High | 4 | 4.12 | 9 | 9.28 | 9 | 9.28 | ||
| 9 | Neutrophil | Normal | 51 | 54.26 | 36 | 37.5 | 64 | 66.67 |
| Low | 0 | 0 | 0 | 0 | 5 | 5.21 | ||
| High | 43 | 45.74 | 60 | 62.5 | 27 | 28.12 | ||
| 10 | Ferritin | Normal | 5 | 45.45 | 6 | 37.5 | 3 | 20 |
| Low | 1 | 9.09 | 1 | 6.25 | 3 | 20 | ||
| High | 0 | 0 | 9 | 56.25 | 9 | 60 | ||
| 11 | Total Proteins | Normal | 78 | 88.64 | 68 | 75.56 | 77 | 82.8 |
| Low | 2 | 2.27 | 14 | 15.56 | 5 | 5.38 | ||
| High | 7 | 7.95 | 8 | 8.89 | 11 | 11.83 | ||
| 12 | Potassium | Normal | 83 | 89.25 | 79 | 85.87 | 73 | 76.04 |
| Low | 4 | 4.3 | 6 | 6.52 | 9 | 9.38 | ||
| High | 6 | 6.45 | 7 | 7.61 | 14 | 14.58 | ||
| 13 | Albumin | Normal | 48 | 52.75 | 26 | 29.21 | 74 | 79.57 |
| Low | 43 | 47.25 | 64 | 71.91 | 18 | 19.35 | ||
| High | 0 | 0 | 0 | 0 | 1 | 1.08 | ||
| 14 | Globulin | Normal | 52 | 57.14 | 41 | 46.59 | 73 | 79.35 |
| Low | 0 | 0 | 1 | 1.14 | 2 | 2.17 | ||
| High | 39 | 42.86 | 46 | 52.27 | 17 | 18.48 | ||
| 15 | Vitamin D | Normal | 2 | 10.53 | 1 | 14.29 | 1 | 10 |
| Insufficient | 3 | 15.79 | 3 | 42.86 | 4 | 40 | ||
| Deficient | 14 | 73.68 | 3 | 42.86 | 5 | 50 | ||
| 16 | Vitamin B12 | Normal | 5 | 33.33 | 5 | 25 | 7 | 36.84 |
| Insufficient | 0 | 0 | 0 | 0 | 2 | 10.53 | ||
| Deficient | 0 | 0 | 1 | 5 | 2 | 10.53 | ||
| High | 10 | 66.67 | 13 | 65 | 8 | 42.11 | ||
HbA1c: glycosylated hemoglobin, FBS: fasting blood sugar, RBS: random blood sugar, PPBS: post-prandial blood sugar, TB-DM: tuberculosis-diabetes mellitus, TB: tuberculosis, DM: diabetes mellitus, Hb: hemoglobin, WBC: white blood cells, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin.
4. Discussion
The bidirectional relationship between malnutrition and conditions such as TB and DM has been known for a long back. With the increasing prevalence of TB in the diabetic population, malnutrition becomes a major link in worsening the conditions. DM increases the risk of active TB from latent TB infection (LTBI). TB-DM co-morbidity has surpassed percent of TB-HIV co-infection [16]. The incidence of co-morbidity remains high in countries with high HIV rates, malnutrition or poor nutritional conditions, and inadequate TB control infrastructure [17].
We have observed a high HbA1c value in the TB-DM group as compared to the DM group. The findings were similar in the case of the RBS and FBS level. The findings suggest a positive role of TB infection-causing poor glycemic control in diabetes. A statistical significance of p < 0.001 was found for HbA1c, RBS, FBS, and PPBS in the TB-DM group compared to the TB and DM group. Previous studies suggest that TB may cause impaired glucose intolerance and hyperglycemia [18], [19]. Furthermore, ATT drugs such as isoniazid and rifampicin interact with oral hypoglycemic agents causing poor glycemic control [19]. A study in Tanzania determined impaired glucose tolerance in TB-DM population with p < 0.001 [20]. A study in a similar setting as the present study determined a 25.3 % prevalence of DM among TB patients, out of which 90.8 % patients had elevated HbA1c. 5 % study population in TB-DM group and 25 % in TB group were underweight (BMI < 18.4) [21].
According to the ‘The State of Food Security and Nutrition in World, 2020′ report, India’s 14 % (189.2 million) population is undernourished [22], despite being one of the world’s largest producers of milk, rice, wheat, pulses, and vegetables [23]. Malnutrition in developing countries like India often leads to low birth weight, presence of developmental decay, and increased diarrhea episodes [24]. Based on our study findings, 47.25 % of patients had low level of serum albumin in TB-DM group; however, TB group had high percentage of low albumin (71.91 %). Considering vitamin D level, 73.68 % in TB-DM group had vitamin D deficiency (VDD) compared to 42.86 % and 50 % in TB and DM group, respectively. Zhao et al. performed a study on vitamin D status of TB-DM patients and determined 84 % of the study population had VDD, of which 51 % had VDD, and 33 % had severe VDD [25]. A study performed by Lin et al. associated VDD with unfavorable treatment outcomes in TB patients found that 74.2 % of the study population was vitamin D deficient, and 40.8 % of patients had unfavorable treatment outcomes suggesting intensive support to patients and early detection of DM [26]. Individualized dietary intervention in TB-DM patients improved nutritional status and lower sputum positive cases compared to the control group with a self-controlled diet [27]. Vitamin A supplementation along with other micronutrients has been found to decrease morbidity, mortality, and sputum smear conversion time in TB patients [28].
TB-DM co-morbidity leads to worsening of health conditions. A higher proportion of patients with low levels of Hb, MCV, and MCH were found in TB-DM group compared to the other groups. The findings of our study suggest an increased risk of iron deficiency anemia, microcytic and macrocytic anemia in this group. Moreover, dietary practices and nutritional supplementation have been shown to improve nutritional status in TB patients [29].
5. Conclusion
Based on the findings of our study, the TB-DM group was significantly associated with elevated glycemic parameters than TB and DM groups. Nutritional deficiencies such as vitamin D and low serum level of albumin were found in the TB-DM group, however not statistically significant. A higher prevalence of low levels of MCV and MCH were found in the TB-DM group, suggesting an increased risk of anemia. We suggest an early detection of nutritional deficiencies and dietary interventions (micro- and macro-nutrient supplementation) along with ATT in patients with TB-DM co-morbidity to reduce morbidity and mortality rate, as well as reducing sputum smear conversion time and relapse or recurrence rate.
6. Author’s contributions
SSM contributed for the concept, design of manuscript. SSM and KS contributed for the intellectual inputs. DP contributed for data collection and data analysis. DP, TB and SJK contributed for manuscript writing. DP, TB, SJK, PM, SSM, and KS critically evaluated the manuscript. All authors contributed to the article and approved the submitted version.
Funding
This research work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
CRediT authorship contribution statement
Divya Girishbhai Patel: Writing – review & editing, Writing – original draft, Formal analysis, Data curation, Conceptualization. Tejaswini Baral: . Shilia Jacob Kurian: Writing – original draft. Pravachana Malakapogu: Writing – review & editing, Writing – original draft. Kavitha Saravu: Writing – review & editing, Conceptualization. Sonal Sekhar Miraj: Writing – review & editing, Supervision, Methodology, Data curation, Conceptualization.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The authors gratefully acknowledge the help and facilities provided by Manipal College of Pharmaceutical Sciences; Kasturba Hospital, Manipal; Manipal Center for Infectious Diseases, Prasanna School of Public Health; and Manipal Academy of Higher Education, Manipal, India.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jctube.2024.100428.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
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