|Year : 2018 | Volume
| Issue : 2 | Page : 222-226
Lung diffusion capacity disorder in indonesian patients with Type 2 diabetes mellitus and the related factors
Haruyuki Dewi Faisal1, Budhi Antariksa1, Ratnawati1, Rochsismandoko2, Faisal Yunus1, Fariz Nurwidya1
1 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia, Persahabatan Hospital, Jakarta, Indonesia
2 Division of Endocrinology, Metabolic Diseases and Diabetes, Department of Internal Medicine, Persahabatan Hospital, Jakarta, Indonesia
|Date of Web Publication||20-Jun-2018|
Jalan Persahabatan Raya No. 1, Rawamangun, Jakarta 13230
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Type 2 diabetes mellitus (T2DM) is a disorder characterized by chronic hyperglycemia and causing both macro- and micro-vascular complications. Lung as a microvascular-contained organ may be affected by the T2DM microvascular complication that results in lung diffusion capacity disorder. Methods: This cross-sectional study involved adult T2DM patients, without overt lung disorder, terminal kidney failure, or cardiovascular disorder, and who were on an outpatient basis. Patients who were recruited through consecutive sampling underwent interview session, physical examination, laboratory test, spirometry, and diffusing capacity of the lungs for carbon monoxide (DLCO) test. Results: Decreasing DLCO value has a significant relation to the high level of glycated hemoglobin (HbA1c) (P < 0.05). Patients with HbA1c >6.5 have 21 times risk to have decreasing DLCO value compared to patients with HbA1c <6.5 (P < 0.05). Conclusion: Uncontrolled glycemic status significantly contributed in the decreasing lung diffusion capacity among patients with T2DM. This study implies the importance of controlling blood glucose as a measure to preserve the lung diffusion capacity.
Keywords: Glycated hemoglobin, lung capacity, type 2 diabetes mellitus
|How to cite this article:|
Faisal HD, Antariksa B, Ratnawati, Rochsismandoko, Yunus F, Nurwidya F. Lung diffusion capacity disorder in indonesian patients with Type 2 diabetes mellitus and the related factors. J Nat Sc Biol Med 2018;9:222-6
|How to cite this URL:|
Faisal HD, Antariksa B, Ratnawati, Rochsismandoko, Yunus F, Nurwidya F. Lung diffusion capacity disorder in indonesian patients with Type 2 diabetes mellitus and the related factors. J Nat Sc Biol Med [serial online] 2018 [cited 2019 Nov 12];9:222-6. Available from: http://www.jnsbm.org/text.asp?2018/9/2/222/234700
| Introduction|| |
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by an increase in blood glucose related to insulin resistance or deficiency. The prevalence of patients with T2DM in 2014 was estimated at 9% of the population aged over 18 years. It is estimated that there will be 180 million patients with T2DM by 2030 globally. Mortality due to diabetes in 2012 was 1.5 million worldwide.,
T2DM can cause microvascular complications due to the process of glycosylation of blood vessels and tissue. Factors influencing T2DM complications include age, sex, obesity, duration of disease, and uncontrolled glycemic control., The anatomy of the lung consists of a dense capillary network that is prone to the diabetic-related microvascular complications. Clinical detection of decreased pulmonary diffusing capacity in patients with T2DM is difficult even though there has been an interruption in the microvascular level of the lung.
Accumulating evidence suggests that there is a relationship between impaired lung diffusion capacity with T2DM, because of a decrease in lung function contributed to the morbidity and mortality among T2DM patients. However, there has been no study that elucidates the value of diffusion capacity of the lungs in Indonesian patients with T2DM.,
| Methods|| |
This study is a cross-sectional study in T2DM patients who attend the Outpatient Clinic of Internal Medicine at the Persahabatan Hospital, Jakarta, during September–October 2016. The present study has been granted ethical approval by the Ethics Committee of the Faculty of Medicine University of Indonesia (No. 515/UN2.F1/ETIK/2016). Inclusion criteria were ambulatory patients who are diagnosed as T2DM, age over 18 years, and willing to sign an informed consent form after explanations. Exclusion criteria were pregnant or breastfeeding women, patients with severe pulmonary disorders (chronic obstructive pulmonary disease [COPD], pulmonary tuberculosis [TB], and asthma), terminal renal failure, and/or are in hemodialysis, with chronic heart failure, and unable to complete the procedures of spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Patients who met the inclusion criteria were recruited by consecutive sampling. After an interview, laboratory examination, and chest X-ray procedure, the patients underwent spirometry and DLCO tests. Spirometry test was performed by SPIROBANK II (Medical International Research, Rome, Italy) and DLCO examination was done using the Easyone™ Prolab (NDD Med, Andover, MA, USA). The technique used was a single breath method. First, patients were asked to breathe normally. After a regular breathing pattern, the patients were asked to perform maximal expiration. After that, the patients were instructed to do maximal inspiration. Gas valve was opened so that the gas can get into the lungs. Furthermore, patients were instructed to hold their breath for 10 s. Finally, the patients were doing the maximum exhalation without hesitating. Inspection was carried out at least 2 times. The time between the examinations was at least 4 min. Acceptable results were obtained from the two test results with the value of the difference of 2 ml/min/mmHg.
The obtained data were subsequently analyzed using the Statistical Package for the Social Sciences (SPSS) software program version 21 (IBM Corp, Armonk, NY, USA). Data distribution normality was determined by Kolmogorov–Smirnov analysis. Odds ratio (OR) was calculated using Chi-square or Fisher's exact test. Unless stated otherwise, data were presented as mean ± standard deviations. P < 0.05 was considered statistically significant.
| Results|| |
There were 114 patients who met the inclusion criteria but 79 patients were excluded because four patients had pulmonary TB, 18 patients had asthma, 9 patients had COPD, 7 patients had renal failure, 15 patients had chronic heart failure disease, and 4 patients failed in performing the maneuver. Demographic details of the 35 enrolled patients, including age, gender, body mass index (BMI), duration of having T2DM, and others are summarized in [Table 1].
First, we investigated the lung volume and determined the DLCO values. Average forced vital capacity (FVC) value of the entire patient population of this study was 2009.43 ± 667.57 ml. Less than half of the patients showed restricted lung with a percentage of FVC/prediction below 80%. The majority of the studied patients (91.4%) had no obstruction in their airway with a percentage of forced expiratory volume in 1 s/FVC 75% or more. Nearly half of the patients displayed a decrease in the DLCO values and most of these patients had mild degree followed by moderate degree. However, there were no patients with a severe reduction in DLCO in this study. The details of lung volume findings are summarized in [Table 2].
|Table 2: Distribution of lung volume and diffusing capacity of the lungs for carbon monoxide value|
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We then examined the influencing factors and the association with the DLCO values. Variables such as age, gender, BMI, duration of T2DM, and the level of urinary albumin did not have a significant association with DLCO. However, there was a statistically significant association between high levels of glycated hemoglobin (HbA1c) with a decrease in DLCO value (P = 0.006) as summarized in [Table 3].
|Table 3: The relationship between the characteristics and diffusing capacity of the lungs for carbon monoxide value|
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Next, we analyzed the correlation between spirometry and DLCO results. From [Table 4], we found that there were 9 of 15 patients (56.2%) patients with restriction by spirometry and decrease in DLCO values, but this was not significant statistically. Patients with obstruction by spirometry have an OR of 1.54 of having a decrease in lung diffusion capacity by DLCO; however, this was not statistically significant (P > 0.05).
|Table 4: Correlation between spirometry and diffusing capacity of the lungs for carbon monoxide values|
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Finally, we seek the factors that affect the decrease in DLCO value. In the bivariate analysis, there were four variables affecting the decrease in DLCU value, i.e., urinary albumin, HbA1c, gender, and percentage of FVC to prediction. Four of these variables then underwent multivariate analysis by logistic regression. In the multivariate analysis as described in [Table 5], we found that only HbA1c significantly affected the decrease in DLCO value in our T2DM patients (P< 0.05). Patients with HbA1c levels above 6.5 had a 21.73 times risk of a decrease in lung diffusion capacity compared to those with HbA1c <6.5.
|Table 5: Multivariate analysis of factors affecting the decreased diffusion capacity of the lungs for carbon monoxide value|
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| Discussion|| |
Initially, 114 patients fulfilled the inclusion criteria; however, a substantial number of patients were then excluded. The main reason for being excluded was pulmonary TB. Persahabatan Hospital, where this study was conducted, is a national reference hospital for respiratory disease in Indonesia with very high prevalence of TB in tropical region. Comorbidities (i.e., pulmonary TB, asthma, COPD, renal failure, and chronic heart failure) could affect lung diffusion capacity through mechanisms such as inflammation and interstitial edema. Despite their potential role in causing restrictive lung disorder, these comorbidities are confounding factors that should be excluded in our effort to clarify the association between T2DM and impaired pulmonary diffusion capacity.
Patients with T2DM in this study had similar mean age, gender distribution, and BMI distribution with the study by Malik et al. who found a mean age of T2DM to be 56.9 ± 7.3 years. Another study in Turkey by Guvener et al. also had a similar mean age of 56.3 ± 9.7 years with slightly female predominance and higher BMI. Anandhalakshmi et al. also had a similar mean BMI of 26.06 ± 4.03 kg/m 2. The mean hemoglobin values in this study were consistent with the results obtained in studies by Guvener et al. who had a mean value of 13.8 ± 1.2 g/dL. Another study by Fuso et al. showed quite similar mean value of 13.49 ± 1.28 g/dL.
Duration of T2DM in this study was higher than the study by Guvener et al. and Saler et al., with the mean duration of T2DM to be 5.8 ± 7.8 years and 7.6 ± 5.5 years, respectively. This difference may be because of different lifestyles in the country. However, another study in Greece by Boulbou et al. had a higher average of 16.6 ± 8.8 years.
Most of the patients in this study had a HbA1c level above 6.5 that is consistent with the previous study by Malik et al. who found that more than half had HbA1c >6.5. The mean HbA1c in this study was similar to the study by Sinha et al., with mean HbA1c of 8.6% ± 1.4%. Another study by Agarwal et al. also had a similar mean of 8.54% ± 1.29%. However, other researchers obtained a lower mean value as in the study by Guvener et al., 7.4% ± 5.4%; Saler et al., 7.5% ± 1.8%; and Uz-zaman et al., 7.07% ± 1.492%. Taken together, there is a tendency that T2DM patients in developed countries have a better glycemic control level.
In terms of lung restriction, the average of FVC value in this study was lower than the study conducted in Pakistan by Niazi et al., with a mean FVC value of 2500 ± 700 ml. A study by Malik et al. showed a significant relationship between poor glucose control and a decreased FVC percentage in the diabetic group. The possible mechanisms might be because of the glycosylation of connective tissue that resulted in decreased lung recoil.
The average values of DLCO in this study were lower than that were obtained by Saler et al., 17.53 ± 3.52 ml/min/mmHg versus 23.3 ± 6.8 ml/min/mmHg, respectively. Our percentage of DLCO predictive value was also lower, 76% versus 93.6%. Variables that may be associated with the DLCO values include age, gender, duration of T2DM, BMI, microalbuminuria, and HbA1c. However, we only found a significant relationship between increasing HbA1c levels with a decrease in DLCO-predicted values (P = 0.006). This is consistent with a study by Anandhalakshmi et al. who revealed a significant relationship between poor glycemic control (cutoff point HbA1c 7%) with a decrease in DLCO-predicted values. Uz-Zaman et al. also found negative correlation between DLCO-predicted values with the increased levels of HbA1c (r = −0.65; P < 0.05). Agarwal et al. also had the same results with decrease in DLCO-predicted values along with the increased levels of HbA1c. These findings strengthen the biological concept of glycosylation in poor glycemic control which causes thickening of the basement membrane as well as pulmonary capillary basement membrane, and eventually interferes the gas diffusion within the lung. Accumulating evidence suggests that glycosylation of pulmonary elastin fibers and collagen results in inappropriate cross-linking, reduced degradation, and emphysema-like decrements in alveolar surface area that will cause stiffening of the lungs, impaired vascular diffusion, and reduced elastic recoil.
Multivariate analysis using binary logistic regression method to four variables, i.e., urine albumin, HbA1c, gender, and FVC value, confirmed only HbA1c level to be statistically significant. The level of HbA1c >6.5 had a decrease in DLCO risk by 21 times. Several other studies have also noted the implication of increased HbA1c level in the decrease in DLCO values. As we have mentioned before, Anandhalaksmhi et al. and Uz-zaman et al. showed results that are in accordance with our findings. Study by Sinha et al. revealed a significant correlation (r = −0.62; P < 0.05) between HbA1c levels and a decrease in DLCO in a group of T2DM patients with microvascular complications. These results point to a regulation of thickening of the capillary basement membrane of patients with T2DM. In a study involving autopsied material, Weynand et al. found that endothelial capillary basal lamina and alveolar epithelia were significantly thicker in samples from diabetics than in non-diabetics subjects. High levels of HbA1c that represent uncontrolled glycemic status lead to microvascular complications including impaired pulmonary diffusion capacity.
Classically, controlled glycemic status is intended to prevent from vascular-related target organ complications such as cerebrovascular disease, coronary artery disease, and chronic kidney disease. The current data convey an important message that lung function is at serious risk under uncontrolled glycemic status. Our findings emphasize the need for incorporation of lung function preservation, as well as other target organ protection, as the goal in treating patients with T2DM.
The present study was a study with cross-sectional design; therefore by the nature of its study design, it only obtained result at a specific point in time. Another limitation of this study was that limited sample size which involved 35 enrolled patients with T2DM. Further study involving larger sample size might reveal more factors that contribute to the decreasing pulmonary diffusion capacity among T2DM patients.
| Conclusion|| |
Nearly half of the T2DM patients displayed a mild-to-moderate decrease in the DLCO values. To the best of our knowledge, our study is the first to reveal a statistically significant association between HbA1c levels with a decrease in DLCO value among Indonesian patients with T2DM. Although it did not reach a statistically significant threshold, we also found that obstruction by spirometry has a correlation with a decrease in lung diffusion capacity. Among the investigated variables, uncontrolled glucose control significantly increased the risk of reduced lung diffusion capacity among T2DM patients.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]