Diabetic neuropathy, a cause of pulmonary dysfunction in patients of type 2 diabetes mellitus: A prospective cross-sectional study

Piyush Gautam; Ahmad Faraz; Hamid Ashraf; Sangeeta Singhal

doi:10.4103/bjem.bjem_15_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 2 | Issue : 1 | Page : 35-40

Diabetic neuropathy, a cause of pulmonary dysfunction in patients of type 2 diabetes mellitus: A prospective cross-sectional study

Piyush Gautam¹, Ahmad Faraz¹, Hamid Ashraf², Sangeeta Singhal¹
¹ Department of Physiology, J.N Medical College, Aligarh Muslim University, Aligarh, India
² Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N Medical College, Aligarh Muslim University, ALigarh, India

Date of Submission	07-Nov-2022
Date of Acceptance	10-Dec-2022
Date of Web Publication	23-Jan-2023

Correspondence Address:
Hamid Ashraf
Jawaharlal Nehru Medical College Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_15_22

Abstract

Introduction: Diabetic neuropathy (DN) is most commonly associated with diabetic peripheral neuropathy (DPN). About 66% of diabetic patients have either clinical or subclinical neuropathy. Materials and Methods: One hundred and twenty patients were enrolled in our study, 60 patients are of Type 2 diabetes mellitus (T2DM) with neuropathy (DPN), and 60 were of T2DM without neuropathy. They were assessed for neuropathy. Serum fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin A1C (HbA1_C), and duration of disease were obtained from the patients. Forced expiratory volume at the 1^st s (FEV₁) and forced vital capacity were recorded and % FEV₁ was calculated. Results: The mean age of T2DM with neuropathy was 49.17 ± 7.1 and in patients of T2DM without neuropathy was 46.63 ± 8.028. The mean value of % FEV₁ in T2DM with neuropathy is 95.45 ± 7.16, while in T2DM without neuropathy, it is 83.53 ± 6.22, and the difference was statistically significant. Linear correlation of % FEV₁ with fasting plasma glucose (FPG) (r = 0.474, P = 0.008) and HbA1_C (r = 0.588, P = 0.001) shows a statistically significant association in diabetic peripheral neuropathy. The standardized β weights of FPG, postprandial plasma glucose, and HbA1_C show significant values in patients of DPN. Conclusion: Diabetic peripheral neuropathy (DPN) is associated with decreased pulmonary function as compared to patients of diabetes without neuropathy, the glycemic status of patients may also adversely affect % FEV₁. Thus, proper control of hyperglycemia will decrease the further progression of the disease. We also suggest performing pulmonary function test in patients of diabetes mellitus with DN in the preoperative period so as to optimize the perioperative care.

Keywords: Lung dysfunction, pulmonary function test, Type 2 diabetes mellitus

How to cite this article:
Gautam P, Faraz A, Ashraf H, Singhal S. Diabetic neuropathy, a cause of pulmonary dysfunction in patients of type 2 diabetes mellitus: A prospective cross-sectional study. Bangladesh J Endocrinol Metab 2023;2:35-40

How to cite this URL:
Gautam P, Faraz A, Ashraf H, Singhal S. Diabetic neuropathy, a cause of pulmonary dysfunction in patients of type 2 diabetes mellitus: A prospective cross-sectional study. Bangladesh J Endocrinol Metab [serial online] 2023 [cited 2023 Mar 29];2:35-40. Available from: https://www.bjem.org/text.asp?2023/2/1/35/368415

Introduction

Diabetes mellitus (DM) is a miscellaneous group of a multifactorial polygenic syndrome, which has become one of the leading causes of morbidity and mortality across the world. According to the International Diabetes Federation, 425 million had diabetes in 2016, and by the year 2045, the number will rise to 645 million.^[1] This prevalence has risen at an alarming pace in developing countries. According to the research conducted by the Indian Council of Medical Research (ICMR)-Indian Diabetes, there are 62.4 million reported people with Type 2 DM, and around 77 million people lie in a prediabetic zone in India.^[2]

One of the most common complications associated with DM is diabetic neuropathy (DN). The American Diabetes Association recognized it as “the presence of symptoms and/or signs of peripheral nerve dysfunctions in people with diabetes after exclusion of other causes.”^[3] The risk of developing DN is proportional to the magnitude and duration of hyperglycemia like other microvascular complications, but some individuals may possess genetic attributes for DN. According to an estimate 66% of diabetic patients have clinical or subclinical neuropathy.^[4] The most common type of DN is distal sensory-motor polyneuropathy. It accounts for about 75% of all cases DN, and thus is the focus of our study.^[5]

Pulmonary function test is the basic and most widely used test to analyze the lung volumes and flow, which is ideal for describing the effects of obstructions or restrictions on lung functions. DM, being a systemic disease, also affects the lungs causing the restrictive type of ventilatory changes. The etiopathogenesis of pulmonary dysfunction in patients of DM is complex multifactorial and poorly understood. The proposed mechanisms for pulmonary abnormalities in people with DM comprise raised blood glucose and insulin level,^[6],[7] autonomic dysfunction,^[8] increased oxidative stress,^[9] angiopathy of pulmonary and alveolar vessels,^[10],[11] abnormal glycosylation of proteins,^[12],[13] changes in connective tissue,^[14],[15] abnormalities of surfactant,^[16],[17] and respiratory muscles.^[18],[19] DM causes a reduction in elastic recoil, reduced lung volume, diminished respiratory muscle performance, chronic low-grade inflammatory changes in lungs,^[20],[21] and autonomic neuropathy involving respiratory muscles.^[22] During the perioperative period, patients with diabetes had significantly lengthier ventilation time and increased frequency of reintubation.^[23] Although the underlying mechanism which relates Type 2 diabetes to reduce lung functions still remains unclear. Despite the unclear nature, the relationship between DM and pulmonary function tests (PFTs) remains important because of potential epidemiological and clinical implications as there is limited evidence in literature. Hence, we have conducted this study which aims to explore the abnormalities in PFT in a patient of Type 2 DM (T2DM) with and without DN. Our study's objective is to study the effect of DN on lung function and correlate various parameters of glycemic control with parameters of PFT.

Materials and Methods

After approval of the study from the Institutional Ethical Committee, patients attending the endocrinology outpatient department were evaluated for inclusion and exclusion criteria. Patients who gave valid written and informed consent were included in the study.

One hundred and twenty patients with diabetes were assessed for the inclusion criteria, and exclusion criteria, and 60 patients with diabetes were included in the study, which met the inclusion and exclusion criteria and gave valid written consent. Those patients who had bronchial asthma, chronic obstructive pulmonary disease, any other respiratory disease, hypothyroidism, hypertension, renal failure, liver failure, patients taking steroids, and neuropathies other than DN were excluded from the study.

Clinical evaluation

One hundred and twenty patients were enrolled in our study; 60 patients are of T2DM with neuropathy (DPN), and 60 were of T2DM without neuropathy. They were assessed for neuropathy by evaluating ankle reflex, pinprick, vibration sense, and monofilament testing. The latest values of fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin (HbA1_C), and duration of disease were obtained from the patients. Body mass index (BMI) was calculated from height in meters and weight in kilograms which was measured as per the standard procedure.

Sampling procedure

The diagnosis of diabetes was established as per the criteria of the American Diabetes Association: fasting plasma glucose (FPG) ≥126 mg/dL, 2-h plasma glucose ≥200 mg/dL, during an oral glucose tolerance test, HbA1_C ≥6.5% (48 mmol/L), or in a patient with classic symptoms of hyperglycemia random plasma glucose ≥200 mg/dl.^[24] These samples were taken when the patient presented in our outpatient department.

Diagnosis of neuropathy

The following clinical tests were used to assess neuropathy

Small-fiber function: pinprick and temperature sensation
Large-fiber function: vibration perception, proprioception, 10-g monofilament, and ankle reflexes. A 128-Hz tuning fork was used to assess vibration perception.

Assessment of light-touch perception using a 10-g monofilament should include an evaluation of the dorsal aspect of the great toe bilaterally as previously validated by Perkins et al.^[25]

Spirometry

Pulmonary function is recorded using a “Spirodoc spirometer.” The software was employed for the computer-aided spirometry. The subjects demonstrated the maneuvers and allowed rehearsal. After enough practice, subjects performed spirometry to record. For recording forced vital capacity (FVC), the subjects were instructed to take a deep and maximum inspiration and breathe out as forcefully and as fast as and as complete as possible. Graphic records and values of FVC and its components were obtained.

Statistical analysis

Statistical analysis of the data was performed using the 21^st edition of the Software Statistical Package for the Social Sciences (SPSS) for Windows (IBM Corp. Armonk, NY, USA). The continuous variable was expressed as mean ± standard deviation. Means were compared by unpaired t-test; the association between continuous variables was tested by linear correlation using Pearson's coefficient. Multivariate linear regression analyses were also done. P < 0.05 was considered statistically significant.

Results and Observation

Baseline characteristics of study population

In 60 patients of T2DM with neuropathy, 22 were male and 38 were female, while in patients of T2DM without neuropathy, 26 were male and 34 were female. The mean age of T2DM with neuropathy was 49.17 ± 7.1 and in patients of T2DM without neuropathy was 46.63 ± 8.028; it was statistically nonsignificant. Patients of T2DM with DN have a significantly longer disease duration compared with those without DN. There was no significant difference in BMI between the two groups. There were significantly elevated levels of FPG, postprandial glucose, and HbA1c value in T2DM patients with DN [Table 1].

Table 1: Baseline characteristics of Type 2 diabetic patients with and without neuropathy

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Pulmonary function test in patients of diabetes mellitus with and without diabetic neuropathy

The mean value of forced expiratory volume at the 1^st s (FEV₁) in T2DM with neuropathy is 1.75 ± 0.48, while in T2DM without neuropathy, it is 2.32 ± 0.54; the comparison of FEV₁ in both the groups shows the statistically significant result. The mean value of FVC in T2DM with neuropathy is 1.83 ± 0.46, while in T2DM without neuropathy, it is 2.47 ± 0.59, and the difference was statistically significant. The mean value of % FEV₁ in T2DM with neuropathy is 95.45 ± 7.16, while in T2DM without neuropathy, it is 83.53 ± 6.22, and the difference was statistically significant. There was no significant difference in the peak expiratory flow rate (PEFR) and forced expiratory flow (FEF) 25%–75% between both the groups [Table 2].

Table 2: Pulmonary function parameters in cases and controls of Type 2 diabetic subjects

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Correlation of glycemic parameters and pulmonary function test

Linear correlation of % FEV₁ with FPG (r = 0.474, P = 0.008) shows a statistically significant association in DPN while all other parameters show a negative association. FEV₁, FVC, % FEV₁, PEFR, and FEF 25%–75% show no statistically significant association with postprandial plasma glucose (PPG). The % FEV₁ (r = 0.588, P = 0.001) shows a statistically significant association with HbA1_C in DPN while all other parameters show a negative association [Table 3].

Table 3: Correlation of fasting plasma glucose, postprandial plasma glucose, and glycosylated hemoglobin with the pulmonary function test in patients of Type 2 diabetes mellitus with and without neuropathy

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Multiple linear regression analysis for independent factor with forced expiratory volume at the 1^st s

[Table 4] shows the multivariate linear regression analysis for independent factors associated with % FEV₁, in patients of T2DM with neuropathy and without neuropathy. The standardized β weights of FPG, PPG, and HbA1_C show significant values in patients of DPN.

Table 4: Multivariate linear regression analysis for independent factors associated with forced expiratory volume in 1 s

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Discussion

Total 120 patients were included with female preponderance likely because of inclusion bias, as it is a hospital-based study. Patients with DN had a longer duration of diabetes, higher HbA1c, fasting glucose, and PPG which is expected as the prevalence of DN increases with the duration of DM.^[12],[26]

There was a significant difference in the mean value of FEV₁ and FVC and % FEV₁ in T2DM with DN when compared with T2DM without DN. No significant difference was observed in PEFR and FEF 25%–75% between both the groups. Many studies with a follow-up duration of more than 5 years demonstrated a rapid reduction in lung function in individuals with DM.^{[27],[28],[29],[30],[31]} These studies revealed that the reduction in FEV₁ is 2–3 times quicker in patients with DM when compared with nondiabetic and nonsmoker individuals.^{[27],[28],[29],[30],[31]} Along with the decline in FEV, decline in the FVC and dynamic compliance of lung has been reported in some studies.^{[32],[33],[34]} A more severe decline in the lung function in patients with DN in our study might be secondary to poor glycemic control and increased duration of diabetes. FPG and HbA1c were positively correlated with % FEV1 (r = 0.474, P = 0.008 and r = 0.588, P = 0.001, respectively) in patients with diabetes and neuropathy. Multivariate linear regression analysis of our data shows that HbA1_C, FPG, and PPG are closely associated with FEV₁ in DN patients. It indicates that glycemic change is an independent factor causing respiratory derangement in patients of DN. The presence of neuropathy per se might be contributing to the poor lung function in patients of DM with DN in our study. A reduction in respiratory muscle strength in patients of DM secondary to faulty muscle metabolism^{[35],[36],[37]} has been reported in recent literature. The reduced strength of the respiratory muscles in diabetic patients negatively correlates with the degree of glycemic control.^[35] Involvement of phrenic nerve modifies bronchial responsiveness leading to respiratory muscle dysfunction in DM patients.^[38] Recently, a systematic review has revealed a negative correlation between respiratory function and plasma glucose levels and the degree and duration of hyperglycemia.^[8] Strength of respiratory muscle has a strong correlation with pulmonary function, which depends upon the robust neural circuitry that controls the interaction between respiratory muscles and pulmonary function to preserve normal ventilation.^[39]

Nonvolitional gold-standard phrenic nerve stimulation in T2DM patients has revealed impairment of respiratory neuromuscular function strongly correlated to DN.^[40] Similarly, respiratory muscle weakness has been reported to be associated with autonomic neuropathy in patients of DM.^[41],[42] In contrast to available literature assessing peripheral muscle weakness in T2DM patients with DN,^{[3],[5],[7],[18],[19],[20],[21]} there is a paucity of data regarding the impact of DN on respiratory muscle strength.^[4] Diabetes per se decreases the pulmonary function,^[43],[44] but DN causes a major decrease, and it may be due to the more severe involvement in lungs in these patients.

A decline in the diffusing capacity for carbon monoxide has been found in the lung of patients with DM.^{[31],[32],[33]} This phenomenon can ascribe to increased thickness of the basal lamina of capillaries in the pulmonary circulation, decline in the volume of blood in the capillaries of pulmonary circulation, presence of autonomic neuropathy, and presence of advanced glycation end-product oxidative stress in the pulmonary endothelium.^{[12],[34],[35],[36],[37],[38]}

Conclusion

The present study highlighted a novel finding that DN is associated with decreased pulmonary function as compared to patients of diabetes without neuropathy. We also found that glycemic status of patients may adversely affect % FEV₁. Thus, proper control of hyperglycemia will decrease the further progression of disease. We also suggest to perform PFT in patients of DM with DN in the preoperative period so as to optimize the perioperative care. We suggest that further studies directed toward the finding of exact pathogenesis which causes pulmonary derangement should be conducted, which would further enhance understanding of disease and help in modifying the disease progression.

Financial support and sponsorship

This work was supported by the ICMR STS 2019 program.

Conflicts of interest

There are no conflicts of interest.

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