Association between Forced Vital Capacity and Neutrophil to Lymphocyte Ratio in Type 2 Diabetes Mellitus
R. Abiramasundari1, B. Dharani2*, S. Sugantha Priya3, R. Shanthini4
1Stanley Medical College and Hospital, Chennai, India.
2A.C.S Medical College and Hospital, Dr. M.G.R. Educational and Research Institute, Chennai, India.
3Mannargudi GH, Thiruvarur, India.
4Directorate of Medical Education, Chennai, India.
*Corresponding Author E-mail: doctordharanibhaskaran@gmail.com
ABSTRACT:
Background: Aim: To study the association between forced vital capacity and neutrophil to lymphocyte ratio in type 2 diabetes mellitus. Objectives: To measure FVC in T2DM patients. To assess the Neutrophil to Lymphocyte ratio in T2DM patients. To determine the correlation between FVC and NLR in T2DM patients. Materials and methods: A Cross-sectional study was done on 90 type 2 diabetes mellitus patients. Inclusion criteria include Subjects who fit into the diagnostic criteria of Type 2 diabetes mellitus and a known case of diabetes mellitus within 10 years of duration on regular treatment, Age – 30-50yrs, Both gender and Healthy volunteers. Exclusion criteria include Age > 50yrs, H/O acute or chronic respiratory disease, H/O acute or chronic cardiorespiratory disease, Smoker, H/O tobacco chewing, H/O hypertension, BMI > 30, Pregnancy, H/O spinal or thoracic cage deformity, Past H/O abdominal or thoracic surgery, H/O connective tissue disorders, H/O cancer and H/O Neuromuscular disease. Complete blood count was done to assess neutrophil to lymphocyte ratio. PFT was done to measure FVC. The correlation between FVC and NLR was done. Results: A negative correlation was found between FVC and NLR in diabetic participants which was statistically significant Conclusion: The present study shows that as NLR increases, the forced vital capacity also decreases in T2DM. Hence, NLR along with FVC can be assessed during routine follow up of diabetic patients for early diagnosis of lung function abnormality in T2DM.
KEYWORDS: Type 2 Diabetes Mellitus, Forced Vital Capacity, Neutrophil to Lymphocyte Ratio, Chronic Inflammation, Pulmonary function test, Lung function.
INTRODUCTION:
Diabetes Mellitus has been described as a chronic disease resulting from increased blood glucose levels due to relative or absolute lack of insulin or resistance to insulin. In Type 1 diabetes, there is a loss of insulin production due to beta cell destruction1.
Type 2 diabetes is a state of Insulin resistance or defective insulin production. Insulin is known as an anabolic hormone and its abnormalities can affect metabolism of protein, carbohydrate and fat. It has a major impact on well-being and lives of individuals and families worldwide.
The prevalence of diabetes mellitus has been on surge due to various factors such as unhealthy diet patterns, socio-economic development, sedentary lifestyle and ageing population. A proper educational intervention has proven to decrease the BMI in type 2 diabetic patients 2. Studies have shown that physical activity has reduced HbA1C level3. The symptoms which are associated with hyperglycemia includes polyuria, polyphagia, polydipsia, excessive tiredness, blurred vision, weight loss or weight gain4.
It was estimated that around half a billion people worldwide are living with diabetes mellitus. The estimated global prevalence was around 9.3% (463 million) in 20195. This prevalence is expected to increase by around 25% in 2030 and 51% in 20456. The distribution of prevalence was found to be higher in urban population (10.8%) when compared to rural population (7.2%). This was attributed to high prevalence among high-income countries (10.4%) when compared to low-income countries (4.0%). It was also found that occupational stress has also contributed to the development of type 2 diabetes mellitus which could be due to adverse psychological factors7,8. In recent years, increasing cases of type 2 diabetes mellitus among young individuals has contributed to high overall prevalence rate because of their longer survival. But it significantly affects their quality of life9.
Numerous studies are being conducted now a days to find out the deleterious effect of hyperglycemia on lung function in type 2 diabetic individuals. Lungs have a rich blood supply. Chronic hyperglycemia in type 2 diabetes mellitus can lead to non-enzymatic glycosylation of collagen and elastin in the lungs. This causes thickening of the basement membrane and microangiopathy. Hence because of this kind of detrimental effect of hyperglycemia on microvasculature, the pulmonary function gets affected in type 2 diabetes mellitus10.
Spirometry is an instrument used to quantify and identify functional abnormalities of the respiratory system11. It measures FVC, FEV1, VC, FEV1/FVC ratio and PEF. Forced Vital Capacity (FVC) is defined as the maximum amount of air which can be exhaled when blowing out as fast as possible12. FVC is reduced in restrictive pattern of lung diseases.
Neutrophil to Lymphocyte ratio (NLR) is an inexpensive, easily measured and reproducible marker of subclinical inflammation. It indicates impaired cell-mediated immunity due to systemic inflammation13. Type 2 diabetes mellitus is a state of chronic inflammation leading to complications14. NLR has been used as an indicator of systemic inflammation.
Hence, the aim of this current study is to find out the association between Forced vital capacity and Neutrophil to Lymphocyte ratio in Type 2 Diabetes Mellitus.
OBJECTIVES:
To assess Neutrophil to lymphocyte ratio in type 2 diabetes mellitus. To measure forced vital capacity in type in diabetes mellitus. To find out the association between forced vital capacity and Neutrophil to lymphocyte ratio in type 2 diabetes mellitus.
MATERIALS AND METHODS:
The present study was conducted after obtaining Institutional Ethical Committee clearance. The duration of the study was 1 year which consists of 90 study participants. It includes 30 control subjects, 30 subjects with duration of T2DM on regular treatment ≤ 5years (Group I) and 30subjects with duration of T2DM on regular treatment >5 to 10years (Group II). The study participants with T2DM were selected from outpatient of Diabetology department who fits under World Health Organization criteria of T2DM with fasting blood sugar(FBS) ≥126mg/dl and postprandial blood sugar (PPBS) ≥200mg/dl and HbA1C≥6.5%. It was a case control study.
A detailed history was collected through a proforma which contains basic details, past illness history, treatment history and family history to rule out individuals who comes under exclusion criteria.
Measurements like height, weight, waist circumference and BMI were recorded. BMI was calculated. As per JNC 7 criteria, all the subjects were recorded BP and screened for hypertension. All the basic investigations were performed like ECG, Chest X-Ray and Echo for ruling out any chronic respiratory or cardiac illness. All the normal subjects who are the attendants were screened in the same way. Blood pressure was recorded using Sphygmomanometer both supine and in standing position. Subjects with hypertension were excluded. All the subjects were screened for postural hypotension.
Inclusion criteria:
· Subjects who fit into the diagnostic criteria of Type 2 diabetes mellitus and a known case of diabetes mellitus within 10 years of duration on regular treatment.
· Age – 30-50yrs.
· Both gender
· Healthy volunteers.
Exclusion criteria:
· Age > 50yrs.
· H/O acute or chronic respiratory disease.
· H/O acute or chronic cardiorespiratory disease.
· Smoker.
· H/O tobacco chewing.
· H/O hypertension.
· BMI > 30.
· Pregnancy.
· H/O spinal or thoracic cage deformity.
· Past H/O abdominal or thoracic surgery.
· H/O connective tissue disorders.
· H/O cancer.
· H/O Neuromuscular disease
Spirometery is said to be one of the non-invasive lung function tests that provides physiological confirmation of the diagnosis15. Spirometry was performed after asking the participant to remove the denture, loosen the tight clothes and making him relaxed. The pulmonary function parameters FEV1, FVC, FEV1/FVC and PEFR for the participants were recorded using “EASY ONE” spirometer and analyzed using EASY WARE 2.24.0.0” software. The subjects are made to do the procedure for atleast 3 times and the best of the three values was taken. The Predicted percentage value for each parameter were selected according to European Respiratory Society standards.
All the patients were done investigations like FBS, PPBS, RBS and HbA1c to find out the degree of hyperglycemia and also to select subjects. Using SYSMEX XP-300 Hematology-Analyzer, Complete Blood Count was measured by the principle of electrical impedance. Complete blood count was done to assess Neutrophil to Lymphocyte Ratio (NLR). The NLR levels in all groups were assessed and the clinical correlation of NLR levels and Forced Vital Capacity (FVC) was done.
Statistical analysis:
The study population was divided based on duration of disease into two groups:
· Group1: Type 2 diabetes mellitus subjects on regular treatment for ≤ 5years.
· Group2: Type 2 diabetes mellitus subjects on regular treatment for > 5 to 10 years.
Using SPSS software version 20, analysis of the data was done. Mean, Standard Deviation and p-value were calculated. The comparison of the Neutrophil to lymphocyte ratio and Forced vital capacity between the group1 and control group, group 2 and control group and group 1 and group 2 was done using student t test. P value of <0.05 was considered as statistically significant and p-value of <0.001 was considered as statistically highly significant. The association between the Neutrophil to lymphocyte ratio and Forced vital capacity in type 2 diabetes mellitus was studied using Pearson’s correlation test.
RESULTS AND DISCUSSION:
Using SPSS software version 20, the obtained data were analyzed. The control group include 30 normal healthy volunteers. The group I subjects include 30 type 2 diabetic individuals with duration of type 2 diabetes less than 5 years. The group II subjects include 30 type 2 diabetic individuals with duration of type 2 diabetes between 5 to 10 years. The anthropometric, lung function and biochemical parameters of the control and study groups were analyzed for mean and standard deviation.
Table 1 depicts the baseline characteristics and biochemical parameters of the subjects of control group, Group I and Group II. The average age of the control group subjects was 43years with SD of 4.6 and their average BMI was 27 with SD of 3.5655. The average HbA1C was found to be 4 with SD of 0.3965. The average fasting blood sugar level was found to 88mg/dl with SD of 9.9747, the postprandial blood sugar level was 115mg/dl with SD of 9.9417.
The average age of the group I subjects was 43years with SD of 5.2 and their average BMI was 26 with SD of 2.9395. The average HbA1C was found to be 6 with SD of 0.2840. The average fasting blood sugar level was found to 161mg/dl with SD of 35.6358, the postprandial blood sugar level was 228mg/dl with SD of 84.1321.
The average age of the group II subjects was 43years with SD of 4.1 and their average BMI was 27 with SD of 2.837. The average HbA1C was found to be 6.4 with SD of 0.2586. The average fasting blood sugar level was found to 186mg/dl with SD of 28.3262, the postprandial blood sugar level was 257mg/dl with SD of 25.3009.
Table 1: Baseline characteristics and biochemical parameters
|
|
Control Group (n=30) |
Group I (n=30) |
Group II (n=30) |
|||
|
Mean |
SD |
Mean |
SD |
Mean |
SD |
|
|
Age (yrs) |
43 |
4.6 |
43 |
5.2 |
43 |
4.1 |
|
Height (cm) |
158 |
4.688 |
158 |
4.6889 |
157 |
3.2816 |
|
Weight (Kg) |
68 |
8.684 |
67 |
7.0983 |
66 |
6.3644 |
|
BMI |
27 |
3.5655 |
26 |
2.9395 |
27 |
2.837 |
|
HbA1C (%) |
4 |
0.3965 |
6 |
0.2840 |
6.4 |
0.2586 |
|
FBS (mg/dl) |
88 |
9.9747 |
161 |
35.6358 |
186 |
28.3262 |
|
PPBS (mg/dl) |
115 |
9.9417 |
228 |
84.1321 |
257 |
25.3009 |
|
NLR |
1.3422 |
0.2822 |
1.953 |
0.81408 |
2.184 |
0.7259 |
Table 2: Comparison of baseline parameters between control group and group I subjects.
|
|
Control group (n=30) |
Group I (n=30) |
p-value |
||
|
|
Mean |
SD |
Mean |
SD |
|
|
Age (yrs) |
43 |
4.6 |
43 |
5.2 |
>0.05 |
|
Height (cm) |
158 |
4.688 |
158 |
4.6889 |
>0.05 |
|
Weight(Kg) |
68 |
8.684 |
67 |
7.0983 |
>0.05 |
|
BMI |
27 |
3.5655 |
26 |
2.9395 |
>0.05 |
|
HbA1c (%) |
4 |
0.3965 |
6 |
0.2840 |
<0.05 |
|
FBS (mg/dl) |
88 |
9.9747 |
161 |
35.6358 |
<0.05 |
|
PPBS (mg/dl) |
115 |
9.9417 |
228 |
84.1321 |
<0.05 |
Table 2 depicts the comparison of baseline parameters between control group and group I. It shows that the age, height, weight and BMI of the group I subjects was found to be similar with control group subjects and statistically not significant with p-value > 0.05. The p-value of biochemical parameters FBS, PPBS and HbA1C between control group and group I was found to be <0.05 which shows a statistically significant difference.
Table 3: Comparison of baseline parameters between control group and group II subjects.
|
|
Control group (n=30) |
Group II (n=30) |
p-value |
||
|
|
Mean |
SD |
Mean |
SD |
|
|
Age (yrs) |
43 |
4.6 |
43 |
4.1 |
>0.05 |
|
Height (cm) |
158 |
4.688 |
157 |
3.2816 |
>0.05 |
|
Weight (Kg) |
68 |
8.684 |
66 |
6.3644 |
>0.05 |
|
BMI |
27 |
3.5655 |
27 |
2.837 |
>0.05 |
|
HbA1c (%) |
4 |
0.3965 |
7.3 |
1.1602 |
<0.05 |
|
FBS (mg/dl) |
88 |
9.9747 |
186 |
28.3262 |
<0.05 |
|
PPBS (mg/dl) |
115 |
9.9417 |
257 |
25.3009 |
<0.05 |
Table 3 depicts the comparison of baseline parameters between control group and group II subjects. It shows that the age, height, weight and BMI of the group II subjects was found to be similar with control group subjects and statistically not significant with pvalue > 0.05. The p-value of biochemical parameters FBS, PPBS and HbA1C between control group and group II was found to be <0.05 which shows a statistically significant difference.
The p-value of FVC between control group and group I was 0.04 which was statistically significant.
The p-value of FVC between control group and group II was 0.032 which was statistically significant. The p-value of FVC between group I and group II were 0.021 which was statistically significant. This shows that most of the diabetic subjects have restrictive pattern of lung disease with increasing duration of type 2 diabetes mellitus.
Table 4: Comparison of NLR between control group subjects and group I subjects.
|
|
Control |
Group I |
p-value |
||
|
NLR |
Mean |
SD |
Mean |
SD |
0.0278 |
|
1.3422 |
0.2822 |
1.953 |
0.81408 |
||
Table 4 represents comparison of NLR between control group subjects and group I subjects. It shows that the p-value is 0.0278 which is statistically significant.
Table 5: Comparison of NLR between control group subjects and group II subjects.
|
|
Control |
Group II |
p-value |
||
|
NLR |
Mean |
SD |
Mean |
SD |
0.00707 |
|
1.3422 |
0.2822 |
2.184 |
0.7259 |
||
Table 5 represents the comparison of NLR between control group subjects and group II subjects. It shows that the p – value is 0.00707 which is statistically significant.
Table 6: Comparison of NLR between group I subjects and group II subjects.
|
|
Group I |
Group II |
p-value |
||
|
NLR |
Mean |
SD |
Mean |
SD |
0.00813 |
|
1.953 |
0.81408 |
2.184 |
0.7259 |
||
Table 6 represents the comparison of NLR between group I and group II subjects. It shows that the p-value is 0.00813 which is statistically significant. Hence, this shows that as the duration of type 2 diabetes mellitus increases, NLR also increases significantly.
Table 7: Correlation between FVC and NLR in group I and group II subjects.
|
|
r-value |
|
|
Group I (n=30) |
Group II (n=30) |
|
|
FVC |
-0.183458 |
-0.2356 |
|
NLR |
||
Table 7 represents correlation between FVC and NLR in group I and group II subjects. It shows a negative correlation between FVC and NLR in type 2 diabetic individuals. As the NLR increases, the FVC decreases with increasing duration of type 2 diabetes mellitus. The decreased FVC shows a restrictive pattern of lung disease along with increase in NLR.
The present study shows that most of that Forced Vital Capacity was reduced in diabetic subjects when compared to control group subjects. Many previous studies have evidenced that chronic inflammation in type 2 diabetes was associated with reduced pulmonary function in diabetic individuals with increasing duration of type 2 diabetes.
Type 2 diabetes is regarded as a lifelong condition that is associated with increased mortality and morbidity rates due to microvascular complications. The most common complications include diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and coronary artery disease. In elderly patients with diabetic neuropathy, factors such as dyslipidemia, CAD, HTN, and high BMI have contributed to its progression16. It was found that the duration of diabetes and comorbidities such as hypertension and dyslipidemia contribute to the progression of diabetic neuropathy17. Metabolic syndrome in type 2 diabetes mellitus often presents as liver diseases18. Additionally, oxidative stress-induced microangiopathy has been found to reduce pulmonary function in type 2 diabetes. It is estimated that when the duration of type 2 diabetes reaches 20 years, around 80% of type 2 diabetic individuals develop microvascular complications. Hence, the focus of medical care must be directed towards reducing the incidence of long-term complications associated with type 2 diabetes through proper routine screening. Studies have shown that effective DSME interventions can significantly improve the lifestyle of type 2 diabetic patients19. Also, a structured teaching program on knowledge about the management of type 2 diabetes mellitus has proven to be effective20.
The Neutrophil to lymphocyte ratio is most accessible and inexpensive inflammatory biomarker which can be calculated easily from complete Blood Count. It has low specificity and high sensitivity as it responds to inflammation and stress. It has proven to be useful in various cardiovascular diseases and inflammatory diseases21.
Chronic inflammation, indicated by an increased leukocyte count, plays a significant role in the development of microvascular and macrovascular complications in type 2 diabetes mellitus22. Type 2 diabetes mellitus is characterized by elevated levels of inflammatory markers such as cytokines and mean platelet volume23,24.
In the present study it is found that as the duration of type 2 diabetes mellitus increases, NLR also increases significantly. This indicates that Neutrophil to Lymphocyte ratio is a sensitive inflammatory marker in type 2 diabetes mellitus. Systemic inflammatory markers and mortality were interlinked and increased when both T2DM and CAD occur together25.
Tiruneh Adane et al in their study found that poor glycemic control in type 2 diabetes mellitus was significantly associated with high Neutrophil to Lymphocyte ratio26. They have described that increasing Neutrophil to lymphocyte ratio indicates the inflammatory burden in type 2 diabetes mellitus. It is due to the negative effect of neutrophil on endothelium leading to endothelial damage and lymphocyte are playing an anti-atherosclerotic role27. In recent literature, the glucose control was found to be associated with Neutrophil to Lymphocyte ratio in T2DM28.
Our present study has found that FVC decreases with the increasing duration of type 2 diabetes mellitus. Similar findings were observed in Aiswarya et al study29. They found that FEV1/FVC was negatively correlated to HbA1C. Jamatia et al also in their study reported that FVC and FEV1 has negative correlation with HbA1C30. In another study by kim et al, it was stated that lower levels of FEV1 and FVC were independently associated with HbA1C31. Anand et al also had similar findings in their study with negative correlation between HbA1C and PFT (P<0.05 and r=-0.390)32. Kaur and Agarwal in their study found that fasting blood sugar has positive correlation with FEV1/FVC in type 2 diabetes mellitus33.
CONCLUSION:
In the present study it has been found that elevated neutrophil to lymphocyte ratio was associated with decreased Forced vital capacity in type 2 diabetes mellitus. This shows that chronic inflammation in type 2 diabetes mellitus has an impact on lung function in type 2 diabetes mellitus.
Hence Neutrophil to lymphocyte ratio must be used as an investigation to assess the degree of inflammation along with spirometry in type 2 diabetes individuals during routine health care.
Regular breathing exercises should be recommended during routine healthcare check-ups for individuals with type 2 diabetes. These exercises can help improve lung function and overall respiratory health. Additionally, maintaining a healthy diet and receiving appropriate treatment to control blood sugar levels are essential to prevent chronic inflammation, which can lead to long-term complications such as lung impairment.
Early detection and primary prevention of pulmonary function impairment are crucial in reducing the mortality and morbidity rates among type 2 diabetic patients. Regular screenings and proactive measures can help identify lung issues early, allowing for timely intervention and management.
Moreover, it is important to take comprehensive initiatives to prevent the lungs from becoming a target organ for long-term complications in type 2 diabetes. This includes educating patients about the importance of lung health, implementing routine respiratory assessments, and integrating pulmonary care into diabetes management plans. By doing so, healthcare providers can effectively break the chain of chronic inflammation and protect individuals with type 2 diabetes from severe respiratory complications.
ACKNOWLEDGEMENTS:
We would like to extend our sincere gratitude to the patients who participated in this study. Your willingness to share your experiences and your commitment to improving our understanding of type 2 diabetes have been invaluable.
We also wish to thank the Department of Diabetology for their unwavering support and collaboration throughout this research. Your expertise, guidance, and resources have been crucial in making this study possible.
CONFLICT OF INTEREST:
Nil
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Received on 15.05.2024 Revised on 14.10.2024 Accepted on 01.01.2025 Published on 01.07.2025 Available online from July 05, 2025 Research J. Pharmacy and Technology. 2025;18(7):3330-3335. DOI: 10.52711/0974-360X.2025.00481 © RJPT All right reserved
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