Skip to main content

The relationship between glycated hemoglobin A1c levels and exacerbation status in the patients with chronic obstructive pulmonary disease

Abstract

Objective

This study was performed in Razi Hospital, Rasht, Iran, between March 2016 and August 2018 on a population of chronic obstructive pulmonary disease (COPD) patients (56 as COPD exacerbation group and 56 as COPD stable group). Study variables include age, sex, occupation, body mass index (BMI), cigarette consumption, duration of COPD, annual hospitalization, dyspnea, glycated hemoglobin (HbA1c), FEV1, and FEV1/FVC indices.

Result

The mean age of the participants was 63.92 ± 10.75 years. There was a significant difference in the hospitalization between the patients with both exacerbation and normal state of COPD (P ≤ 0.001). HbA1c in the patients with exacerbation of COPD was significantly higher than stable status (P = 0.001). Logistic regression showed that HbA1c levels and hospitalization were predictors of exacerbation of COPD. HbA1c levels were statistically significant in terms of hospitalization in patients with COPD exacerbation. There was a significant difference between the HbA1c levels and MMRC in patients with COPD. The percentage of HbA1c was associated with exacerbation of COPD and HbA1c is a good predictor of disease severity in patients with COPD. It also shows that patients with COPD exacerbation and severe COPD are at the higher risk of hyperglycemia.

Introduction

Chronic obstructive pulmonary disease (COPD) is a Clinical status in which the airways become swollen and narrow and lead to damage to the alveoli. The disease is characterized by airflow restriction [1, 2]. The prevalence of the disease is generally estimated to be 5% [3]. It is estimated that 10% of Iranians have COPD [4]. The main feature of COPD is lung inflammation, which increases with the progression of the disease [5]. Pulmonary comorbidity affects the Prognosis of patients with COPD. Hyperglycemia is seen in 89% of COPD patients during acute respiratory failure who require mechanical ventilation [6, 7]. 50–80% of patients with exacerbation of COPD suffer from diabetes and are commonly hyperglycemic. This results in longer hospital stays and higher mortality compared to non-diabetic patients [8, 9]. There are various causes of hyperglycemia in COPD patients, including the use of beta-adrenergic drugs and glucocorticoids [10,11,12]. Other factors such as stress, the pre-exacerbation status of health, systemic features of the disease, inflammatory markers [13, 14], hypoxia [15], and oxidative stress may also be mentioned. Recent studies have shown that HbA1c, which controls basal blood glucose levels, can be a good biomarker for the diagnosis of high-risk diseases [16,17,18,19,20]. In fact, plasma levels of HbA1C in the blood, indicating fasting and postprandial glycemia over a period of 2 to 3 months, are widely used as a long-term marker of glucose [21].

There has been no extensive study on patients with exacerbation of COPD and its consequences in Iran. We hypothesized in this study that HbA1c levels are correlated with COPD severity. As a result, plasma HbA1C may be used as an indicator to predict the clinical status of patients with COPD. The results of this study can also be used to determine the exacerbation status of patients with COPD as a risk factor for pre-diabetes status.

Patients and methods

Study design, categorize of patients, and sample size

This cross-sectional study was performed on a population of patients with COPD who referring to Razi Hospital and specialized clinics in Rasht, Iran, between March 2016 and August 2018. Patients with COPD were given the necessary explanations about the purpose of the study and were entered into the study after obtaining informed consent. The diagnosis of COPD in participants was based on the spirometry (JAEGER; Vyntus SPIRO PC spirometer) finding of the “Razi Hospital Respiratory Test Unit” and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. In this study, modified medical research council (MMRC) questionnaire was used for grading dyspnea. The severity of the disease was determined according to GOLD criteria [20]. Patients were divided into four groups of mild, moderate, severe, and very severe obstruction based on spirometric criteria.

Diagnosis of exacerbation COPD and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were determined based on the patient’s clinical manifestations, such as aggravated dyspnea, cough, sputum production, and greater use of maintenance treatments, or complementary therapies. In this study, the criteria for COPD exacerbation were dyspnea exacerbation, respiratory distress, hypoxemia (PaO2 < 60 mmHg), and hypercapnia (PaO2 > 60 mmHg). Interventional or non-intervention mechanical ventilation was required. Staging COPD and the risk of exacerbation were determined according to GOLD criteria. Next, patients were divided into high-risk (C and D) and low-risk (A and B). The normal range for the HbA1C level is between 4% and 5.6%. HbA1C levels between 5.7% and 6.4% show a higher chance of getting diabetes. HbA1C levels of 6.5% or higher also show diabetes. In addition, HbA1C level was measured in Razi Hospital Laboratory, Rasht, Iran, using ELISA method (PishtazTeb, Iran). Sample size was estimated at least 56 participants in each group (95% confidence and 90% test power) based on a study of Haruka et al. [8]. Based on spirometry findings, patients with COPD whose FEV1 / FVC ratio was less than 70%, also with irreversible airway obstruction were included. Patients also with mild, moderate, severe, and very severe obstruction as well as exacerbation COPD were included. In the current study, patients were not included who needed admission to the intensive care unit (ICU). Patients were not included with diabetes, hypoglycemia, diabetic ketoacidosis, hyperglycemic, acute clinical need for intervention and blood transfusion, hemoglobinopathy, Iron deficiency anemia, uremic status, opacity chest X-ray (CXR), and prolonged oral corticosteroid. Patients were excluded who did not wish to enter the study and those who were unable to perform a breath test. Finally, patients were divided into intervention group (Group 1) and control group (Group 2). In the group 1, 56 patients were assigned with COPD exacerbation and AECOPD. In the Group 2, 56 patients were assigned with COPD stable. Spirometry findings and the number of hospitalizations were recorded for the last year of patients with COPD stable.

Statistical analysis

Variables of the current study Include; age, sex, occupation, body mass index (BMI), cigarette consumption, duration of COPD, annual hospitalization, dyspnea, glycated hemoglobin (HbA1c), FEV1, and FEV1/FVC indices. Mann Whitney and Kruskal Wallis nonparametric tests were used to comparing quantitative variables with abnormal distribution. Chi square tests were used to compare the qualitative variables. Spearman correlation coefficient was used to determine the correlation between variables. Sionel Logistic analyzer was performed to determine the variables related to disease severity. Significance levels of tests were ≤ 0.005 in this study.

Results

The mean age of the participants was 63.92 ± 10.75 years. According to Table 1, there was a significantly different in the hospitalization between the patients with exacerbation of COPD and patients with COPD in a stable status (P ≤ 0.001) (Table 1). The results of this study showed that HbA1c (5.6%) in the patients with exacerbation of COPD was significantly higher than in the patients with COPD in the stable status (P = 0.001). Logistic regression showed that HbA1c levels and hospitalization were predictors of exacerbation of COPD (P ≤ 0.05). Therefore, the exacerbation of COPD was increased to 4.45-fold with an increase in HbA1c levels (P ≤ 0.001). Based on the results, HbA1c levels in terms of severity status of airflow limitation (GOLD) in COPD patients were statistically significant (P = 0.001). According to the GOLD, there was a significant difference between D, A and B groups. As Table 2 shows, there was no significant difference between the HbA1c levels and FEV1 in patients with COPD (P value = 0.076). The study also showed that HbA1c levels were statistically significant in terms of hospitalization in patients with COPD (P = 0.022). Also, there was a significant difference between the HbA1c levels and MMRC in patients with COPD (P = 0.007). There was a significant difference between group 1 and group 3 (Table 2).

Table 1 Demographic characteristics of the patients with COPD exacerbation and stable status
Table 2 HbA1c status in patients with COPD base on the intensity of air flow restriction in the GOLD; FEV1, MMRC (n = 112)

According to the results of the study, there was a weak significant correlation between HbA1c levels and MMRC in patients with COPD (Spearman’s Correlation Coefficient, r = 0.197, P = 0.19). Also, there was no significant correlation between HbA1c levels and FEV1, FEV1 / FVC and duration of disease in patients with exacerbation of COPD. Also, HbA1c levels were not significantly correlated with FEV1, FEV1 / FVC and disease duration in patients with COPD in the stable status (Table 3).

Table 3 Correlation of glycosylated hemoglobin (HbA1c) with the forced expiratory volume in one second (FEV1), FEV1/ forced vital capacity (FVC) and duration of disease in patients with COPD exacerbation, and stable status

Discussion

Chronic obstructive pulmonary disease is one of the leading causes of mortality worldwide and its prevalence is likely to increase in the next twenty years [22]. Glucose metabolism disorders are more prevalent among COPD patients. Recent evidence has shown that diabetes can lead to COPD prognosis [23]. Recent studies have shown that high HbA1c levels, which control basal blood glucose levels, are a good biomarker for the diagnosis of serious diseases [16, 20]. Plasma HbA1C levels, which indicate fasting and postprandial glycemia over 2 to 3 months, have been widely used as a long-term marker of glucose regulation [24]. In this study, the frequency of hospitalization in patients with exacerbation of COPD was more than that of the Stable group, and this difference was statistically significant (P ≤ 0.001) (Table 1). Also, the frequency of exacerbation (twice a year or more) was higher in patients with exacerbation of COPD than in patients with COPD in stable status (P ≤ 0.05). In this study, HbA1c levels were significantly higher in patients with exacerbation of COPD in terms of GOLD.

In the present study, the percentage of glycosylated hemoglobin (HbA1c) by disease severity based on FEV1 levels in COPD patients was not statistically significant (P = 0.076). In the Stojkovikj et al., study [25], the prevalence of diabetes mellitus in all COPD patients was severe and very severe, 21%. In this study, in the group with very severe COPD, the median HbA1c was significantly higher than in the group with severe COPD. This is consistent with our results. Yang’s study [26] also showed that changes in HbA1c levels were significantly correlated with COPD severity. Other studies have also shown that patients with diabetes, FVC, FEV1, maximal expiratory flow (PEF), and reduced vital capacity (VC) had more obstructive or deleterious patterns than other patients [27, 28]. The study showed a U-shaped relationship between HbA1c and the incidence of COPD [29]. It has been shown that the risk of COPD is higher among people who have HbA1c levels below 6% or greater than 10% than those with HbA1c levels between 6% and 7%. Similar to the results in this study, found no difference in the prevalence of diabetes in patients with PFEV1 compared with patients who did not find PFEV1 [30]. However, a similar study by Baba et al. [31] showed that PFEV1 / FVC was associated with HbA1c. According to the Baba study patients with high glucose (100 ≤ FPG mg / dl and 5.6% HbA1c) had the lowest FEV1: FVC ratio [25]. Specifically, individuals with an FEV1/FVC index are significantly higher than HbA1c. This difference may be due to differences in host populations as well as the difference in severity of COPD in the population. In addition, non-diabetics may have a history of diabetes. Because consuming glucose-lowering drugs can hurt performance, research has shown that patients with type 2 diabetes who have HbA1c levels above 10% or below 6% are at a significantly increased risk of COPD [29]. Researchers have found that corticosteroid-consuming patients with acute respiratory failure (ARF) have significantly lower HbA1c levels and a longer hospital stay than patients who do not take corticosteroids [26]. According to our results, the percentage of HbA1c is positively correlated with the severity of COPD, which also increases with the increase in HbA1c percentage of COPD. Therefore, it seems that HbA1c can be used to predict the status of COPD patients and vice versa, using COPD severity as an indicator to predict pre-diabetic conditions. Despite these results, the impact of HbA1c percentages on pulmonary function parameters (and vice versa) is not well understood.

The strength of this study was evaluating dyspnea grade and severity of the disease by MMRC and GOLD criteria, respectively. Furthermore, future studies are expected to better investigate the prevalence of diabetes in the COPD population, its association with pulmonary parameters, and the association with the prognosis of patients with COPD without a history of diabetes.

Conclusion

Our findings represented that the percentage of HbA1c was associated with exacerbation of COPD and that HbA1c was a good predictor of disease severity in patients with COPD. It also shows that in our study patients with exacerbated COPD and those with severe involvement‌ are more at risk for hyperglycemia.

Limitations

In this study, healthy subjects were not included in the control group to more accurately examine the variables and indices. Also, another limitation of this study were the limited sample size, some incomplete patients’ clinical data, and lack of follow-up of patients.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

COPD:

Chronic obstructive pulmonary disease

GOLD:

Global Initiative for Chronic Obstructive Lung Disease

MMRC:

Modified Medical Research Council

AECOPD:

Acute Exacerbations of Chronic Obstructive Pulmonary Disease

ICU:

Intensive care unit

References

  1. Dwyer JT, Larive B, Leung J, Rocco M, Burrowes JD, Chumlea WC, et al. Nutritional status affects quality of life in Hemodialysis (HEMO) Study patients at baseline. J Ren Nutr. 2002;12(4):213–23.

    Article  Google Scholar 

  2. Harth L, Stuart J, Montgomery C, Pintier K, Czyzo S, Hill K, et al. Physical therapy practice patterns in acute exacerbations of chronic obstructive pulmonary disease. Can Respir J. 2009;16(3):86–92.

    Article  Google Scholar 

  3. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Respirology. 2017;22(3):575–601.

    Article  Google Scholar 

  4. Halvani GH, Zare M, Halvani A, Barkhordari A. Evaluation and comparison of respiratory symptoms and lung capacities in tile and ceramic factory workers of Yazd. Arh Hig Rada Toksikol. 2008;59(3):197–204.

    Article  Google Scholar 

  5. Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J. 2003;21(2):347–60.

    Article  CAS  Google Scholar 

  6. Edriss H, Selvan K, Sigler M, Nugent K. Glucose Levels in Patients With Acute Respiratory Failure Requiring Mechanical Ventilation. J Intensive Care Med. 2017;32(10):578–84.

    Article  Google Scholar 

  7. Flattet Y, Garin N, Serratrice J, Perrier A, Stirnemann J, Carballo S. Determining prognosis in acute exacerbation of COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:467–75.

    Article  CAS  Google Scholar 

  8. Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL, Wood DM, et al. Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax. 2006;61(4):284–9.

    Article  CAS  Google Scholar 

  9. Koskela HO, Salonen PH, Niskanen L. Hyperglycaemia during exacerbations of asthma and chronic obstructive pulmonary disease. Clin Respir J. 2013;7(4):382–9.

    Article  CAS  Google Scholar 

  10. Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33(4):289–94.

    Article  CAS  Google Scholar 

  11. Ho TW, Huang CT, Ruan SY, Tsai YJ, Lai F, Yu CJ. Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality. PLoS One. 2017 Apr 14;12(4):e017579.

  12. Dawson KP, Penna AC, Manglick P. Acute asthma, salbutamol and hyperglycaemia. Acta Paediatr. 1995;84(3):305–7.

    Article  CAS  Google Scholar 

  13. McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001;17(1):107–24.

    Article  CAS  Google Scholar 

  14. Kavanagh BP, McCowen KC. Clinical practice. Glycemic control in the ICU. N Engl J Med. 2010;363(26):2540–6.

    Article  CAS  Google Scholar 

  15. Oltmanns KM, Gehring H, Rudolf S, Schultes B, Rook S, Schweiger U, et al. Hypoxia causes glucose intolerance in humans. Am J Respir Crit Care Med. 2004;169(11):1231–7.

    Article  Google Scholar 

  16. Chen PC, Liao WI, Wang YC, Chang WC, Hsu CW, Chen YH, et al. An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients With Community-Acquired Pneumonia. Med (Baltim). 2015;94(34):e1456.

    Article  CAS  Google Scholar 

  17. Liao WI, Lin CS, Lee CH, Wu YC, Chang WC, Hsu CW, et al. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction. Sci Rep. 2016;6:27770.

    Article  CAS  Google Scholar 

  18. Liao W-I, Sheu WH-H, Chang W-C, Hsu C-W, Chen Y-L, Tsai S-H. An elevated gap between admission and A1C-derived average glucose levels is associated with adverse outcomes in diabetic patients with pyogenic liver abscess. PLoS ONE. 2013;8(5):e64476.

    Article  CAS  Google Scholar 

  19. Liao WI, Wang JC, Chang WC, Hsu CW, Chu CM, Tsai SH. Usefulness of Glycemic Gap to Predict ICU Mortality in Critically Ill Patients With Diabetes. Med (Baltim). 2015;94(36):e1525.

    Article  CAS  Google Scholar 

  20. Roberts GW, Quinn SJ, Valentine N, Alhawassi T, O’Dea H, Stranks SN, et al. Relative hyperglycemia, a marker of critical illness: introducing the stress hyperglycemia ratio. J Clin Endocrinol Metab. 2015;100(12):4490–7.

    Article  CAS  Google Scholar 

  21. Moghaddam MM, Keymoradzadeh A, Ghorbandoust R. The effect of non-surgical periodontal therapy on glycemic control and C1-reactive protein levels among type 2 diabetic patients with periodontitis: A clinical trial. J Curr Biomedical Rep. 2021 Mar;2(1)(6):32–7.

    Article  Google Scholar 

  22. Papaetis GS, Anastasakou E, Orphanidou D. Chlamydophila pneumoniae infection and COPD: more evidence for lack of evidence? Eur J Intern Med. 2009;20(6):579–85.

    Article  Google Scholar 

  23. Glaser S, Kruger S, Merkel M, Bramlage P, Herth FJ. Chronic obstructive pulmonary disease and diabetes mellitus: a systematic review of the literature. Respiration. 2015;89(3):253–64.

    Article  Google Scholar 

  24. Rahbar S. The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. Ann N Y Acad Sci. 2005;1043(1):9–19.

    Article  CAS  Google Scholar 

  25. Stojkovikj J, Zafirova-Ivanovska B, Kaeva B, Anastasova S, Angelovska I, Jovanovski S, et al. The Prevalence of Diabetes Mellitus in COPD Patients with Severe and Very Severe Stage of the Disease. Open Access Maced J Med Sci. 2016;4(2):253–8.

    Article  Google Scholar 

  26. Yang CJ, Liao WI, Tang ZC, Wang JC, Lee CH, Chang WC, et al. Glycated hemoglobin A1c-based adjusted glycemic variables in patients with diabetes presenting with acute exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;12:1923–32.

    Article  CAS  Google Scholar 

  27. Davis TM, Knuiman M, Kendall P, Vu H, Davis WA. Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Res Clin Pract. 2000;50(2):153–9.

    Article  CAS  Google Scholar 

  28. Davis WA, Knuiman M, Kendall P, Grange V, Davis TM. Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care. 2004;27(3):752–7.

    Article  Google Scholar 

  29. Li CI, Li TC, Liu CS, Lin WY, Chen CC, Yang SY, et al. Extreme values of hemoglobin a1c are associated with increased risks of chronic obstructive pulmonary disease in patients with type 2 diabetes: a competing risk analysis in national cohort of Taiwan diabetes study. Med (Baltim). 2015;94(1):e367.

    Article  CAS  Google Scholar 

  30. Mekov EV, Slavova YG, Genova MP, Tsakova AD, Kostadinov DT, Minchev DD, et al. Diabetes Mellitus Type 2 in Hospitalized COPD Patients: Impact on Quality of Life and Lung Function. Folia Med (Plovdiv). 2016;58(1):36–41.

    Article  CAS  Google Scholar 

  31. Baba S, Takashima T, Hirota M, Kawashima M, Horikawa E. Relationship between pulmonary function and elevated glycated hemoglobin levels in health checkups: A cross-sectional observational study in Japanese participants. J Epidemiol. 2017;27(11):511–5.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank all individuals who volunteered to participate in this study. Furthermore, thank you to hospital staff and specialists for assistance with conforming and recording cases.

Funding

No funding.

Author information

Authors and Affiliations

Authors

Contributions

Concept and study design: Alireza Jafarinezhad, Behrang Motamed. Methods, data collection and experimental work: Ali Alavi Foumani, Azita Tangestaninezhad, Mohammad Almasi. Results analysis and conclusions: Behrang Motamed, Ali Alavi Foumani, Azita Tangestaninezhad, Mohammad Almasi, Niloofar Faraji, Alireza Jafarinezhad. Manuscript preparation and editing: Niloofar Faraji, Alireza Jafarinezhad. All authors have read and approved the final version of the manuscript

Corresponding author

Correspondence to Alireza Jafarinezhad.

Ethics declarations

Ethics approval and consent to participate

All subjects gave their verbal informed consent to participate in the study, which was approved by the ethical committee at the Guilan University of Medical Science [IR.GUMS.REC.1397.378].

Consent for publication

N/A.

Competing interests

No potential conflict of interest was reported by the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Motamed, B., Alavi Foumani, A., Tangestaninezhad, A. et al. The relationship between glycated hemoglobin A1c levels and exacerbation status in the patients with chronic obstructive pulmonary disease. BMC Res Notes 15, 326 (2022). https://doi.org/10.1186/s13104-022-06217-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13104-022-06217-7

Keywords

  • Glycated hemoglobin A
  • Pulmonary Disease
  • Chronic obstructive