Diabetes Control and Clinical Outcomes in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
1
Technion-Israel Institute of Technology, Department of Medicine, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
2
Institute of Endocrinology & Metabolism, Zvulon Medical Center, Clalit Health Services and Azrieli School of Medicine, Bar Ilan University, Safed 1311502, Israel
3
Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
*
Author to whom correspondence should be addressed.
Diabetology 2025, 6(7), 66; https://doi.org/10.3390/diabetology6070066
Submission received: 20 February 2025
/
Revised: 12 June 2025
/
Accepted: 24 June 2025
/
Published: 4 July 2025
Abstract
Background: Type 2 diabetes mellitus (T2DM) is common among patients with chronic obstructive pulmonary disease (COPD). We examined the association between glycemic control and clinical outcomes in patients with COPD exacerbation and T2DM. Methods: A retrospective study of patients with T2DM and COPD exacerbation comparing controlled (HbA1c < 7.5%) to uncontrolled (HbA1c ≥ 7.5%) glycemia prior to admission. The primary endpoint is defined as a composite of 6-month rehospitalization/mortality. Secondary endpoints included 6-month mortality and 6-month readmission. Results: Of 426 admissions, 179 (42%) had uncontrolled glycemia. The risk of rehospitalization/mortality was significantly increased in the uncontrolled group in univariate (HR1.6, 95%CI 1.11–2.3, p = 0.01) and multivariate (HR 1.82, 95%CI 1.24–2.67, p = 0.002) analyses. The risk of 6-month rehospitalization was increased in the uncontrolled group in both univariate (HR1.94, 95%CI 1.16–3.23, p = 0.011) and multivariate (HR1.98, 95%CI 1.19–3.27, p = 0.008) analyses. No difference was found between 6-month mortality risks. Conclusions: Optimal glycemic control may improve COPD management and reduce adverse outcomes.
1. Introduction
Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) are commonly encountered in clinical practice. The significant comorbidity of these two chronic disorders is associated with substantial increases in morbidity, mortality, and healthcare costs. The analysis of the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmissions Database revealed that 30.2% of COPD hospitalizations involved a T2DM diagnosis, resulting in increased complications, longer hospital stays, and higher costs [1]. The Shahrekord PERSIAN cohort study also found a 16.7% prevalence of this comorbidity in southwest Iran [2]. Another study using data from the Taiwan Longitudinal Health Insurance Database reported that 16% of COPD patients had pre-existing diabetes, and 19% developed incident diabetes over a 10-year follow-up period [3]. Additionally, a nationwide population-based study in Taiwan found that COPD patients had a significantly higher rate of incident type 2 diabetes compared to control subjects [4].
In a systematic review and meta-analysis by Peng et al., the risk of T2DM was significantly higher in patients with COPD with a relative risk of 1.25 [5]. These consistent findings across diverse populations underscores the need for integrated management strategies to address this clinically significant association and improve patient outcomes.
Several studies have highlighted the bidirectional relationship between COPD and T2DM. For instance, COPD can be considered a risk factor for the development of T2DM due to chronic inflammation, oxidative stress, and the use of corticosteroids, which can induce insulin resistance [6]. Other shared underlying factors such as aging, smoking, physical inactivity, and genetics might also contribute to the risk of T2DM and COPD comorbidity [7]. Zhu et al. used Mendelian randomization analyses to show a genetic correlation and bidirectional causal association between T2DM and pulmonary function. Their findings suggest that impaired lung function can increase the risk of T2DM, and vice versa, indicating a complex interplay between these conditions [8].
The use of inhaled or systemic corticosteroids in COPD is a risk factor for the development of T2DM. In a nationwide observational cohort study, Saeed et al. found that inhaled corticosteroids (ICS) were associated with a dose-dependent increase in the risk of new-onset T2DM in patients with COPD [9]. Price et al. also reported that ICS therapy in patients with COPD and comorbid T2DM led to significant increases in HbA1c values, indicating worsened diabetic control. This effect was more pronounced with higher cumulative doses of ICS [10].
Conversely, multiple studies have demonstrated that T2DM is associated with impaired pulmonary function. A meta-analysis by van den Borst et al. found that diabetes is associated with a modest but statistically significant reduction in pulmonary function, characterized by a restrictive pattern. This includes reductions in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) [11]. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) reported that Hispanics/Latinos with type 2 diabetes had lower mean FEV1 and FVC values and higher dyspnea scores compared to those without diabetes, suggesting functional and symptomatic pulmonary impairment [12]. A prospective study using UK Biobank data found that individuals with diabetes had a 35% higher risk of developing COPD compared to those without diabetes. Additionally, longer diabetes duration was associated with a higher risk of COPD and worse survival outcomes for COPD patients [13]. In patients with established diagnosis, T2DM can exacerbate COPD by increasing susceptibility to infections, worsening lung function, and contributing to systemic inflammation [14]. T2DM is associated with a higher risk of severe exacerbations and hospital readmissions in COPD patients. A study by Castañ-Abad et al. found that COPD patients with T2DM had a significantly higher risk of severe exacerbations and hospital admissions compared to those without diabetes [15]. Similarly, Belligund et al. reported that diabetes was associated with higher 30-day readmission rates following COPD-related hospitalizations [1]. Lin et al. showed that COPD patients with T2DM had longer hospital stays, lower arterial partial pressure of oxygen (PaO2), and higher troponin levels, indicating worse clinical status and prognosis [16].
T2DM also contributes to higher mortality rates in COPD patients. Ho et al. demonstrated that COPD patients with pre-existing T2DM had a significantly higher hazard ratio for mortality compared to those without diabetes [3]. Additionally, Raslan et al. found that COPD patients with T2DM had a higher rate of all-cause mortality and a 3.03-times higher rate of respiratory-cause mortality compared to those without COPD [17].
Comorbidities such as cardiovascular disease, hypertension, and obesity, which are prevalent in both COPD and T2DM, significantly complicate clinical management and necessitate a comprehensive approach to treatment, focusing on both the pulmonary and metabolic health of these patients. Cardiovascular disease can exacerbate COPD symptoms and complicate treatment due to overlapping symptoms like dyspnea and chest pain. Additionally, certain COPD medications, such as bronchodilators, may have cardiovascular side effects, necessitating careful management and monitoring [18,19]. Hypertension can worsen the prognosis of both COPD and T2DM by increasing the risk of cardiovascular events and complicating the management of blood pressure, especially in the context of polypharmacy. The presence of hypertension in COPD patients has been associated with a higher risk of hospitalizations and mortality [16,20]. Obesity further complicates the clinical management of COPD and T2DM due to its association with metabolic syndrome, increased systemic inflammation, and reduced lung function. Obese patients with COPD often have different comorbidities compared to non-obese patients, including a higher prevalence of hypertension and diabetes mellitus [21]. This necessitates a tailored approach to management, focusing on weight reduction, optimizing glycemic control, and addressing cardiovascular risk factors.
Despite the vast amount of literature on the relationship between T2DM and COPD, little is known about the association between glycemic control and the clinical outcomes of COPD exacerbation. In the current study, we examined the association between uncontrolled glycemia and major adverse clinical outcomes in patients with T2DM and who were admitted due COPD exacerbation.
2. Methods
We conducted a retrospective cohort study of patients with T2DM and COPD who were hospitalized due to COPD exacerbation at Carmel Medical Center, Haifa, Israel. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and approved by the Carmel Medical Center Institutional Review Board (IRB), approval code 0136-17-CMC dated 3 January 2018. All patient records were anonymized before analysis. Since this is a retrospective study that involved no interaction or intervention with patients, informed consent was not required, in accordance with Israeli Ministry of Health regulations.
Patients aged 35 years and above admitted between the years 2005 and 2017 were analyzed.
We excluded patients under systemic steroid therapy prior to admission and those with other possible diagnoses including pulmonary congestion, acute coronary syndrome, pneumonia, lung cancer, pulmonary embolism, or asthma.
Data was extracted from hospital and community medical databases. Demographics and clinical characteristics were collected including age, gender, co-morbidities, the use of home oxygen, inhaled corticosteroids, and/or inhaled bronchodilators.
Preadmission glycemic control was defined by the most recent HbA1c level within 12 months prior to admission. Patients were divided into two groups: controlled (HbA1c < 7.5%) and uncontrolled (HbA1c ≥ 7.5%). The primary endpoint was defined as the composite of 6-month readmission and/or mortality. Secondary endpoints included readmissions or mortality within 6 months. Adjustments for the above-mentioned potential confounders (demographic and comorbidities) were conducted if the differences between the study groups had a p-value of <0.1 in univariate analysis.
Continuous variables are summarized by mean ± standard deviation, and categorical variables are presented as numbers and proportions. Comparisons of baseline characteristics between the two groups were performed using the independent t-test or the Mann–Whitney test, as appropriate, for the continuous variables and the chi-square test for categorical variables.
Time to re-admission and/or mortality was estimated using Kaplan–Meier curves.
Correlation between HbA1c and study outcomes was evaluated using the cox proportional model with frailty terms to adjust for possible intra-patient correlations. Adjusted hazard ratios (Adj HR) with 95%CI are shown. Statistical analyses were performed using IBM SPSS Statistics 24.0 software (IBM, New York, NY, USA, and SAS 9.4). For all analyses, a p-value of 0.05 for the two-tailed tests was considered statistically significant.
3. Results
Baseline Patient Characteristics: A Total of 426 Patients Were Included in the Study
Demographic and clinical characteristics are presented in Table 1. In 247 (58.0%), preadmission HbA1c was <7.5% (controlled group); HbA1c ≥ 7.5% was in the uncontrolled group in 179 (42.0%) of hospitalizations. The mean age at admission was 73.2 ± 10.2 years with predominantly male patients (65.7%). The uncontrolled group was more likely to have ischemic heart disease (76.5% vs. 55.9%, p < 0.0001) and heart failure (HF) (64.8% vs. 49.8%, p = 0.002).
No significant difference was found between the groups in age, gender, hypertension, use of inhaled corticosteroids or bronchodilators, home oxygen therapy, frequency of mechanical ventilation, and mean length of hospital stays.
Primary endpoint—6-month rehospitalization/mortality: In 130 cases (30.5%), there was at least 1 re-admission or mortality in the following 6 months. Table 2 summarizes the univariate and multivariate analyses for the risk of rehospitalization/mortality for demographic and clinical parameters. The uncontrolled group had a higher risk of 6-month readmission/mortality at HR 1.60 95%CI (1.11–2.3), p = 0.010. Age was associated with a minor increase in the risk of readmission/mortality at HR 1.02 95%CI (1.00–1.04), p = 0.04. Home oxygen therapy was a prominent risk factor for readmission/mortality at HR 1.98 95%CI (1.37–2.88), p = 0.0003. We found no association between other demographic and clinical parameters and the risk of 6-month readmission/mortality. In multivariate analysis, the risk of 6-month readmission/mortality remained significantly increased in uncontrolled group at HR = 1.82 95%CI (1.24–2.67), p = 0.002, the use of home oxygen therapy at HR = 2.22CI (1.53–3.22), p < 0.0001) and age at HR = 1.02 (1.00–1.04), p = 0.036. A Kaplan–Meier survival function curves for controlled vs. uncontrolled T2DM and the 6-month rehospitalization/mortality composite endpoint are presented in Figure 1.
Secondary endpoints—Six-month rehospitalization risk: These results are presented in Table 3. In 73 (17.1%) cases, there was at least 1 re-admission in the following 6 months. The risk for 6-month readmission was increased in the uncontrolled group in both univariate (OR 1.94, 95% CI 1.16–3.23, p = 0.011) and multivariate (OR 1.98, 95%CI 1.3–19.27, p = 0.008) analyses.
Six-month mortality: We found no statistically significant difference in the risk of 6-month mortality between the controlled and uncontrolled groups (13.7% vs. 9%) at HR 1.37 95%CI (0.79–2.38), p = 0.263.
4. Discussion
We demonstrated that uncontrolled glycemia is present in 42% of T2DM patients and COPD exacerbation. We also found that the risk for a 6-month rehospitalization/mortality composite was increased in the uncontrolled group with no difference in the risk for 6-month mortality.
Inconsistent findings are reported in the literature regarding the clinical outcomes in COPD exacerbation and T2DM. Two prospective studies demonstrated an increased risk of readmission [22,23], while McGhan et al. reported decreased 1-year rehospitalizations [24]. Another study suggested that T2DM was associated with a higher rate of all cause rehospitalization but not admissions due to COPD exacerbation [25]. In a study by Roberts et al., T2DM was associated with both early (within 30 days) and late (within 180 days) COPD-related rehospitalizations [26]. Koskela et al. reported that diabetes was associated with a threefold increase in the risk of death during a median follow up of 6 years [27]. A further study analyzing data from the Healthcare Cost and Utilization Project (HCUP) reported that COPD patients with diabetes had higher rates of hospital readmissions, longer hospital stays, and increased healthcare costs compared to those without diabetes.
Our findings align with the association between uncontrolled glycemia and worse pulmonary function, which was demonstrated by Maan et al., who reported a significant inverse correlation between HbA1c levels and various lung function parameters, including FEV1 and FVC [28]. Similarly, the Atherosclerosis Risk in Communities (ARIC) study found that adults with diabetes had significantly lower predicted FVC and FEV1 values compared to non-diabetic individuals, and these differences persisted after adjusting for confounding factors [29]. Although diabetes was not associated with higher hospital mortality, it was linked to a greater need for home healthcare upon discharge [1]. These clinical findings align with previous reports on the association between elevated blood glucose levels and reduced pulmonary functions and the association between better glycemic control and improved alveolar capillary membrane gas transfer [13].
There are several possible mechanisms where chronic hyperglycemia increases rehospitalization and mortality through vascular damage and inflammation [30]. It causes endothelial dysfunction, oxidative stress, and adhesion molecule upregulation, promoting cardiovascular instability. It also accelerates atherosclerosis via AGEs and oxidative stress, increasing the risk of myocardial infarction and stroke [31]. Additionally, microvascular damage leads to nephropathy, retinopathy, and neuropathy, contributing to heart failure and infections [32]. Persistent inflammation and fibrosis further exacerbate organ injury, increasing the likelihood of adverse outcomes [33].
Hospitalizations with COPD and T2DM could be influenced by numerous factors including patient age and other comorbidities [34]. In our cohort, patients with uncontrolled T2DM tended to be younger but had a significantly higher proportion of ischemic heart disease and heart failure comorbidities. These comorbidities probably mitigated the “protective effect” that a younger age may exhibit in this group. Overall, the presence of these comorbidities requires an integrated and multidisciplinary approach to management, emphasizing the need for comprehensive care plans that address all aspects of the patient’s health to improve outcomes and quality of life [35].
Adherence for both COPD and diabetes treatments was not evaluated in our study. In that context, the increased rehospitalization in the uncontrolled group could be attributed to inadequate adherence to T2DM and COPD medications. Patients with advanced COPD are more commonly prescribed corticosteroids for longer periods with a resultant increased risk of developing hyperglycemia. In our cohort, we excluded patients with recent systemic corticosteroid therapy to limit the confounding effect of these medications. However, a “legacy effect” on glycemia due to prior corticosteroid treatment could not be ruled out in patients with more advanced COPD.
Our cohort consisted of hospitalized patients with COPD exacerbation who are presumed to have more advanced disease and therefore a relatively poorer prognosis. Thus, finding a significant favorable effect of better glycemic control in this cohort may have been more challenging. A larger cohort that includes COPD patients in a community setting may shed more light on the association between glycemic control and COPD-related adverse outcomes.
Ischemic heart disease and heart failure were more frequent in the uncontrolled group. For obvious reasons this finding could serve as a major confounder. However, in further analysis we found that these two comorbidities were not associated with worse outcomes (rehospitalization/mortality). This result could be explained by careful selection of patients and the exclusion of admissions that are related to these diseases (pulmonary congestion and acute coronary syndrome).
This is a retrospective study with multiple limitations. However, real-world data on T2DM and COPD exacerbation are valuable due to the large numbers of patients suffering from this disease combination and the scarcity of evidence on the effects of better glycemic control on the natural history of COPD. As we experienced in this study, careful data collection can be difficult regarding these two complex diseases. While the diagnosis of T2DM depends on measurements of blood glucose and HbA1c levels, COPD diagnosis is often more challenging. Since we could not retrieve spirometry records of our COPD patients (retrieving spirometry data for our cohort poses technical challenges, as these data reside in a different database outside our medical center and are not digitized), we had to rely on diagnoses given by a pulmonologist. Hence, the binary nature of the data collected could not enable risk stratification according to COPD severity. In this context, most patients admitted for COPD exacerbation suffer from a severe form of the disease. Consequently, our cohort is primarily composed of individuals with relatively advanced COPD. We were unable to retrospectively obtain the smoking status of patients hospitalized for COPD. The “smoker diagnosis” is often not regularly updated, and we wanted to avoid including patients who had previously smoked but may have since quit, without this change being reflected in their records. Moreover, a sizeable proportion of patients who have been diagnosed with COPD exacerbation had to be excluded, since their hospitalization could be attributed to other respiratory tract diseases, such as lung cancer, pneumonia, pulmonary congestion, or pulmonary embolism. We also did not perform a comparison of clinical characteristics between survivors and non-survivors, since there were no significant differences in the risk for 6-month mortality between the groups.
In conclusion, despite its retrospective design and limited clinical data, our study suggests that uncontrolled glycemia may be linked to increased risks of hospital readmission and the combined endpoint of readmission or mortality in patients with COPD and T2DM. Larger studies with expanded patient cohorts, longer follow-up, and comprehensive data—including concomitant medications, accurate smoking history, COPD severity with spirometry, and lung function data—are needed to better assess the impact of uncontrolled glycemia on clinical outcomes in COPD patients.
Author Contributions
S.K. formulated the idea, designed the research, researched the data, and wrote the manuscript; N.S. researched the data; A.Z. reviewed and edited the manuscript; and I.N. researched the data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and approved by the Carmel Medical Center Institutional Review Board (IRB), approval code 0136-17-CMC dated 3 January 2018.
Informed Consent Statement
Since this is a retrospective study that involved no interaction or intervention with patients, informed consent was waived, in accordance with Israeli Ministry of Health regulations.
Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Conflicts of Interest
The authors report no conflicts of interest regarding the contents of this manuscript.
References
- Belligund, P.; Attaway, A.; Lopez, R.; Damania, D.; Hatipoğlu, U.; Zein, J. Diabetes associated with higher health care utilization and poor outcomes after COPD-related hospitalizations. Am. J. Manag. Care 2022, 28, e325–e332. [Google Scholar] [PubMed]
- Kiani, F.Z.; Ahmadi, A. Prevalence of different comorbidities in chronic obstructive pulmonary disease among Shahrekord PERSIAN cohort study in southwest Iran. Sci. Rep. 2021, 11, 1548. [Google Scholar] [CrossRef] [PubMed]
- Ho, T.-W.; Huang, C.-T.; Ruan, S.-Y.; Tsai, Y.-J.; Lai, F.; Yu, C.-J. Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality. PLoS ONE 2017, 12, e0175794. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.T.-C.; Mao, I.-C.; Lin, C.-H.; Lin, S.-H.; Hsieh, M.-C. Chronic obstructive pulmonary disease: A risk factor for type 2 diabetes: A nationwide population-based study. Eur. J. Clin. Investig. 2013, 43, 1113–1119. [Google Scholar] [CrossRef]
- Peng, Y.; Zhong, G.-C.; Wang, L.; Guan, L.; Wang, A.; Hu, K.; Shen, J. Chronic obstructive pulmonary disease, lung function and risk of type 2 diabetes: A systematic review and meta-analysis of cohort studies. BMC Pulm. Med. 2020, 20, 137. [Google Scholar] [CrossRef]
- Mirrakhimov, A.E. Chronic obstructive pulmonary disease and glucose metabolism: A bitter sweet symphony. Cardiovasc. Diabetol. 2012, 11, 132. [Google Scholar] [CrossRef]
- Fabbri, L.M.; Rabe, K.F. From COPD to chronic systemic inflammatory syndrome? Lancet 2007, 370, 797–799. [Google Scholar] [CrossRef]
- Zhu, J.; Zhao, H.; Chen, D.; Tse, L.A.; Kinra, S.; Li, Y. Genetic correlation and bidirectional causal association between type 2 diabetes and pulmonary function. Front. Endocrinol. 2021, 12, 777487. [Google Scholar] [CrossRef]
- Saeed, M.I.; Eklöf, J.; Achir, I.; Sivapalan, P.; Meteran, H.; Løkke, A.; Biering-Sørensen, T.; Knop, F.K.; Jensen, J.S. Use of inhaled corticosteroids and the risk of developing type 2 diabetes in patients with chronic obstructive pulmonary disease. Diabetes Obes. Metab. 2020, 22, 1348–1356. [Google Scholar] [CrossRef]
- Price, D.B.; Russell, R.; Mares, R.; Burden, A.; Skinner, D.; Mikkelsen, H.; Ding, C.; Brice, R.; Chavannes, N.H.; Kocks, J.W.H.; et al. Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study. PLoS ONE 2016, 11, e0162903. [Google Scholar] [CrossRef]
- van den Borst, B.; Gosker, H.R.; Zeegers, M.P.; Schols AMWJ. Pulmonary function in diabetes: A metaanalysis. Chest 2010, 138, 393–406. [Google Scholar] [CrossRef] [PubMed]
- Klein, O.L.; Aviles-Santa, L.; Cai, J.; Collard, H.R.; Kanaya, A.M.; Kaplan, R.C.; Kinney, G.L.; Mendes, E.; Smith, L.; Talavera, G.; et al. Hispanics/latinos with type 2 diabetes have functional and symptomatic pulmonary impairment mirroring kidney microangiopathy: Findings from the hispanic community health study/study of latinos (HCHS/SOL). Diabetes Care 2016, 39, 2051–2057. [Google Scholar] [CrossRef] [PubMed]
- Su, J.; Li, M.; Wan, X.; Yu, H.; Wan, Y.; Hang, D.; Lu, Y.; Tao, R.; Wu, M.; Zhou, J.; et al. Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study. Diabetes Obes. Metab. 2023, 25, 2575–2585. [Google Scholar] [CrossRef]
- Gläser, S.; Krüger, S.; Merkel, M.; Bramlage, P.; Herth, F.J.F. Chronic obstructive pulmonary disease and diabetes mellitus: A systematic review of the literature. Respiration 2015, 89, 253–264. [Google Scholar] [CrossRef]
- Castañ-Abad, M.T.; Montserrat-Capdevila, J.; Godoy, P.; Marsal, J.R.; Ortega, M.; Alsedà, M.; Barbé, F. Diabetes as a risk factor for severe exacerbation and death in patients with COPD: A prospective cohort study. Eur. J. Public Health 2020, 30, 822–827. [Google Scholar] [CrossRef]
- Lin, L.; Shi, J.; Kang, J.; Wang, Q. Analysis of prevalence and prognosis of type 2 diabetes mellitus in patients with acute exacerbation of COPD. BMC Pulm. Med. 2021, 21, 7. [Google Scholar] [CrossRef]
- Raslan, A.S.; Quint, J.K.; Cook, S. All-Cause, Cardiovascular and Respiratory Mortality in People with Type 2 Diabetes and Chronic Obstructive Pulmonary Disease (COPD) in England: A Cohort Study Using the Clinical Practice Research Datalink (CPRD). Int. J. Chron Obstruct. Pulmon Dis. 2023, 18, 1207–1218. [Google Scholar] [CrossRef]
- Roversi, S.; Fabbri, L.M.; Sin, D.D.; Hawkins, N.M.; Agustí, A. Chronic obstructive pulmonary disease and cardiac diseases. An urgent need for integrated care. Am. J. Respir. Crit. Care Med. 2016, 194, 1319–1336. [Google Scholar] [CrossRef]
- Trinkmann, F.; Saur, J.; Borggrefe, M.; Akin, I. Cardiovascular Comorbidities in Chronic Obstructive Pulmonary Disease (COPD)-Current Considerations for Clinical Practice. J. Clin. Med. 2019, 8, 69. [Google Scholar] [CrossRef]
- Mannino, D.M.; Thorn, D.; Swensen, A.; Holguin, F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur. Respir. J. 2008, 32, 962–969. [Google Scholar] [CrossRef]
- Zewari, S.; Hadi, L.; van den Elshout, F.; Dekhuijzen, R.; Heijdra, Y.; Vos, P. Obesity in COPD: Comorbidities with Practical Consequences? COPD 2018, 15, 464–471. [Google Scholar] [CrossRef] [PubMed]
- Crisafulli, E.; Torres, A.; Huerta, A.; Méndez, R.; Guerrero, M.; Martinez, R.; Liapikou, A.; Soler, N.; Sethi, S.; Menéndez, R. C-Reactive Protein at Discharge, Diabetes Mellitus and ≥1 Hospitalization During Previous Year Predict Early Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. COPD 2015, 12, 306–314. [Google Scholar] [CrossRef] [PubMed]
- Almagro, P.; Cabrera, F.J.; Diez, J.; Boixeda, R.; Ortiz, M.B.A.; Murio, C.; Soriano, J.B. Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD: The EPOC en Servicios de medicina interna (ESMI) study. Chest 2012, 142, 1126–1133. [Google Scholar] [CrossRef] [PubMed]
- McGhan, R.; Radcliff, T.; Fish, R.; Sutherland, E.R.; Welsh, C.; Make, B. Predictors of rehospitalization and death after a severe exacerbation of COPD. Chest 2007, 132, 1748–1755. [Google Scholar] [CrossRef]
- Baker, C.L.; Zou, K.H.; Su, J. Risk assessment of readmissions following an initial COPD-related hospitalization. Int. J. Chron. Obs. Pulmon Dis. 2013, 8, 551–559. [Google Scholar]
- Roberts, M.H.; Clerisme-Beaty, E.; Kozma, C.M.; Paris, A.; Slaton, T.; Mapel, D.W. A retrospective analysis to identify predictors of COPD-related rehospitalization. BMC Pulm. Med. 2016, 16, 68. [Google Scholar] [CrossRef]
- Koskela, H.O.; Salonen, P.H.; Romppanen, J.; Niskanen, L. A history of diabetes but not hyperglycaemia during exacerbation of obstructive lung disease has impact on long-term mortality: A prospective, observational cohort study. BMJ Open 2015, 5, e006794. [Google Scholar] [CrossRef]
- Maan, H.B.; Meo, S.A.; Al Rouq, F.; Meo, I.M.U.; Gacuan, M.E.; Alkhalifah, J.M. Effect of glycated hemoglobin (hba1c) and duration of disease on lung functions in type 2 diabetic patients. Int. J. Environ. Res. Public Health 2021, 18, 6970. [Google Scholar] [CrossRef]
- Yeh, H.C.; Punjabi, N.M.; Wang, N.Y.; Pankow, J.S.; Duncan, B.B.; Cox, C.E.; Selvin, E.; Brancati, F.L. Cross-sectional and prospective study of lung function in adults with type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care 2008, 31, 741–746. [Google Scholar] [CrossRef]
- Paul, S.; Ali, A.; Katare, R. Molecular complexities underlying the vascular complications of diabetes mellitus—A comprehensive review. J. Diabetes Complicat. 2020, 34, 107613. [Google Scholar] [CrossRef]
- Khan, A.W.; Jandeleit-Dahm, K.A.M. Atherosclerosis in diabetes mellitus: Novel mechanisms and mechanism-based therapeutic approaches. Nat. Rev. Cardiol. 2025, 22, 482–496. [Google Scholar] [CrossRef] [PubMed]
- Krentz, A.J.; Clough, G.; Byrne, C.D. Interactions between microvascular and macrovascular disease in diabetes: Pathophysiology and therapeutic implications. Diabetes Obes. Metab. 2007, 9, 781–791. [Google Scholar] [CrossRef] [PubMed]
- Jagadapillai, R.; Rane, M.J.; Lin, X.; Roberts, A.M.; Hoyle, G.W.; Cai, L.; Gozal, E. Diabetic microvascular disease and pulmonary fibrosis: The contribution of platelets and systemic inflammation. Int. J. Mol. Sci. 2016, 17, 1853. [Google Scholar] [CrossRef]
- Di Raimondo, D.; Pirera, E.; Pintus, C.; De Rosa, R.; Profita, M.; Musiari, G.; Siscaro, G.; Tuttolomondo, A. The role of the cumulative illness rating scale (CIRS) in estimating the impact of comorbidities on chronic obstructive pulmonary disease (COPD) outcomes: A pilot study of the MACH (multidimensional approach for COPD and high complexity) study. J. Pers. Med. 2023, 13, 1674. [Google Scholar] [CrossRef]
- Garvey, C.; Criner, G.J. Impact of comorbidities on the treatment of chronic obstructive pulmonary disease. Am. J. Med. 2018, 131, 23–29. [Google Scholar] [CrossRef]
Figure 1.
Six-month readmission/mortality Kaplan–Meier survival function curves for controlled vs. uncontrolled diabetes. Log rank: p = 0.009.
Figure 1.
Six-month readmission/mortality Kaplan–Meier survival function curves for controlled vs. uncontrolled diabetes. Log rank: p = 0.009.
Table 1.
Baseline demographics and clinical characteristics of type 2 diabetes patients admitted due to COPD exacerbation. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
Table 1.
Baseline demographics and clinical characteristics of type 2 diabetes patients admitted due to COPD exacerbation. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
| Total N = 426 | HbA1c < 7.5% N = 247 (58%) | HbA1c ≥ 7.5% N = 179 (42%) | p-Value | |
|---|---|---|---|---|
| Age (years) | 73.2 ± 10.2 | 74.0 ± 9.5 | 72.2 ± 11.1 | 0.06 |
| Male | 280 (65.7) | 159 (64.4) | 121 (67.6) | 0.489 |
| Hypertension | 393 (92.3) | 223 (90.3) | 170 (95.0) | 0.074 |
| Ischemic Heart Disease | 275 (64.6) | 138 (55.9) | 137 (76.5) | <0.0001 |
| Heart Failure | 239 (56.1) | 123 (49.8) | 116 (64.8) | 0.002 |
| Inhaled Corticosteroids | 244 (57.3) | 137(55.5) | 107 (59.8) | 0.375 |
| LABA/LAMA inhaler | 237 (55.6) | 136 (55.1) | 101 (56.4) | 0.78 |
| Home oxygen therapy | 182 (42.8) | 107 (43.3) | 75 (42.1) | 0.873 |
| Mechanical ventilation | 117 (27.5) | 68 (27.5) | 49 (27.4) | 0.972 |
| Days of hospital stay: mean ± std. | 7.0 ± 4.1 | 6.7 ± 3.8 | 7.3 ± 4.6 | 0.283 |
Table 2.
Univariate and multivariate analyses (for variables with p < 0.1 on univariate analysis) of the composite 6-month rehospitalization/mortality. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
Table 2.
Univariate and multivariate analyses (for variables with p < 0.1 on univariate analysis) of the composite 6-month rehospitalization/mortality. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
| Univariate Analysis | ||||
|---|---|---|---|---|
| 6-Month Rehospitalization/Mortality | Adjusted HR95%CI | p-Value | ||
| No | Yes | |||
| N = 296 | N = 130 | |||
| HbA1c% | ||||
| <7% | 183 (61.8) | 113 (38.2) | ||
| ≥7.5% | 64 (49.2) | 66 (50.8) | 1.60 (1.11–2.3) | 0.01 |
| Age | 72.6 ± 10.4 | 75.0 ± 9.7 | 1.02 (1.00–1.04) | 0.04 |
| Home oxygen therapy | ||||
| No | 187 (63.1) | 57 (43.9) | ||
| Yes | 109 (36.9) | 73 (56.2) | 1.98 (1.37–2.88) | 0.0003 |
| Gender | ||||
| Male | 191 (64.5) | 89 (68.5) | ||
| Female | 105 (35.5) | 41 (31.5) | 0.86 (0.58–1.28) | 0.464 |
| Inhaled Corticosteroids | ||||
| No | 159 (45.0) | 23 (31.5) | ||
| Yes | 194 (55.0) | 50 (68.5) | 1.47 (0.87–2.5) | 0.147 |
| LABA/LAMA | ||||
| No | 140 (47.3) | 49 (37.7) | ||
| Yes | 156 (52.7) | 81 (62.3) | 1.35 (0.94–1.96) | 0.109 |
| Hypertension | ||||
| No | 20 (6.8) | 13 (10.0) | ||
| Yes | 276 (93.2) | 117 (90.0) | 0.71 (0.39–1.3) | 0.271 |
| Ischemic Heart Disease | ||||
| No | 106 (35.8) | 45 (34.6) | ||
| yes | 190 (64.2) | 85 (65.4) | 1.05 (0.71–1.54) | 0.802 |
| Heart Failure | ||||
| No | 132 (44.6) | 55 (42.3) | ||
| Yes | 164 (55.4) | 75 (57.7) | 1.11 (0.77–1.61) | 0.562 |
| Multivariate analysis | ||||
| Adjusted HR | p-value | |||
| HbA1c ≥ 7.5% | 1.82 (1.24–2.67) | 0.002 | ||
| Age | 1.02 (1.00–1.04) | 0.036 | ||
| Home Oxygen Therapy | 2.22 (1.53–3.22) | <0.0001 | ||
Table 3.
Univariate and multivariate analyses (for variables with p < 0.1 on univariate analysis): 6-month rehospitalization. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
Table 3.
Univariate and multivariate analyses (for variables with p < 0.1 on univariate analysis): 6-month rehospitalization. LABA—long-acting beta agonists; LAMA—long-acting muscarinic agonists.
| Univariate Analysis | 6-Month Rehospitalization | Adj HR95%CI | p-Value | |
|---|---|---|---|---|
| No | Yes | |||
| N = 353 | N = 73 | |||
| HbA1c% | ||||
| <7.5 | 214 (60.6) | 33 (45.2) | ||
| ≥7.5% | 139 (39.4) | 40 (54.8) | 1.94 (1.16–3.23) | 0.011 |
| Age | 73.6 ± 10.3 | 71.4 ± 9.4 | 0.99 (0.96–1.01) | 0.353 |
| Home oxygen therapy | ||||
| No | 216 (61.4) | 27 (37) | ||
| Yes | 136 (38.6) | 46 (63.0) | 2.23 (1.33–3.75) | 0.003 |
| Gender | ||||
| Male | 231 (65.4) | 49 (67.1) | ||
| Female | 122 (34.6) | 24 (32.9) | 0.99 (0.57–1.74) | 0.997 |
| Inhaled Corticosteroids | ||||
| No | 159 (45.0) | 23 (31.5) | ||
| Yes | 194 (55.0) | 50 (68.5) | 1.47 (0.87–2.5) | 0.147 |
| LABA/LAMA | ||||
| No | 165 (46.7) | 24 (32.9) | ||
| Yes | 188 (53.3) | 49 (67.1) | 1.58 (0.94–2.66) | 0.087 |
| Hypertension | ||||
| No | 25 (7.1) | 8 (11.0) | ||
| Yes | 328 (92.9) | 65 (89.0) | 0.66 (0.29–1.49) | 0.319 |
| Ischemic Heart Disease | ||||
| No | 124 (35.1) | 27 (37.0) | ||
| Yes | 229 (64.9) | 46 (63.0) | 0.98 (0.57–1.68) | 0.946 |
| Heart Failure | ||||
| No | 149 (42.2) | 38 (52.1) | ||
| Yes | 204 (57.8) | 35 (47.9) | 0.79 (0.48–1.31) | 0.366 |
| Multivariate analysis | ||||
| Adjusted HR | p-value | |||
| HbA1c ≥ 7.5 | 1.98 (1.19–3.27) | 0.008 | ||
| LABA/LAMA Inhaler | 1.40 (0.82–2.38) | 0.219 | ||
| Home oxygen Therapy | 1.84 (2.2–3.2) | 0.028 | ||
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Kassem, S.; Zaina, A.; Stein, N.; Naoum, I. Diabetes Control and Clinical Outcomes in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation. Diabetology 2025, 6, 66. https://doi.org/10.3390/diabetology6070066
AMA Style
Kassem S, Zaina A, Stein N, Naoum I. Diabetes Control and Clinical Outcomes in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation. Diabetology. 2025; 6(7):66. https://doi.org/10.3390/diabetology6070066
Chicago/Turabian StyleKassem, Sameer, Adnan Zaina, Nili Stein, and Ibrahim Naoum. 2025. "Diabetes Control and Clinical Outcomes in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation" Diabetology 6, no. 7: 66. https://doi.org/10.3390/diabetology6070066
APA StyleKassem, S., Zaina, A., Stein, N., & Naoum, I. (2025). Diabetes Control and Clinical Outcomes in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation. Diabetology, 6(7), 66. https://doi.org/10.3390/diabetology6070066
