COPD Risk With Diabetes And Pre-Diabetes
A new trail-blazing study links diabetes, pre-diabetic states, and an extended duration of diabetes to an increased risk of chronic obstructive pulmonary disease development. This article will explore this ground-breaking research and its findings.
Background of the Study
Diabetes and chronic obstructive pulmonary diseases (COPD) are among the most prevalent chronic illnesses globally [2] [3]. Recent Estimates show that over 200 million individuals live with COPD – a primary and long-term respiratory disorder characterized by airflow limitation and persistent pulmonary symptoms [2]. Likewise, experts estimate that over 400 million individuals have diabetes worldwide [3]. Furthermore, studies have shown that about ten (10) percent of people living with diabetes globally also have chronic obstructive pulmonary disease (COPD) [4]. Considering the significant number of people affected by these conditions independently, this implies that a sizeable population lives with both illnesses concurrently.
Evidence from several cross-sectional studies indicating people with COPD are more likely to be diabetic than the overall population [5] [6]. Similar studies also show that the clinical outcomes of patients with COPD who have diabetes are worse [7]. These patients have more extended hospital stays and more significant direct hospitalization expenses.
Furthermore, clinical research has demonstrated that hyperglycemia worsens the prognosis and progression of COPD. Additionally, cohort research using the United Kingdom Clinical Practice Research Datalink found that patients who took antidiabetic medicines had a much lower probability of experiencing a severe exacerbation of their COPD [8].
While lots of research has been done on both conditions individually and collectively, there is a shortage of studies linking diabetes, other hyperglycaemic states like pre-diabetes, and the length of diabetes to a raised risk of COPD development. Also, the findings of retrospective studies on the subject matter are conflicting. For instance, a survey by American experts suggests that persons with diabetes are more predisposed to COPD [6]. In contrast, an English retrospective case-control research indicated decreased COPD incidence in diabetic patients [9].
The study aimed to provide more clarity and investigate if diabetes, the duration of diabetes, and pre-diabetes could predispose patients to chronic obstructive pulmonary diseases.
The Study Method
This prospective study employed data from the UK Biobank — a huge biomedical database and research tool containing comprehensive genetic and health data from 500,000 UK participants. During the baseline survey, trained staff interviewed each participant face-to-face using a standardized e-questionnaire that included sociodemographic characteristics, behavioral factors, lifestyle, physical health, and family histories. Trained technicians performed physical examinations and obtained blood samples for biochemical testing.
Over 450,000 individuals were included in this study. Patients diagnosed with COPD, those with obstructive airway symptoms, and those with sub-optimal lung function tests before the study were excluded.
The participants were categorized into three groups (diabetes, pre-diabetes, and no-diabetes) based on their diabetes status ascertained by a diagnosis by a physician, self-reported symptoms, and HbA1c level. Similarly, the participants were also divided into four groups of diabetes duration (less than a year, between a year and three years, between three and seven years, and seven years and above). The primary endpoint for the study was the new instances of COPD diagnosed among the participants, while the secondary endpoints were deaths from COPD and other causes [1]. Cases of incident COPD and fatalities from the disease were found by data matching with national hospital and death registries.
The Analysis
The baseline traits of the participants were summed up based on whether or not the person had diabetes and how long they had had it. Assessing the COPD risk of the participants, person-years were counted from the initial date of COPD diagnosis, death, loss to follow-up, or the conclusion of the study, whichever came first.
The hazard ratios (HRs) for COPD risk linked with diabetes status and duration were estimated using the Cox proportional hazards regression models, and the confidence intervals (CIs) were set at 95%. Furthermore, for parameters with missing data, a missing indicator approach was utilized for categorical variables, whereas median values were imputed for continuous variables. The researchers also investigated the dose-response correlation between diabetes duration and COPD risk using restricted cubic spline regression with four knots (a p-value of less than 0.05 was considered nonlinear). The age, gender, socioeconomic status, body mass index, smoking history, exercise routine, and forced expiratory volume in one second (FEV1/FVC) were used to conduct separate stratified analyses. To examine the potential effect modification of pre-diabetes, diabetes, and duration of diabetes with stratification variables, a likelihood ratio test was used to correlate models with and without interaction terms. Also, three sensitivity analyses were performed by excluding participants with incident COPD during the first two years of follow-up, those with asthma at baseline, and those with overall poor self-reported health.
For survival analysis, the researchers determined the overall and COPD-specific survival time from the initial diagnosis of COPD until mortality or the end of follow-up. The hazard ratios and confidence intervals for overall and COPD-specific survival were determined using multivariate Cox regression analysis. Kaplan-Meier methods with log-rank tests were also used to create broad survival curves. SAS 9.4 was used for all the statistical analyses. Statistical significance was assumed at a two-tailed p-value of less than 0.05.
Study Findings
This study included 452,680 participants from a UK biobank database. Most participants were women (54.8%), and their average age was about fifty-six years (56). Over 50000 (11.8%) of the study’s participants had pre-diabetes, while just six percent had diabetes. Concerning diabetes duration, the majority of the participants with diabetes (53.5%) had been living with the condition for over three years.
A total of 12,595 instances of COPD were detected after a follow-up period of roughly 12 years for each participant. In COPD patients, there were 3167 fatalities (259 of which were COPD-related) over the median follow-up of 3.8 years following COPD diagnosis.
Analysis of the study’s data revealed the following findings:
- Compared to the control group, participants with pre-diabetes and diabetes had an 18% and 35% increased risk of COPD, respectively.
- Prolonged diabetes duration was associated with a raised COPD risk as more participants who had been living with diabetes for more than a year developed COPD compared to those who had diabetes for less than a year.
- Participants who had pre-diabetes or diabetes and are smokers are at a higher risk of COPD than those who dont smoke.
- Stratified analysis of the data revealed that the associations between pre-diabetes and diabetes and COPD were more robust among males, smokers, participants younger than 60 years, those with FEV1/FVC ratios below the median, and those with a lower Townsend Deprivation Index.
- The survival analysis revealed that pre-diabetes and diabetes were linked to a lower overall survival rate. Patients with COPD with pre-diabetes or diabetes were 9% and 21% more likely to die from any cause than those in the control group.
Discussion
This prospective study of 452,680 people in the UK found that having pre-diabetes, diabetes, or having had diabetes for a longer time was linked to a higher risk of COPD [1]. In addition, among smokers, the associations between pre-diabetes and diabetes and COPD risk appeared stronger than among never-smokers. In addition, the study revealed that COPD patients with pre-diabetes, diabetes, or a prolonged duration of diabetes had a reduced overall survival rate. These results suggest that the diagnosis and course of diabetes may have a role in the initiation and progression of COPD [1].
Several other research works corroborate the findings of this fantastic study. For instance, a recent observational study indicates that Patients with diabetes are likely to have worse lung function than those without diabetes [10]. Another cross-sectional study of 53,418 people in the US showed that those with diabetes were more likely to have COPD than those without diabetes [11].
Importantly, this study suggests that behaviors like smoking could significantly affect the risk of COPD development. It implies that lifestyle modifications like smoking cessation could substantially reduce a diabetic patient’s risk of COPD.
The exact mechanism by which diabetes causes COPD is still in debate. More research can help delineate its precise pathophysiology. Furthermore, experts have suggested that damage caused by hyperglycemia starts early at the pre-diabetic stage (a prodromal phase that’s reversible and milder than diabetic disease). Clinical evidence shows that 31% to 40% of people with COPD seeking medical care have pre-diabetes [12]. This finding supports the hypothesis of a continuous increase in COPD risk from normoglycaemia to diabetes.
Concerning the prognosis of COPD among diabetic patients, the findings of this study are consistent with those of previous research, indicating a negative association between diabetes and COPD patient survival time.
Limitations of the Study
This study has some limitations that must be taken into account. They include;
- The study’s observational design may lead to reverse causality or residual confounding.
- The 2-hour post-prandial blood glucose level was not measured. This test identifies incident diabetes more accurately than HbA1c. Consequently, misclassification bias may exist due to undiagnosed diabetes in the reference group.
- The study evaluated diabetes status based on baseline data but did not consider new diabetes diagnoses during the follow-up period.
- The temporal lag between the onset and the diagnosis of COPD was not considered. The duration of diabetes was computed in part using self-reported age at diagnosis, which may be inaccurate.
- The self-reported data from the baseline questionnaire may be subject to recall bias.
Conclusion
This study suggests that diabetes, pre-diabetes, and a longer duration of diabetes are associated with an increased risk of COPD and a lower survival rate from COPD. However, more research is needed to understand the mechanisms at play better and to identify the best ways to keep blood glucose levels under control to lower the risk of chronic obstructive pulmonary disease (COPD) in the general population.
References
- Su, J., Li, M., Wan, X., Yu, H., Wan, Y., Hang, D., Lu, Y., Tao, R., Wu, M., Zhou, J., & Fan, X. (2023). Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study. Diabetes, Obesity & Metabolism. https://doi.org/10.1111/dom.15142
- Safiri, S., Carson-Chahhoud, K., Noori, M., Nejadghaderi, S. A., Sullman, M. J. M., Ahmadian Heris, J., Ansarin, K., Mansournia, M. A., Collins, G. S., Kolahi, A.-A., & Kaufman, J. S. (2022). Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. BMJ (Clinical Research Ed.), 378, e069679. https://doi.org/10.1136/bmj-2021-069679
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- Gläser, S., Krüger, S., Merkel, M., Bramlage, P., & Herth, F. J. (2015). Chronic obstructive pulmonary disease and diabetes mellitus: a systematic review of the literature. Respiration; international review of thoracic diseases, 89(3), 253–264. https://doi.org/10.1159/000369863
- Lin, L., Shi, J., Kang, J., & Wang, Q. (2021). Analysis of prevalence and prognosis of type 2 diabetes mellitus in patients with acute exacerbation of COPD. BMC pulmonary medicine, 21(1), 7. https://doi.org/10.1186/s12890-020-01371-9
- Ehrlich, S. F., Quesenberry, C. P., Jr, Van Den Eeden, S. K., Shan, J., & Ferrara, A. (2010). Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes care, 33(1), 55–60. https://doi.org/10.2337/dc09-0880
- Ho, T. W., Huang, C. T., Ruan, S. Y., Tsai, Y. J., Lai, F., & Yu, C. J. (2017). Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality. PloS one, 12(4), e0175794. https://doi.org/10.1371/journal.pone.0175794
- Pradhan, R., Lu, S., Yin, H., Yu, O. H. Y., Ernst, P., Suissa, S., & Azoulay, L. (2022). Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study. BMJ (Clinical research ed.), 379, e071380. https://doi.org/10.1136/bmj-2022-071380
- Rayner, L. H., McGovern, A. P., Sherlock, J., Gatenby, P., Correa, A., Creagh-Brown, B., & de Lusignan, S. (2018). Type 2 diabetes: A protective factor for COPD?. Primary care diabetes, 12(5), 438–444. https://doi.org/10.1016/j.pcd.2018.05.002
- Klein, O. L., Meltzer, D., Carnethon, M., & Krishnan, J. A. (2011). Type II diabetes mellitus is associated with decreased measures of lung function in a clinical setting. Respiratory medicine, 105(7), 1095–1098. https://doi.org/10.1016/j.rmed.2011.03.010
- George, C., Ducatman, A. M., & Conway, B. N. (2018). Increased risk of respiratory diseases in adults with Type 1 and Type 2 diabetes. Diabetes research and clinical practice, 142, 46–55. https://doi.org/10.1016/j.diabres.2018.05.029
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