Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank

AIMS To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.

[1]  Minzhou Zhang,et al.  Relationship of Glycated Hemoglobin A1c with All-Cause and Cardiovascular Mortality among Patients with Hypertension , 2023, Journal of clinical medicine.

[2]  Jinhe Cui,et al.  Elevated Blood Glucose is Associated with Severe Exacerbation of Chronic Obstructive Pulmonary Disease , 2022, International journal of chronic obstructive pulmonary disease.

[3]  A. Jafarinezhad,et al.  The relationship between glycated hemoglobin A1c levels and exacerbation status in the patients with chronic obstructive pulmonary disease , 2022, BMC Research Notes.

[4]  Donghua Xie,et al.  Association between secondhand smoke exposure in pregnant women and their socioeconomic status and its interaction with age: a cross-sectional study , 2022, BMC Pregnancy and Childbirth.

[5]  C. McCarthy,et al.  Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD? , 2022, Medicina.

[6]  G. Collins,et al.  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 , 2022, BMJ.

[7]  W. Rathmann,et al.  Socioeconomic Factors Associated With Glycemic Measurement and Poor HbA1c Control in People With Type 2 Diabetes: The Global DISCOVER Study , 2022, Frontiers in Endocrinology.

[8]  M. Hashemipour,et al.  Factors related to glycemic control in children and adolescents with type 1 diabetes mellitus in Isfahan, Iran , 2021, Journal of Diabetes & Metabolic Disorders.

[9]  W. Rathmann,et al.  Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium , 2021, Cardiovascular Diabetology.

[10]  S. Meo,et al.  Effect of Glycated Hemoglobin (HbA1c) and Duration of Disease on Lung Functions in Type 2 Diabetic Patients , 2021, International journal of environmental research and public health.

[11]  S. Loukides,et al.  Glycated Hemoglobin (HbA1c) as a Predictor of Outcomes during Acute Exacerbations of Chronic Obstructive Pulmonary Disease , 2021, COPD.

[12]  D. Telesca,et al.  Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999-2015. , 2020, International journal of epidemiology.

[13]  R. Simó,et al.  Non-linear association between diabetes mellitus and pulmonary function: a population-based study , 2020, Respiratory Research.

[14]  A. Eid,et al.  Role of diabetes in lung injury from acute exposure to electronic cigarette, heated tobacco product, and combustible cigarette aerosols , 2020 .

[15]  M. Redondo,et al.  Relationship between glycemic control and chronic obstructive pulmonary disease in patients with type 2 diabetes: A nested case-control study. , 2020, Primary care diabetes.

[16]  P. Godoy,et al.  Diabetes as a risk factor for severe exacerbation and death in patients with COPD: a prospective cohort study. , 2020, European journal of public health.

[17]  D. Mikhailidis,et al.  Diabetes Mellitus and Chronic Obstructive Pulmonary Disease: An Overview , 2019, Experimental and Clinical Endocrinology & Diabetes.

[18]  Xianbo Wu,et al.  Glycated Hemoglobin and All-Cause and Cause-Specific Mortality Among Adults With and Without Diabetes. , 2019, The Journal of clinical endocrinology and metabolism.

[19]  M. Bogdan,et al.  Predictors of Long-term Mortality after Hospitalization for Severe COPD Exacerbation. , 2019, Maedica.

[20]  Te-Wei Ho,et al.  Metformin use mitigates the adverse prognostic effect of diabetes mellitus in chronic obstructive pulmonary disease , 2019, Respiratory Research.

[21]  Nan Wu,et al.  Insulin in high concentration recede cigarette smoke extract induced cellular senescence of airway epithelial cell through autophagy pathway. , 2019, Biochemical and biophysical research communications.

[22]  Y. Ohno,et al.  The association between glycemic control and lung function impairment in individuals with diabetes: the Saku study , 2018, Diabetology International.

[23]  B. Li,et al.  Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1. , 2017, Molecular medicine reports.

[24]  Chia-Ing Li,et al.  Visit-to-visit glycemic variability is a strong predictor of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus: Competing risk analysis using a national cohort from the Taiwan diabetes study , 2017, PloS one.

[25]  Te-Wei Ho,et al.  Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality , 2017, PloS one.

[26]  E. Huang,et al.  Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988–2011) , 2017, Diabetes Care.

[27]  E. Horikawa,et al.  Relationship between pulmonary function and elevated glycated hemoglobin levels in health checkups: A cross-sectional observational study in Japanese participants , 2017, Journal of epidemiology.

[28]  S. Davis,et al.  Understanding the impact of hypoglycemia on the cardiovascular system , 2017, Expert review of endocrinology & metabolism.

[29]  P. Cullinan,et al.  Occupations associated with COPD risk in the large population-based UK Biobank cohort study , 2016, Occupational and Environmental Medicine.

[30]  A. Linneberg,et al.  Hyperinsulinemia adversely affects lung structure and function. , 2016, American journal of physiology. Lung cellular and molecular physiology.

[31]  G. Brinkworth,et al.  Glycemic Variability: Assessing Glycemia Differently and the Implications for Dietary Management of Diabetes. , 2015, Annual review of nutrition.

[32]  F. Herth,et al.  Chronic Obstructive Pulmonary Disease and Diabetes Mellitus: A Systematic Review of the Literature , 2015, Respiration.

[33]  S. Badarny,et al.  The impact of corticosteroid treatment on hemoglobin A1C levels among patients with type-2 diabetes with chronic obstructive pulmonary disease exacerbation. , 2014, Respiratory medicine.

[34]  J. Milanowski,et al.  Relationship between COPD and lower socioeconomic status in farmers from South-Eastern Poland (Lublin region). , 2014, Rural and remote health.

[35]  E. Regan,et al.  Pulmonary Function Reduction in Diabetes With and Without Chronic Obstructive Pulmonary Disease , 2014, Diabetes Care.

[36]  J. Meier GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus , 2012, Nature Reviews Endocrinology.

[37]  A. Amos,et al.  Smoking and socioeconomic status in England: the rise of the never smoker and the disadvantaged smoker. , 2012, Journal of public health.

[38]  E. Selvin,et al.  Low hemoglobin A(1c) in nondiabetic adults: an elevated risk state? , 2012, Diabetes care.

[39]  Yun-Chul Hong,et al.  Association between environmental tobacco smoke exposure of children and parental socioeconomic status: a cross-sectional study in Korea. , 2012, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[40]  Irina Tolstykh,et al.  Socioeconomic status, race and COPD health outcomes , 2009, Journal of Epidemiology & Community Health.

[41]  M. Porawski,et al.  Experimental diabetes mellitus: oxidative stress and changes in lung structure. , 2009, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia.

[42]  B. Frier,et al.  Vascular disease and diabetes: is hypoglycaemia an aggravating factor? , 2008, Diabetes/metabolism research and reviews.

[43]  J. Manson,et al.  HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women , 2008, Diabetologia.

[44]  T. Seemungal,et al.  Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD , 2005, Chest.

[45]  D. Lawlor,et al.  Association between self-reported childhood socioeconomic position and adult lung function: findings from the British Women’s Heart and Health Study , 2004, Thorax.

[46]  G. O'Connor,et al.  Association between glycemic state and lung function: the Framingham Heart Study. , 2003, American journal of respiratory and critical care medicine.

[47]  E. Broadfield,et al.  Prospective study of diet and decline in lung function in a general population. , 2002, American journal of respiratory and critical care medicine.

[48]  H. Schünemann,et al.  Lung function in relation to intake of carotenoids and other antioxidant vitamins in a population-based study. , 2002, American journal of epidemiology.

[49]  K. Lam,et al.  Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. , 2002, The Journal of clinical endocrinology and metabolism.

[50]  E. Ford Body mass index, diabetes, and C-reactive protein among U.S. adults. , 1999, Diabetes care.

[51]  R. Norton,et al.  Association of environmental tobacco smoke exposure with socioeconomic status in a population of 7725 New Zealanders. , 1998, Tobacco control.

[52]  Charles M Peterson,et al.  Tests of glycemia in diabetes. , 1995, Diabetes care.

[53]  Andrés Ledesma Velázquez,et al.  Glycemic disorders and their impact on lung function. Cross-sectional study. , 2018, Medicina clinica.

[54]  Xiaomin Wei,et al.  A meta-analysis of passive smoking and risk of developing Type 2 Diabetes Mellitus. , 2015, Diabetes research and clinical practice.

[55]  Yichong Li,et al.  Prevalence of COPD and its association with socioeconomic status in China: Findings from China Chronic Disease Risk Factor Surveillance 2007 , 2011 .