Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women's Health Study

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Abstract

Background

Chronic airway inflammation in asthma or chronic obstructive pulmonary disease (COPD) may be involved in the pathogenesis of type 2 diabetes; however, prospective data have been limited.

Methods

A prospective cohort of 38,570 women who were aged ≥45 years, free of cardiovascular disease and cancer at baseline, and free of diabetes at baseline and in the first 12 months were analyzed. We classified all women into three groups according to the presence and absence of self-reported asthma or COPD (including emphysema, chronic bronchitis, and bronchiectasis).

Results

During a median follow-up of 12.2 years, 2472 incident type 2 diabetes events were documented. Women who had ever reported asthma or COPD were associated with an increased diabetes risk; the multivariate RRs were 1.37 (95% CI, 1.20–1.57) for women who had asthma alone and 1.38 (95% CI, 1.14–1.67) for COPD without asthmatic symptoms. Furthermore, these associations were not significantly modified by age, smoking status, physical activity, BMI, alcohol intake, hormone replacement therapy, menopausal status or randomized treatment.

Conclusions

Asthma and COPD were individually and independently associated with an increased risk of type 2 diabetes in women, indicating that chronic airway inflammation may contribute to diabetes pathogenesis.

Introduction

Asthma and COPD are inflammatory lung disorders associated with significant morbidity and mortality worldwide [1]. Their commonly reported comorbidities include cardiovascular disease, diabetes mellitus, hypertension, osteoporosis, and other chronic medical conditions [2]. Respiratory viral and bacterial infections, tobacco smoking, and pollutants are important factors in triggering a plethora of inflammatory pathways that may mediate the relation of chronic lung diseases and their comorbid diseases [1], [2]. Although the inflammatory process in COPD is different from that in asthma in terms of inflammatory cells, mediators, and inflammatory response to therapy [3], there is growing evidence to show a role of several common inflammatory signaling pathways in the pathogenesis of both asthma [4] and COPD [5]. Low-grade inflammation as reflected by elevated levels of many proinflammatory biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and adhesion molecules has been recognized as a major contributor to the development of type 2 diabetes [6], [7]. It thus seems reasonable to speculate that elevated circulating levels of certain inflammatory cytokines caused by chronic airway inflammation may also contribute to the development of insulin resistance in the liver, skeletal muscle, and vascular endothelium, ultimately leading to the clinical expression of type 2 diabetes.

In epidemiologic studies, several cross-sectional studies have suggested that lung function impairment was associated with high prevalence of the metabolic syndrome [8] and type 2 diabetes, even after adjusting for adiposity [2]. Several prospective studies have shown inverse associations between lung functions and risk for developing insulin resistance or type 2 diabetes in nondiabetic individuals from diverse populations [9], [10], [11]. One recent prospective cohort study from the Nurses’ Health Study reported increased risk of type 2 diabetes associated with patients with COPD but not among asthma patients [12]. Although the differences in the diabetes risk between patients with COPD and those with asthma may reflect the different underlying inflammatory processes in asthma and COPD, no other independent studies have confirmed this relationship.

We therefore prospectively examined the association of asthma and COPD with risk of type 2 diabetes in a large cohort of women with over 12 years of follow-up. In addition, we investigated whether the associations would vary for the presence of asthma and/or COPD when examined separately and whether they would differ according to levels of potential factors, including age, BMI, smoking status, physical activity, alcohol intake, postmenopausal hormone use, and menopausal status.

Section snippets

Study population

The Women's Health Study (WHS) was a randomized, double-blind, placebo-controlled trial designed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease (CVD) and cancer [13]. As described previously, participants provided detailed information on behavioral, lifestyle, and demographic risk factors at baseline [14]. In total, 39,876 female health professionals aged ≥45 years who were free of coronary heart disease (CHD),

Characteristics of women with and without chronic lung diseases

The prevalence of patients with COPD or asthma was 16.4% (n = 6322) among all participants. There were 1808 women with COPD without asthmatic component, among whom, 32.7% were never smokers, 32.6% were past smokers, and 35.7% were current smokers. The prevalence of patients with asthma alone (n = 3368) was 8.73%, among whom, 52.6% were never smokers, 38.9% were past smokers, and 8.5% were current smokers.

Overall, women with self-reported asthma or COPD were older and heavier, were less likely to

Discussion

In this large prospective study of middle-aged and older US women followed over 12 years, we found that patients with pre-existing asthma and/or COPD had a higher risk of developing subsequent type 2 diabetes than those without. The positive associations between these chronic lung diseases and type 2 diabetes were independent of cigarette smoking and other diabetes risk factors and also persisted after excluding all COPD cases with asthmatic symptoms. We further investigated any potential

Conflict of interest

There are no conflicts of interest.

Acknowledgements

We are indebted to the 39,876 dedicated and committed participants of the Women's Health Study. We also acknowledge the contributions of the entire staff of the Women's Health Study.

The Women's Health Study was supported by research grants DK066401, HL 043851, HL 080467, and CA 047988 from the National Institutes of Health, Bethesda, MD. Dr. Song is supported by a grant (K01-DK078846) from the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institutes of

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