Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • Log out
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Pathophysiology/Complications

Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study

  1. Liliana Gutiérrez-Carrasquilla1,
  2. Enric Sánchez1,
  3. Ferran Barbé2,3,
  4. Mireia Dalmases2,3,
  5. Carolina López-Cano1,
  6. Marta Hernández1,
  7. Ferran Rius1,
  8. Paola Carmona2,
  9. Cristina Hernández4,5,
  10. Rafael Simó4,5⇑ and
  11. Albert Lecube1,5⇑
  1. 1Endocrinology and Nutrition Department, Hospital Universitari Arnau de Vilanova, Obesity, Diabetes and Metabolism Research Group (ODIM), Institut de Recerca Biomèdica de Lleida (IRBLleida), and Universitat de Lleida, Lleida, Catalonia, Spain
  2. 2Respiratory Department, Hospital Universitari Arnau de Vilanova-Santa María, Translational Research in Respiratory Medicine, Institut de Recerca Biomèdica de Lleida (IRBLleida), and Universitat de Lleida, Lleida, Catalonia, Spain
  3. 3Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
  4. 4Endocrinology and Nutrition Department, Hospital Universitari Vall d’Hebron, Diabetes and Metabolism Research Unit, Vall d’Hebron Institut de Recerca (VHIR), and Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
  5. 5Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
  1. Corresponding author: Albert Lecube, alecube{at}gmail.com, or Rafael Simó, rafael.simo{at}vhir.org
Diabetes Care 2019 Apr; 42(4): 617-624. https://doi.org/10.2337/dc18-1948
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

Abstract

OBJECTIVE Type 2 diabetes exerts a deleterious effect on lung function. However, it is unknown whether an improvement in glycemic control ameliorates pulmonary function.

RESEARCH DESIGN AND METHODS Prospective interventional study with 60 patients with type 2 diabetes and forced expiratory volume in 1 s (FEV1) ≤90% of predicted. Spirometric maneuvers were evaluated at baseline and after a 3-month period in which antidiabetic therapy was intensified. Those with an HbA1c reduction of ≥0.5% were considered to be good responders (n = 35).

RESULTS Good responders exhibited a significant improvement in spirometric values between baseline and the end of the study (forced vital capacity [FVC]: 78.5 ± 12.6% vs. 83.3 ± 14.7%, P = 0.029]; FEV1: 75.6 ± 15.3% vs. 80.9 ± 15.4%, P = 0.010; and peak expiratory flow [PEF]: 80.4 ± 21.6% vs. 89.2 ± 21.0%, P = 0.007). However, no changes were observed in the group of nonresponders when the same parameters were evaluated (P = 0.586, P = 0.987, and P = 0.413, respectively). Similarly, the initial percentage of patients with a nonobstructive ventilatory defect and with an abnormal FEV1 decreased significantly only among good responders. In addition, the absolute change in HbA1c inversely correlated to increases in FEV1 (r = −0.370, P = 0.029) and PEF (r = −0.471, P = 0.004) in the responders group. Finally, stepwise multivariate regression analysis showed that the absolute change in HbA1c independently predicted increased FEV1 (R2 = 0.175) and PEF (R2 = 0.323). In contrast, the known duration of type 2 diabetes, but not the amelioration of HbA1c, was related to changes in forced expiratory flow between 25% and 75% of the FVC.

CONCLUSIONS In type 2 diabetes, spirometric measurements reflecting central airway obstruction and explosive muscle strength exhibit significant amelioration after a short improvement in glycemic control.

Introduction

The lungs are not conventionally included in the target list of organs that may be affected by type 2 diabetes. However, with its large vascularization and rich amount of collagen and elastin fibers, the lung parenchyma appears to be a potential target of chronic hyperglycemia (1–3). In fact, the same histological and physiologic disturbances that account for complications in other tissues may also be involved in the deleterious impact of type 2 diabetes on pulmonary function (3). Therefore, insulin resistance (IR), low-grade systemic inflammation, lung microangiopathy, leptin resistance, autonomic neuropathy, defects in the bronchiolar surfactant layer, and reduced muscle strength have been involved as pathogenic factors (3,4).

Several large epidemiological studies have described how adults with type 2 diabetes have lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values than the healthy population (1,5–8). Moreover, an inverse association has been observed between fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and spirometric values (5,7,8). Longitudinal studies (8,9) have also documented a faster decline of FVC and FEV1 among patients with type 2 diabetes than that observed in their counterparts without diabetes. More importantly, data from the Fremantle Diabetes Study (6) showed that for every 1% increase in the HbA1c level, an FVC decline of 4% predicted value was observed. Although lung damage and respiratory abnormalities were of moderate magnitude and even subclinical, there could be a long-term deleterious impact. In this regard, a 10% decrease in FEV1 was an independent predictor of all-cause mortality in the population with type 2 diabetes (6).

Basic research and epidemiological and clinical data also support the notion that type 2 diabetes has a deleterious effect on sleep breathing and is an independent risk factor for severe nocturnal hypoxemia (10). Moreover, our group demonstrated a significant reversibility of the increased number of nocturnal oxygen desaturation events after only 5 days of intensified glycemic treatment (11). However, it is unknown whether an improvement in glycemic control can also ameliorate lung function parameters in patients with type 2 diabetes. In this setting, weight loss is a major confounding factor that impedes clarification of the real effect of amending metabolic control. Obesity is frequently associated with type 2 diabetes and shows a proportional reduction in FVC and FEV1, suggesting the occurrence of restrictive lung disease (12,13). Moreover, improvements in lung function after weight loss, including FEV1 and FVC, have also been reported in obese patients (14).

To shed light on this issue, we performed a prospective and interventional study to determine whether improving type 2 diabetes metabolic control during a 3-month period was accompanied by significant changes in respiratory function. To minimize the impact of weight reduction on the same pulmonary parameters, subjects who experienced a BMI decrease ≥2.0 kg/m2 were excluded from the analysis.

Research Design and Methods

Statement on Ethics

The human ethics committee from the Hospital Universitari Arnau de Vilanova approved the study. Informed written consent was obtained from all participants included in the study, which was conducted according to the ethical guidelines of the Declaration of Helsinki.

Study Design and Description of the Study Population

This prospective interventional study examined the effect of the improvement of glycemic control on respiratory function in subjects with type 2 diabetes without any known pulmonary disease. The study examined a total of 594 consecutive Caucasian subjects with type 2 diabetes at their initial visit to the outpatient Diabetes Clinic from March 2016 to January 2018 (Supplementary Fig. 1). The inclusion criteria were as follows: age between 40 and 70 years, a BMI <40 kg/m2, HbA1c ≥7.5% (58 mmol/mol), no medical history of lung disease, and type 2 diabetes with at least 5 years of follow-up. Among the 340 patients who met the inclusion criteria, we excluded 125 for the following reasons: unwillingness to participate in the study (n = 37), hyperglycemia secondary to use of corticosteroids (n = 28), an inability to perform the spirometric maneuvers correctly (n = 25), active malignancy or malignancy diagnosed within the previous 5 years (n = 18), heart failure (n = 11), pregnancy (n = 4), and goiter with compressive symptoms (n = 2). Finally, spirometry was performed in 215 subjects, and only those with a baseline FEV1 ≤90% (n = 83) were invited to repeat spirometric maneuvers after a 3-month period, during which antidiabetic therapy was intensified. Four patients failed to perform the final evaluation. In addition, in order to minimize the influence of weight loss on the results, 19 patients who experienced a BMI reduction >2.0 kg/m2 were excluded. Finally, 60 patients were included in the study. Those with a reduction of their HbA1c of ≥0.5% (arbitrary set point) were considered to be good responders (n = 35), and the other 25 patients to be nonresponders.

At baseline and at the end of the study, a Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) (15) and the equation proposed by Bonora et al. (16) were used to estimate total body fat and abdominal fat, respectively.

A control group of 34 healthy subjects, without type 2 diabetes or lung disease, was recruited from January 2017 to January 2018 from among the relatives of patients with diabetes, as well as the employees of our institution.

Measurement of Respiratory Function Data

Forced spirometry was measured using a Datospir Micro C spirometer (Sibelmed, Barcelona, Spain) and carried out under the guidelines proposed by the European Respiratory Society (17). The different spirometric parameters were measured as a percentage of the predicted values, and included FEV1, FVC, peak expiratory flow (PEF), forced expiratory flow between 25% and 75% of the FVC (FEF25–75), and the ratio between FEV1 and FVC (FVE1/FVC). Before each assessment, the procedure was demonstrated to the patient, who was asked to make some practice efforts. Subjects were required to perform a minimum of three reproducible measurements, and the output that produced the highest sum of FEV1 and FVC was chosen for analysis.

In accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD), a nonobstructive ventilatory defect was defined by an FVC of <80% of the predicted value, with an FEV1/FVC ratio ≥70% (18). An abnormal FEV1 was defined as a value <80% of that predicted. Similarly, an obstructive ventilatory defect was defined by an FEV1/FVC ratio <70% of the predicted value (18).

Type 2 Diabetes Treatment at Baseline and During Glycemic Improvement

At baseline, patients were treated with metformin alone (8.3%), metformin plus other oral agents (26.6%), basal insulin alone (31.6%), or with a basal-bolus regimen (25.0%), glucagon-like peptide 1 (GLP-1) receptor agonists (3.3%) plus oral agents, and basal insulin associated with GLP-1 (5.0%). No patient was treated with diet alone.

All subjects underwent treatment intensification to improve glycemic control according to our routine medical practice. At the end of the study, the proportion of patients receiving insulin therapy increased to 66.6%; 23.3% were treated with GLP-1 receptor agonists (10 of the 14 patients receiving GLP-1 in combination with insulin). None of the subjects continued receiving treatment comprising only diet or metformin.

Statistical Analysis

Statistical analyses were performed using SPSS software (Statistics for Windows, version 20.0.; IBM, Armonk, NY). A normal distribution of the variables was established using the Kolmogorov-Smirnov test, and data are expressed as the mean ± SD, median (range), or percentage. A paired Student t test was used to compare the baseline data with those obtained at the end of follow-up, whereas categorical variables were compared using the χ2 test. The relationship between continuous variables was examined by the Pearson linear correlation test. A stepwise multivariate regression analysis was performed to explore the variables independently related to the absolute change of FEV1, FVC, PEF, and FEF25–75. Variables significantly associated with changes in lung function in the bivariate analysis (i.e., age, baseline HbA1c, and the absolute change in HbA1c), together with clinically relevant variables with a potential impact on lung function (i.e., sex, BMI, smoking habit, and type 2 diabetes duration) were included in the analysis. All P values were based on a two-sided test of statistical significance. Significance was accepted at a level of P < 0.05.

Results

The main clinical features and metabolic data of the study population are presented in Table 1. After a mean follow-up period of 80.0 ± 8.6 days, 35 patients (58.3%) were classified as good responders. In this group, HbA1c had significantly decreased from 9.1 ± 1.2% to 7.1 ± 0.7% (71.1 ± 14.0 to 48.3 ± 8.0 mmol/mol, P < 0.001). On the other hand, 25 patients (41.7%) were classified as nonresponders, with a mean change in HbA1c of 0.2% (95% CI −0.1 to 0.3). Changes in BMI were not significant in either group after this follow-up period (P = 0.103 in good responders, P = 0.398 in nonresponders). Apart from a higher baseline HbA1c (9.1 ± 1.2% vs. 8.4 ± 1.1%, P = 0.025) and FPG (224.1 ± 65.5 vs. 170.4 ± 66.0 mg/dL, P = 0.003) in the responder group, no other differences were observed between both groups. Baseline pulmonary parameters were also similar in either good responders or nonresponders.

View this table:
  • View inline
  • View popup
Table 1

Baseline main clinical, metabolic, and pulmonary characteristics of participants in the study according to their response to the intensification of antidiabetic treatment

Spirometric values (FVC, FEV1, PEF, FEF25–75, and FEV1/FVC) did not change between baseline and the end of the study when the group of nonresponders was evaluated (Table 2). However, subjects who exhibited a significant improvement in their metabolic control also revealed a positive and significant impact in their FVC (78.5 ± 12.6 at baseline vs. 83.3 ± 14.7 at the end of study, P = 0.029), FEV1 (75.6 ± 15.3 vs. 80.9 ± 15.4, P = 0.010), and PEF (80.4 ± 21.6 vs. 89.2 ± 21.0, P = 0.007) values. These changes were similar when pulmonary function was assessed in the entire population. In the control group, spirometric values did not change between baseline and after a follow-up period of 84.5 ± 36.3 days, similar to the group of nonresponders (Supplementary Table 1).

View this table:
  • View inline
  • View popup
Table 2

Evolution of the main pulmonary function parameters according the response to the intensification of the antidiabetic treatment

At the end of follow-up, 30 subjects were receiving insulin treatment (50.0%), 4 subjects were receiving GLP-1 receptor agonist treatment (6.6%), and 10 subjects were receiving treatment with insulin plus GLP-1 receptor agonist (16.6%). The spirometric measurements at baseline and after the metabolic improvement period in these three groups did not experience significant changes (Supplementary Table 2).

According to the GOLD criteria, almost one of every two patients at baseline showed a nonobstructive ventilatory defect, which decreased significantly at the end of the intensification period (56.6% vs. 40.0%, P = 0.007). When these data were evaluated according to the response to antidiabetic treatment intensification, the improvement was only significant among good responders (57.1% vs. 28.5%, P = 0.022) (Table 2). Similarly, the percentage of subjects with an abnormal FEV1 value only decreased significantly among good responders (51.4% vs. 40.0%, P < 0.001).

Univariate analysis showed that the absolute decrease in HbA1c was correlated to increases in FEV1 (r = −0.402, P = 0.001 in the entire population; r = −0.370, P = 0.029 in the responder group) and PEF (r = −0.348, P = 0.006 in the entire population; r = −0.471, P = 0.004 in the responder group) (Table 3). In addition, a similar correlation was observed between the absolute decrease in HbA1c and increments in FEF25–75 in the responder group (r = −0.335, P = 0.049). The rest of the correlations observed in the univariate analysis are displayed in Supplementary Table 3.

View this table:
  • View inline
  • View popup
Table 3

Correlations of the absolute changes in HbA1c with changes in spirometric values obtained in the univariate analyses

Finally, stepwise multivariate regression analysis showed that the absolute change in HbA1c (but not age, sex, known years with type 2 diabetes, smoking status, absolute change in the BMI, and the baseline FEV1) independently predicted increased FEV1 (R2 = 0.174) (Table 4). In addition, the absolute change in HbA1c, together with baseline PEF, independently predicted changes in PEF (R2 = 0.309). However, the known duration of type 2 diabetes, but not the amelioration of HbA1c, was related to changes in FEF25–75.

View this table:
  • View inline
  • View popup
Table 4

Variables independently related to changes in sprirometric measurements in the multiple regression analysis (stepwise method)

Conclusions

To the best of our knowledge, this is the first study to provide evidence that spirometric maneuvers in patients with type 2 diabetes exhibit significant amelioration after a short improvement in glycemic control. The favorable change in the spirometric parameters was present only in the group of patients who achieved a final reduction of their HbA1c >0.5%, reinforcing the idea that the lungs should be considered as an end target of chronic hyperglycemia. Interestingly, the most sensitive spirometric parameters for this rapid amelioration of metabolic control were associated with intrapulmonary airway caliber and neuromuscular integrity (19,20). Our data, obtained from patients without known pulmonary disease, also suggest that the duration of type 2 diabetes is related with a more irreversible impact in distal obstruction (21). It should be noted that in our study, the group of “good responders” experienced a 6.4% increase in their FEV1 after the 3-month period of metabolic improvement. In the Fremantle Diabetes Study (6), a 10% decrease in FEV1 was associated with a 12% increase in all-cause mortality. Therefore, it seems reasonable to postulate that the impact of the improvement of glycemic control on pulmonary function could have positive clinical consequences. However, larger studies and with longer follow-up are needed to examine this crucial point.

The bronchiolar surfactant layer is involved in maintaining airway stability and caliber, and, when damaged, surfactant proteins migrate into the bloodstream from the alveolar space (22). In this way, the underlying deficit in GLP-1 in type 2 diabetes could be involved in the impairment of airway caliber. The GLP-1 receptor is abundant in the lungs, and it has played a role in the stimulation of pulmonary surfactant production by type II alveolar cells in experimental studies (23,24). In fact, in a rat model with streptozotocin-induced diabetes, the reduced level of surfactant proteins was restored after the administration of liraglutide, a GLP-1 receptor agonist (25). López-Cano et al. (4) have recently communicated how serum concentrations of surfactant protein D are independently associated with an abnormal FEV1 level in obese subjects with type 2 diabetes, suggesting its measurement for identifying patients requiring a pulmonary function examination. Therefore, the potential pulmonary benefit of incretin-based therapies seems particularly relevant, and a clinical trial aimed at answering this question is ongoing (clinical trial reg. no. NCT02889510, ClinicalTrials.gov). However, in our study, antidiabetic therapy with GLP-1 receptor agonist was added only in nine patients, and no conclusion could be obtained.

The role of other antidiabetic drugs in lung function remains unclear, since most studies are cross-sectional, which precludes the establishment of any causal links. In the Copenhagen City Heart Study, which comprised 323 subjects with type 2 diabetes and 68 patients with type 1 diabetes, lung injury was slightly more pronounced in those subjects treated with insulin in comparison with those treated with oral agents or diet (26). Although this finding might suggest a deleterious effect of insulin, it is more reasonable to attribute this relationship to the severity and duration of diabetes rather than to the insulin itself. In fact, type II alveolar cells also express insulin receptors that favor surfactant synthesis (27). In our study, the number of years since the time of type 2 diabetes diagnosis was independently related to changes in FEF25–75 in the multivariate analysis.

The contribution of IR in initiating lung abnormalities also deserves attention. First, lung function measures were inversely associated with IR in the British Women’s Heart and Health Study (28). In addition, IR was recognized as an independent predictor of altered airway resistance in morbidly obese women without diabetes (29). In a cross-sectional study investigating 196 patients, Vargas et al. (30) evaluated pulmonary function among those receiving metformin or secretagogues. After adjustment for metabolic control and the duration of the disease, the metformin group showed significantly lower differences from the expected values of FVC compared with those treated with secretagogues. In addition, the beneficial effect of metformin on sleep breathing disorders through its capacity to reduce the IR has also been documented. In nonobese rats, metformin administration not only prevented but also reversed the development of apnea episodes (31). In our study, the role of insulin-sensitizer therapies on the respiratory parameters seem negligible because neither metformin nor thiazolidinediones were added to treatment during follow-up. The double effect of weight loss on the amelioration of lung function and IR is an important confounding factor when evaluating the effect of treatment intensification in patients with type 2 diabetes. We have tried to avoid this by excluding patients who experienced a BMI reduction ≥2.0 kg/m2 during the study follow-up. In addition, in the multivariate regression analysis, the absolute change in HbA1c independently predicted increased FEV1. Therefore, our data support the independent and deleterious impact of type 2 diabetes in lung function tests.

In addition, data from the current study reinforce the theory that diabetes not only influence airway caliber, as also the nonobstructive pattern was highly prevalent in the study population and significantly decreased with the improvement of metabolic control. Although measurements of the FEV1 and PEF are similar, the interpretation may differ, either in repeatability or in the interpretation of what is being measured, and their values cannot be interchanged with certainty (19). The PEF represents a direct measurement of airway obstruction, but it is also an index of explosive abdominal and intercostal muscle strength as well as reflecting the elastic recoil of the lung and chest wall (19,20). In this way, the lungs are rich in collagen and elastin fibers, which are crucial proteins of the extracellular matrix, and might be involved in the development of a nonobstructive pulmonary defect. Thus, it has been suggested that nonenzymatic glycosylation of these proteins may contribute to lung damage in chronic hyperglycemia. Previous data evaluated the potential association between advanced glycation end products (AGEs) and lung function in patients with chronic obstructive pulmonary disease, in which higher skin AGE deposition and plasma AGE concentration had been reported (32). Recently, this relation also has been assessed in 1,924 Caucasian subjects without pulmonary disease according to the presence of glucose abnormalities (33). This cross-sectional study demonstrated that skin autofluorescence, a surrogate measurement of AGE, was related to a significant decrease in FVC and FEV1 values, which was aggravated among subjects with type 2 diabetes (33).

There are some potential limitations that should be considered in evaluating the results of our study. First, we evaluated a relatively small number of patients with type 2 diabetes, those willing to participate and those with low baseline pulmonary function, which means that no conclusive clinical consequences can be inferred to the general population of patients with type 2 diabetes. However, the patients included in the study were carefully selected, with confounding factors associated with lung function, such as weight changes, being avoided, and a control group of nonresponders being introduced. Therefore, it could not be argued that after a first experience with spirometric evaluation, subjects became better at performing the second spirometric assessment. Second, we did not have specific measurements of the physical exercise performed during follow-up, and, therefore, a potential bias related to the improvement of lung function due to increased cardiorespiratory fitness cannot be ruled out. However, the general information on lifestyle measures given to the subjects with diabetes were the same in “responders” and “nonresponders,” so that it is unlikely to have had any influence in the results. Third, our study provides evidence only of the beneficial effect of short-term glycemic improvement on functional long parameters, and long-term studies to confirm our findings seem warranted.

In conclusion, a short-term improvement in glycemic control was accompanied by positive changes in spirometric maneuvers in patients with type 2 diabetes. In addition, the improvement of metabolic control was mainly associated with central airway caliber and explosive muscle strength measurements. Although the mechanisms are not yet fully understood, our results draw attention to the need for strategies for identifying patients with type 2 diabetes who are more vulnerable for pulmonary involvement. Additional studies with a wide range of patients with type 2 diabetes and a longer intervention period are needed to confirm the amelioration of lung function after glycemic optimization.

Article Information

Funding. This study was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria, PI 12/00803 and PI 15/00260), European Union, European Regional Development Fund (Fondo Europeo de Desarrollo Regional, FEDER, “Una manera de hacer Europa”), Fundación Sociedad Española de Endocrinología y Nutrición (SEEN), and Menarini Spain S.A. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and CIBER de Enfermedades Respiratorias (CIBERES) are initiatives of the Instituto de Salud Carlos III.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Author Contributions. L.G.-C. and E.S. recruited patients, collected and analyzed the data, wrote the first draft of the manuscript, and had final approval of the version for publication. F.B. supervised the research, interpreted the data, and critically reviewed the draft of the manuscript. M.D. collected and analyzed the data and critically reviewed the draft of the manuscript. C.L.-C., M.H., and F.R. recruited patients, collected the data, and contributed to the discussion. P.C. collected and analyzed the data and contributed to the discussion. C.H. and R.S. designed the study, supervised the statistical analysis, interpreted the data, critically revised the draft of the manuscript, and had final approval of the version for publication. A.L. designed the study, supervised the research, analyzed and interpreted the data, and wrote the manuscript. A.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Footnotes

  • This article is featured in a podcast available at http://www.diabetesjournals.org/content/diabetes-core-update-podcasts.

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-1948/-/DC1.

  • Received September 16, 2018.
  • Accepted January 8, 2019.
  • © 2019 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

References

  1. ↵
    1. van den Borst B,
    2. Gosker HR,
    3. Zeegers MP,
    4. Schols AMWJ
    . Pulmonary function in diabetes: a metaanalysis. Chest 2010;138:393–406pmid:20348195
    OpenUrlCrossRefPubMedWeb of Science
    1. Lecube A,
    2. Sampol G,
    3. Muñoz X,
    4. Hernández C,
    5. Mesa J,
    6. Simó R
    . Type 2 diabetes impairs pulmonary function in morbidly obese women: a case-control study. Diabetologia 2010;53:1210–1216pmid:20217039
    OpenUrlPubMed
  2. ↵
    1. Lecube A,
    2. Simó R,
    3. Pallayova M, et al
    . Pulmonary function and sleep breathing: two new targets for type 2 diabetes care. Endocr Rev 2017;38:550–573pmid:28938479
    OpenUrlPubMed
  3. ↵
    1. López-Cano C,
    2. Lecube A,
    3. García-Ramírez M, et al
    . Serum surfactant protein D as a biomarker for measuring lung involvement in obese patients with type 2 diabetes. J Clin Endocrinol Metab 2017;102:4109–4116pmid:28945872
    OpenUrlPubMed
  4. ↵
    1. Barrett-Connor E,
    2. Frette C
    . NIDDM, impaired glucose tolerance, and pulmonary function in older adults. The Rancho Bernardo Study. Diabetes Care 1996;19:1441–1444pmid:8941481
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Davis WA,
    2. Knuiman M,
    3. Kendall P,
    4. Grange V,
    5. Davis TM; Fremantle Diabetes Study
    . Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care 2004;27:752–757pmid:14988297
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Walter RE,
    2. Beiser A,
    3. Givelber RJ,
    4. O’Connor GT,
    5. Gottlieb DJ
    . Association between glycemic state and lung function: the Framingham Heart Study. Am J Respir Crit Care Med 2003;167:911–916pmid:12623860
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    1. Yeh HC,
    2. Punjabi NM,
    3. Wang NY, et al
    . Cross-sectional and prospective study of lung function in adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care 2008;31:741–746pmid:18056886
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Davis TM,
    2. Knuiman M,
    3. Kendall P,
    4. Vu H,
    5. Davis WA
    . Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Res Clin Pract 2000;50:153–159pmid:10960726
    OpenUrlPubMedWeb of Science
  9. ↵
    1. Lecube A,
    2. Sampol G,
    3. Lloberes P, et al
    . Diabetes is an independent risk factor for severe nocturnal hypoxemia in obese patients. A case-control study. PLoS One 2009;4:e4692pmid:19262746
    OpenUrlCrossRefPubMed
  10. ↵
    1. Lecube A,
    2. Ciudin A,
    3. Sampol G,
    4. Valladares S,
    5. Hernández C,
    6. Simó R
    . Effect of glycemic control on nocturnal arterial oxygen saturation: a case-control study in type 2 diabetic patients. J Diabetes 2015;7:133–138pmid:25043292
    OpenUrlPubMed
  11. ↵
    1. Brazzale DJ,
    2. Pretto JJ,
    3. Schachter LM
    . Optimizing respiratory function assessments to elucidate the impact of obesity on respiratory health. Respirology 2015;20:715–721pmid:26033636
    OpenUrlPubMed
  12. ↵
    1. Yeh F,
    2. Dixon AE,
    3. Marion S, et al
    . Obesity in adults is associated with reduced lung function in metabolic syndrome and diabetes: the Strong Heart Study. Diabetes Care 2011;34:2306–2313pmid:21852681
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Pakhale S,
    2. Baron J,
    3. Dent R,
    4. Vandemheen K,
    5. Aaron SD
    . Effects of weight loss on airway responsiveness in obese adults with asthma: does weight loss lead to reversibility of asthma? Chest 2015;147:1582–1590pmid:25763936
    OpenUrlCrossRefPubMed
  14. ↵
    1. Gómez-Ambrosi J,
    2. Silva C,
    3. Catalán V, et al
    . Clinical usefulness of a new equation for estimating body fat. Diabetes Care 2012;35:383–388pmid:22179957
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Bonora E,
    2. Micciolo R,
    3. Ghiatas AA, et al
    . Is it possible to derive a reliable estimate of human visceral and subcutaneous abdominal adipose tissue from simple anthropometric measurements? Metabolism 1995;44:1617–1625pmid:8786733
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    1. Miller MR,
    2. Hankinson J,
    3. Brusasco V, et al.; ATS/ERS Task Force
    . Standardisation of spirometry. Eur Respir J 2005;26:319–338pmid:16055882
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Vogelmeier CF,
    2. Criner GJ,
    3. Martinez FJ, et al
    . Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 2017;195:557–582pmid:28128970
    OpenUrlCrossRefPubMed
  18. ↵
    1. Ruffin R
    . Peak expiratory flow (PEF) monitoring. Thorax 2004;59:913–914pmid:15516458
    OpenUrlPubMed
  19. ↵
    1. Quanjer PH,
    2. Tammeling GJ,
    3. Cotes JE,
    4. Pedersen OF,
    5. Peslin R,
    6. Yernault JC
    . Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 1993;16:5–40pmid:8499054
    OpenUrlPubMedWeb of Science
  20. ↵
    1. Pellegrino R,
    2. Viegi G,
    3. Brusasco V, et al
    . Interpretative strategies for lung function tests. Eur Respir J 2005;26:948–968pmid:16264058
    OpenUrlFREE Full Text
  21. ↵
    1. Hartl D,
    2. Griese M
    . Surfactant protein D in human lung diseases. Eur J Clin Invest 2006;36:423–435pmid:16684127
    OpenUrlCrossRefPubMed
  22. ↵
    1. Körner M,
    2. Stöckli M,
    3. Waser B,
    4. Reubi JC
    . GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med 2007;48:736–743pmid:17475961
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Vara E,
    2. Arias-Díaz J,
    3. García C,
    4. Balibrea JL,
    5. Blázquez E
    . Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes. Am J Respir Crit Care Med 2001;163:840–846pmid:11282754
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    1. Romaní-Pérez M,
    2. Outeiriño-Iglesias V,
    3. Moya CM, et al
    . Activation of the GLP-1 receptor by liraglutide increases ACE2 expression, reversing right ventricle hypertrophy, and improving the production of SP-A and SP-B in the lungs of type 1 diabetes rats. Endocrinology 2015;156:3559–3569pmid:26196539
    OpenUrlPubMed
  25. ↵
    1. Lange P,
    2. Groth S,
    3. Kastrup J, et al
    . Diabetes mellitus, plasma glucose and lung function in a cross-sectional population study. Eur Respir J 1989;2:14–19pmid:2651148
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Shapiro DL,
    2. Livingston JN,
    3. Maniscalco WM,
    4. Finkelstein JN
    . Insulin receptors and insulin effects on type II alveolar epithelial cells. Biochim Biophys Acta 1986;885:216–220pmid:3511973
    OpenUrlPubMed
  27. ↵
    1. Lawlor DA,
    2. Ebrahim S,
    3. Smith GD
    . Associations of measures of lung function with insulin resistance and type 2 diabetes: findings from the British Women’s Heart and Health Study. Diabetologia 2004;47:195–203pmid:14704837
    OpenUrlCrossRefPubMedWeb of Science
  28. ↵
    1. Lecube A,
    2. Sampol G,
    3. Muñoz X,
    4. Lloberes P,
    5. Hernández C,
    6. Simó R
    . Insulin resistance is related to impaired lung function in morbidly obese women: a case-control study. Diabetes Metab Res Rev 2010;26:639–645pmid:20882512
    OpenUrlPubMed
  29. ↵
    1. Vargas HA,
    2. Rondón M,
    3. Dennis R
    . Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study. Biomedica 2016;36:276–284pmid:27622489
    OpenUrlPubMed
  30. ↵
    1. Ramadan W,
    2. Dewasmes G,
    3. Petitjean M, et al
    . Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats. Obesity (Silver Spring) 2007;15:1409–1418pmid:17557978
    OpenUrlPubMed
  31. ↵
    1. Hoonhorst SJ,
    2. Lo Tam Loi AT,
    3. Hartman JE, et al
    . Advanced glycation end products in the skin are enhanced in COPD. Metabolism 2014;63:1149–1156pmid:25034386
    OpenUrlPubMed
  32. ↵
    Sánchez E, Lecube A, Betriu À, et al.; ILERVAS Project. Subcutaneous advanced glycation end-products and lung function according to glucose abnormalities: The ILERVAS Project. Diabetes Metab. 13 April 2018 [Epub ahead of print]. DOI: 10.1016/j.diabet.2018.04.00210.1016/j.diabet.2018.04.002
PreviousNext
Back to top
Diabetes Care: 42 (4)

In this Issue

April 2019, 42(4)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Masthead (PDF)
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study
Liliana Gutiérrez-Carrasquilla, Enric Sánchez, Ferran Barbé, Mireia Dalmases, Carolina López-Cano, Marta Hernández, Ferran Rius, Paola Carmona, Cristina Hernández, Rafael Simó, Albert Lecube
Diabetes Care Apr 2019, 42 (4) 617-624; DOI: 10.2337/dc18-1948

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study
Liliana Gutiérrez-Carrasquilla, Enric Sánchez, Ferran Barbé, Mireia Dalmases, Carolina López-Cano, Marta Hernández, Ferran Rius, Paola Carmona, Cristina Hernández, Rafael Simó, Albert Lecube
Diabetes Care Apr 2019, 42 (4) 617-624; DOI: 10.2337/dc18-1948
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Research Design and Methods
    • Results
    • Conclusions
    • Article Information
    • Footnotes
    • References
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort
  • Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes
  • High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes
Show more Pathophysiology/Complications

Similar Articles

Subjects

  • Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.