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Insulin resistance may contribute to vascular dysfunction in patients with chronic obstructive pulmonary disease

Insulinresistenz bei Patienten mit COPD möglicherweise an vaskulärer Dysfunktion beteiligt

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Summary

Background

Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function.

Methods

We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28–55 %); body mass index: 26 kg/m2 (24–28 kg/m2)] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months.

Results

Flow-mediated dilation significantly decreased from 13.5 % (11–15 %) at baseline to 9.8 % (6–12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86–103 mg/dl) to 102 mg/dl (94–111 mg/dl; p = 0.027) and from 1.2 (0.8–2.1) to 1.7 (1.2–3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = − 0.483, p = 0.009), HOMA-IR (r = − 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05).

Conclusion

Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.

Zusammenfassung

Grundlagen

Patienten mit Chronisch Obstruktiver Lungenerkrankung (COPD) sind einem erhöhten kardiovaskulären Risiko ausgesetzt; die zugrundeliegenden Mechanismen für diesen Zusammenhang sind jedoch nicht gänzlich bekannt. Ein gestörter Glukosemetabolismus könnte via endothelialer Dysfunktion das kardiovaskuläre Risiko erhöhen.

Methodik

Wir führten eine prospektive Pilotstudie durch, um die Zusammenhänge zwischen systemischer Gefäßfunktion, Glukosemetabolismus, und Lungenfunktion bei Patienten mit COPD zu untersuchen. Achtzehn Patienten mit stabiler moderat-schwerer COPD (Nichtraucher, 67 % Männer; medianer (1. bis 3. Quartile) FEV1 % Soll 38 % (28–55 %); Body mass index 26 kg/m2 (24–28 kg/m2)) ohne relevante kardiovaskuläre Risikofaktoren wurden untersucht. Die systemische Gefäßfunktion wurde anhand der Fluss-mediierten Dilatation der Arteria brachialis determiniert. Die erhobenen Laborparameter umfassten die Bestimmung des Nüchternblutzuckerspiegel, zirkulierende Insulinkonzentrationen, C-reaktives Protein, und Fibrinogen. Der Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index wurde errechnet. Alle Untersuchungen wurden zum Zeitpunkt der Erstuntersuchung durchgeführt und nach 12 Monaten wiederholt.

Ergebnisse

Die Fluss-mediierte Dilatation der Arteria brachialis nahm von 13,5 % (11–15 %) zum Zeitpunkt der Erstuntersuchung auf 9,8 % (6–12 %) (p = 0,002) nach 12 Monaten ab, der Nüchternblutzuckerspiegel hingegen stieg im gleichen Zeitraum von 94 mg/dl (86–103 mg/dl) auf 102 mg/dl (94–111 mg/dl) (p = 0,027) und der HOMA-IR Index von 1.2 (0,8–2,1) auf 1,7 (1,2–3,0) (p = 0,023) an. Es zeigt sich ein statistisch signifikanter Zusammenhang zwischen den Veränderungen der endothelialen Dysfunktion und dem Nüchternblutzuckerspiegel (r = − 0,483, p = 0,009), HOMA-IR (r = − 0,441, p = 0,019), und FEV1 (r = 0.336, p = 0.05).

Schlussfolgerung

Ein veränderter Glukosemetabolismus scheint mit einer Progression der endothelialen Dysfunktion bei Patienten verbunden zu sein.

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Acknowledgments

The authors thank the laboratory staff from the Otto Wagner Hospital and the Department of Clinical Pharmacology (Medical University Vienna) for their help in analyzing the blood samples. This research was supported by the Ludwig Boltzmann Institute for COPD, Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria.

Conflict of interest

Otto C. Burghuber has been serving on advisory board meetings for Boehringer Ingelheim RCV Austria and Nycomed Austria. He has received honorary and consultancy fees from Boehringer Ingelheim, Glaxo-Smith-Kline, Nycomed, and Astra Zeneca not exceeding the amount of $ 5,000 per year. Dr. Burghuber further received unrestricted research support grants from Boehringer-Ingelheim and Astra Zeneca over the past years. Arschang Valipour has been serving on advisory board meetings for Boehringer Ingelheim RCV Austria. He has received honorary and consultancy fees from Boehringer Ingelheim and Astra Zeneca not exceeding the amount of $ 5,000 per year. The other authors declare that they have no competing interests. Matthias Urban, Leyla Ay, Georg-Christian Funk, Philipp Eickhoff, and Michael Wolzt have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Ludwig Boltzmann Institute for COPD, Otto Wagner Hospital, Sanatoriumstrasse 2, 1140, Vienna, Austria

    Matthias Helmut Urban MD,  Georg-Christian Funk,  Otto Chris Burghuber &  Arschang Valipour MD, FCCP

  2. 1st Department of Internal Medicine, Rudolfstiftung, Juchgasse 25, 1030, Vienna, Austria

    Leyla Ay MD

  3. St. Anna Childrens Hospital, Kinderspitalgasse 6, 1090, Vienna, Austria

    Philipp Eickhoff MD

  4. Department of Clinical Pharmacology, Medical University Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Michael Wolzt

Authors
  1. Matthias Helmut Urban MD
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  2. Leyla Ay MD
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  3. Georg-Christian Funk
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  4. Otto Chris Burghuber
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  5. Philipp Eickhoff MD
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  6. Michael Wolzt
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  7. Arschang Valipour MD, FCCP
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Corresponding author

Correspondence to Arschang Valipour MD, FCCP.

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Urban, M., Ay, L., Funk, GC. et al. Insulin resistance may contribute to vascular dysfunction in patients with chronic obstructive pulmonary disease. Wien Klin Wochenschr 126, 106–112 (2014). https://doi.org/10.1007/s00508-013-0478-0

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  • DOI: https://doi.org/10.1007/s00508-013-0478-0

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