Exploring the Role of Adipocyte Fatty Acid Binding Protein in the Association of Obstructive Sleep Apnea and Metabolic Dysfunction

Randomized Controlled Trial of the Effect of Continuous Positive Airway Pressure on Adipocyte Fatty Acid Binding Protein and Other Metabolic Markers in Obstructive Sleep Apnea

Adipocyte fatty acid binding protein (A-FABP) is a member of the FABP super family, is abundant in adipocytes and macrophages. Regulatory functions of A-FABP in lipid and glucose metabolism have been described, and it is suggested to play an important role in the pathogenesis of metabolic syndrome.We hypothesize that obstructive sleep apnea (OSA) may upregulate A-FABP production and thus causally contribute to metabolic dysfunction. Our group has recently demonstrated that A-FABP, expressed and secreted from adipocytes, is present in the blood stream .The levels of A-FABP correlated with various metabolic variates in the metabolic syndrome. Furthermore, we have obtained novel data in men with a range of sleep disordered breathing showed that the duration of oxygen desaturation correlated with circulating levels of A-FABP, independent of age and waist/body mass index. The current proposal aims to pursue this finding and further explore the role of A-FABP in the association of OSA and metabolic dysfunction.

Study Overview

• Status: Completed
• Conditions: Inflammation; Metabolic Syndrome; Insulin Resistance; Obstructive Sleep Apnea
• Intervention / Treatment: Device: continuous positive airway pressure

Detailed Description

We hypothesize that there are changes in circulating A-FABP level which can be mitigated by effective treatment of OSA.

The aim is to investigate the effect of CPAP treatment of OSA on circulating A-FABP, and other metabolic biomarkers and cardiovascular parameters

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong, 852
    • The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects between 18 - 65 years old
• Able to understand and give informed written consent

Exclusion Criteria:

• BMI > 35 kg/m2, and features of obesity hypoventilation syndrome
• known diabetes mellitus or hyperlipidemia on treatment
• known cardiovascular disease except hypertension stable on treatment
• unstable medical illness
• need for starting treatment for OSA or other medical conditions immediately

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: continuous positive airway pressure; using continuous positive airway pressure (CPAP) device during sleep, for the study period (4 weeks)	Device: continuous positive airway pressure; an device to be used during sleep, which was a nasal mask connected to a device with pressure applied to upper airway
No Intervention: control; observation for the study period (4 weeks, no CPAP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adipocyte fatty acid binding protein	blood assay	changes over 4 weeks of CPAP treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin and glucose	blood assay	changes over 4 weeks of CPAP treatment
Lipids and lipoprotein	blood assay	changes over 4 weeks of CPAP treatment
blood Markers of oxidative stress and fat metabolism		changes over 4 weeks of CPAP treatment
blood inflammatory markers		changes over 4 weeks of CPAP treatment
blood pressure		changes over 4 weeks of CPAP treatment
Epworth sleepiness scale	by sleep questionnaire	changes over 4 weeks of CPAP treatment

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Mary SM Ip, MD, The University of Hong Kong, Queen Mary Hospital

Publications and helpful links

General Publications

• Xu A, Wang Y, Xu JY, Stejskal D, Tam S, Zhang J, Wat NM, Wong WK, Lam KS. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem. 2006 Mar;52(3):405-13. doi: 10.1373/clinchem.2005.062463. Epub 2006 Jan 19.
• Stejskal D, Karpisek M. Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome? Eur J Clin Invest. 2006 Sep;36(9):621-5. doi: 10.1111/j.1365-2362.2006.01696.x.
• Lam DC, Xu A, Lam KS, Lam B, Lam JC, Lui MM, Ip MS. Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance. Eur Respir J. 2009 Feb;33(2):346-51. doi: 10.1183/09031936.50075408.
• Lui MMS, Mak JCW, Chong PWC, Lam DCL, Ip MSM. Circulating adipocyte fatty acid-binding protein is reduced by continuous positive airway pressure treatment for obstructive sleep apnea-a randomized controlled study. Sleep Breath. 2020 Sep;24(3):817-824. doi: 10.1007/s11325-019-01893-5. Epub 2019 Aug 1.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 29, 2010
• First Submitted That Met QC Criteria: July 30, 2010
• First Posted (Estimate): August 2, 2010

Study Record Updates

• Last Update Posted (Actual): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: obstructive sleep apnea; metabolic syndrome; adipocyte fatty acid binding protein; metabolic dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Hyperinsulinism; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Inflammation; Apnea; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: UW07-178; HKCTR-770 (Registry Identifier: Clinical trial centre, The University of Hong Kong)