Fat Metabolism in OSA and COPD

NCT02157844 | Completed

• 1 other identifier: 2013-0878F
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (OSA) is the most common type of sleep apnea and is caused by an obstruction of the upper airways. The obstruction results in periods of intermittent hypoxia and re-oxygenation, which lead to increased oxidative stress, increased inflammation, endothelial dysfunction, and insulin resistance. Chronic obstructive pulmonary disease (COPD) is a lung disease that leads to poor airflow. This disease leads to systemic hypoxia, reduced oxidative capacity, and increased inflammation. The direct cause of OSA and COPD is unclear, but OSA and COPD may be linked to other comorbid conditions such as obesity and type II diabetes. Upon onset of OSA and COPD, metabolic disturbances associated with obesity and type II diabetes can be exacerbated. Obesity is a condition characterized by an increase in visceral fat, elevated plasma levels of free fatty acids, inflammation, and insulin resistance. Although the effects of body fat distribution have not been studied in these patients, an increase in both subcutaneous and abdominal fat mass in non-OSA older women was shown to increase morbidity and mortality. Fat/adipose tissue is an active tissue capable of secreting proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, reactive oxygen species and adipokines. Particularly, abdominal fat is a prominent source of pro-inflammatory cytokines, which contributes to a low grade, chronic inflammatory state in these patients. Additionally, an increased inflammatory state is associated with reduced lean body mass, and together with elevated circulating free fatty acids may increase the occurrence of lipotoxicity and insulin resistance. Thus, increased fat deposition is associated with a poor prognosis in OSA and COPD patients and therefore it is of clinical and scientific importance to understand the changes in fat metabolism and digestion as a result of OSA and COPD. It is therefore our hypothesis that fat synthesis and insulin resistance is increased and whole body protein synthesis is decreased in OSA and COPD patients, leading to a poor prognosis.

Conditions

Obstructive Sleep Apnea; Chronic Obstructive Pulmonary Disease; Obesity

Keywords

Obstructive Sleep Apnea; Chronic Obstructive Pulmonary Disease; Obesity; Hepatic fat metabolism; fat digestion; whole body protein synthesis; protein digestion; amino acid metabolism; adipose tissue fat metabolism; lipolysis

Outcome Measures

Primary Outcomes (16)

• Hepatic triglyceride synthesis

  changes in hepatic triglyceride synthesis before and after a meal

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Hepatic de novo lipogenesis

  changes in hepatic de novo lipogenesis before and after a meal

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Adipose tissue triglyceride synthesis

  changes in adipose tissue triglyceride synthesis before and after a meal

  pre and 4 hours post meal

• Adipose tissue de novo lipogenesis

  changes in adipose tissue de novo lipogenesis before and after a meal

  pre and 4 hours post meal

• Adipose tissue lipolysis - glycerol rate of appearance

  changes in adipose tissue lipolysis before and after a meal. plasma enrichment of glycerol.

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Rate of appearance of ingested glucose

  determine changes in appearance of glucose rate in subjects

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Endogenous Glucose Production

  Determine whole body glucose production in subjects

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Glucose disposal

  Determine whole body glucose uptake in subjects

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Net whole-body protein synthesis

  change in whole-body protein synthesis rate after intake of meal

  0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

• Citrulline Rate of appearance

  plasma enrichment of citrulline

  Postabsorptive state during 2 hours

• Arginine turnover rate

  Arginine enrichment in plasma

  postabsorptive state during 3 hours

• Whole body collagen breakdown rate

  Hydroxyproline enrichment in plasma

  Postabsorptive state during 3 hours

• Tryptophan turnover rate

  Tryptophan enrichment in plasma

  Postabsorptive state during 3 hours

• Myofibrillar protein breakdown rate

  3methylhistidine enrichment in plasma

  0,15,30,45,60,75,90,105,120,150,180,210 min post-meal

• Glycine rate of appearance

  glycine enrichment in plasma

  Postabsorptive state during 3 hours

• Taurine turnover rate

  enrichment of taurine in

  postabsorptive state during 3 hours

Secondary Outcomes (5)

• Fat digestion and absorption

  Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion

• Insulin response to feeding

  pre and up to 5 hours post meal

• Body composition

  1 day

• Physical activity questionnaire

  1 day

• Protein digestion after feeding

  0,15,30,45,60,75,90,105,120,150,180,210, min post-meal

Study Arms (4)

COPD and OSA

Subjects with diagnosis of COPD and OSA

COPD

Subjects with diagnosis of COPD

OSA

Subjects with diagnosis of OSA

controls

Gender, age, BMI matched controls

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with OSA or COPD will be recruited when visiting a medical or pulmonary clinic in and outside the surrounding area of College Station. Patients and healthy subjects will also be recruited by responding to distributed flyers in the community in the College Station area; for example in hospital/clinic waiting areas, clinic rooms and bulletin boards at Scott \& White and the CSMC or any other hospital. Other general recruitment material in relation to the nutrition research that the research group performs at Texas A\&M can be placed on bulletin boards at Scott \& White and the CSMC.

You may qualify if:

• Established diagnosis of OSA or COPD
• Ability to sign informed consent
• Ability to walk, sit down and stand up independently
• Age 30 years and older
• Ability to lie in supine position for up to 8 hours
• Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease
• Willingness and ability to comply with the protocol
• Healthy male \& female according to the investigator's or appointed staff's judgment
• Ability to walk, sit down and stand up independently
• Age 30 years or older
• Ability to lay in supine or elevated position for 8 hours
• No diagnosis of OSA or COPD
• Willingness and ability to comply with the protocol

You may not qualify if:

• Established diagnosis of malignancy
• Untreated metabolic diseases including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Presence of fever within the last 3 days
• Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
• Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
• Use of protein or amino acid containing nutritional supplements within 5 days of first study day 5 days of first study day
• Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
• History of hypo- or hyper-coagulation disorders, including use of a Coumadin derivative, history of deep venous thrombosis (DVT), or pulmonary embolism (PE) at any point in lifetime
• Currently taking anti-thrombotics and cannot stop for 7 days (i.e. medical indication)
• Recent myocardial infarction ( \< 1 year ago)
• Current alcohol or drug abuse
• (Possible) pregnancy

Sponsors & Collaborators

• Texas A&M University: lead

Study Sites (1)

Texas A&M University

College Station, Texas, 77843, United States

Location

Related Publications (2)

• Deutz LN, Wierzchowska-McNew RA, Deutz NE, Engelen MP. Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity? Am J Clin Nutr. 2024 Jun;119(6):1455-1464. doi: 10.1016/j.ajcnut.2024.04.008. Epub 2024 Apr 12.

  PMID: 38616018 DERIVED

• Engelen MPKJ, Kirschner SK, Coyle KS, Argyelan D, Neal G, Dasarathy S, Deutz NEP. Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease. Clin Nutr. 2023 Sep;42(9):1737-1746. doi: 10.1016/j.clnu.2023.06.031. Epub 2023 Jul 26.

  PMID: 37542951 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Urine, adipose tissue, serum, plasma

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Pulmonary Disease, Chronic Obstructive; Obesity

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Study Officials

• Marielle Engelen, Ph.D.

  Texas A&M University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 4, 2014
• First Posted: June 6, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 4, 2022

Record last verified: 2022-02

Locations

US (1)