Lipolysis and Metabolic Impairment in Community-Based Sample with Obstructive Sleep Apnea R. Nisha Aurora, MD Assistant Professor of Medicine Division of Pulmonary & Critical Care Medicine Group 4
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse during sleep General population estimates: 9% in women and 24% in men OSA estimated prevalence of 86% in patients with type 2 diabetes mellitus OSA is associated with multiple adverse outcomes: CVD, MVA s, stroke, disorders of glucose metabolism 7/25/2014 2
Sleep Fragmentation Sleep Apnea Insulin Resistance Type 2 Diabetes Intermittent Hypoxemia
Adipose Tissue Free Fatty Acid Mobilization Insulin Resistance Type 2 Diabetes
Sleep Fragmentation Sleep Apnea Free Fatty Acid Mobilization Insulin Resistance Type 2 Diabetes Intermittent Hypoxemia
Two rigorous techniques will be utilized to yield critical data that will help advance our understanding of the relevance of adipocyte function in OSA and glucose metabolism: Adipose tissue microdialysis will be performed to assess levels of FFA at the cellular/tissue level. Fasting intravenous glucose tolerance testing (FIVGTT) will be conducted to determine insulin sensitivity. 7/25/2014 6
The overarching goals of the current proposal are to: Characterize the association between lipolysis and OSA and correlate this association with impaired glucose metabolism. Explore the experimental effects of intermittent hypoxemia and sleep fragmentation on lipolysis. 7/25/2014 7
Specific Aim 1: A cross sectional study will be performed to determine whether OSA is associated with an increase in adipose tissue lipolysis and decreased insulin sensitivity. Hypothesis: Severity of OSA as determined by the apnea hypopnea index (AHI) and degree of nocturnal hypoxemia will be associated with increased adipose tissue lipolysis (FFA levels) as well as reduced insulin sensitivity. 7/25/2014 8
Inclusion criteria: Community-based adults age > 21 years and 75 Ability to understand and consent to study procedures. Exclusion criteria: Previous or current use of PAP therapy or prior upper airway surgery for OSA History of diabetes mellitus Other sleep disorders (e.g., chronic insufficient sleep, narcolepsy) Use of immunosuppressive medications (e.g., steroids) in the past 30 days Significant medical or psychiatric comorbidities including but not limited to renal, cardiovascular, pulmonary, gastrointestinal, endocrine, depression, anxiety, schizophrenia, bipolar disorder. Epworth Sleepiness Scale (ESS) score 16 or work in transportation industry, or MVA (or near miss) from excessive sleepiness 7/25/2014 9
Phone Screening In person: H & P; informed consent Overnight sleep study Microdialysis and IVGTT 7/25/2014 10
OSA severity Apnea-hypopnea index (events/hr) Degree of nocturnal hypoxemia Polysomnogram 7/25/2014 11
Free Fatty Acids (FFAs) Microdialysis 7/25/2014 12
Insulin sensitivity Fasting Intravenous Glucose Tolerance Test (FIVGTT) 7/25/2014 13
Sample Size: To be determined, ancillary project to an NIH R01 study Multivariable linear regression: Model 1: Outcome: free fatty acids (FFAs) Predictors: age, gender, OSA severity, BMI, adipose tissue (DEXA scan) Model 2: Outcome: insulin sensitivity Predictors: age, gender, OSA severity, BMI, adipose tissue (DEXA scan) Model 3: Outcome: insulin sensitivity Predictors: age, gender, OSA severity, BMI, adipose tissue (DEXA scan), FFAs 7/25/2014 14
Specific Aim 2: A pilot study will be performed to determine if a) intermittent hypoxemia and b) sleep fragmentation are associated with increased lipolysis. Hypothesis: In normal healthy young adults, adipose tissue lipolysis will increase with intermittent hypoxemia and sleep fragmentation in a dose-dependent manner. 7/25/2014 15
Inclusion criteria: Young, community-based adults Age > 18 and 40 years No medical or psychiatric conditions. Ability to understand and consent to study procedures. Exclusion criteria: Any sleep disorder (e.g., chronic insufficient sleep, narcolepsy, obstructive sleep apnea, central sleep apnea or Cheyne-Stokes respiration on polysomnography) Use of immunosuppressive medications (e.g., steroids) in the past 30 days Significant medical or psychiatric comorbidities including but not limited to renal, cardiovascular, pulmonary, gastrointestinal, endocrine, major depressive disorder, anxiety, schizophrenia, bipolar disorder. Epworth Sleepiness Scale (ESS) score 16 or work in transportation industry, or MVA (or near miss) from excessive sleepiness 7/25/2014 16
Phone Screening In person: H & P; informed consent Overnight sleep study y Hypoxia Microdialysis Normoxia Microdialysis 7/25/2014 17
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Pilot study Collect preliminary data Assess feasibility of the study Sample Size: 5 Mean, standard deviation, and other descriptive statistics 7/25/2014 19
Both OSA and T2DM are prevalent and predispose to cardiovascular disease. There is an increased prevalence of OSA in T2DM as well as an increased prevalence of T2DM in OSA. Early identification of persons at high risk for either of these disorders may help reduce the risk of cardiovascular disease. Understanding mechanistic pathways may be important in developing targeted therapies to help reduce potential adverse outcomes. 7/25/2014 20
Group 4: Dr. Nae-Yuh Wang Dr. Susan Huftless Dr. Emilia Shin Dr. Neha Das Dr. Na You Qian Zhou Primary Mentor: Dr. Naresh Punjabi 7/25/2014 21
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