Obstructive Sleep Apnea and Metabolic Health

Obesity is associated with numerous metabolic complications including Type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease (CVD) and several forms of cancer. However, the presence of these obesity-related metabolic abnormalities varies among obese individuals. The phenotype of a metabolically healthy obese (MHO) individual was initially described in 1980 and includes a subset of obese patients (as defined by BMI) who do not manifest the typical metabolic abnormalities associated with obesity. Although results are conflicting and highly dependent on patient population and diagnostic criteria for metabolic health, these individuals tend to have a preserved level of insulin sensitivity, absence of hypertension, and a more favorable lipid, inflammatory, hormonal, hepatic, and immunologic profile compared to the majority of metabolically abnormal obese (MAO) patients. This seeming paradox underscores that excess body the weight is not the sole determinant of obesity-related complications and allows for novel pathogenic investigation.

The postulated mechanism(s) underlying the differential metabolic profile in these individuals is not well known and the physiologic and molecular basis for 'healthy' obesity remains relatively undiscovered. In addition, a recent meta-analysis demonstrated that although MHO patients have a comparable metabolic profile to normal the weight individuals, their risk of adverse, long-term CV and mortality outcomes remains higher, calling into question the clinical importance of the healthy obese categorization. Despite these knowledge gaps, a limited number of studies have recently attempted to elucidate the processes that lead to the MHO profile, including characterization of lifestyle factors, adipocyte size, amount and location of ectopic fat, inflammatory mediators, and immune cells, and differences in gene expression.

The prevalence of obstructive sleep apnea (OSA) increases with increasing BMI and has also been linked to various cardiometabolic abnormalities. Patients with OSA experience repetitive episodes of hypoxia and reoxygenation during transient cessation of breathing that may provoke adverse systemic effects. These effects are reflected in increased levels of biomarkers linked to endocrine-metabolic and cardiovascular disease. OSA may exert negative effects on the cardiovascular system through multiple mechanisms including hypoxemia, sleep disruption, activation of the sympathetic nervous system, and inflammatory activation. In spite of this connection, the contribution of these deleterious effects in determining the phenotype of an obese patient (MHO vs. MAO) is unknown. Furthermore, the prevalence of OSA in these two subsets is not the well established.

In this study, the investigators hypothesize the prevalence of OSA is higher in MAO compared to BMI-matched MAO patients

Aim 1:

Define the prevalence of OSA in metabolically-healthy obese and metabolically abnormal obese (MHO and MAO) patients.

Aim 2:

Elucidate the association of OSA disease severity parameters with markers of clinically available abnormal metabolic profile (elevated cholesterol, blood pressure, fasting glucose/hemoglobin A1c, inflammatory markers, and insulin resistance if available).