Sleep Apnea Karoline Moon, MD, MSPH Fellow, Division of Pulmonary - PowerPoint PPT Presentation

The Role of Glucagon in Obstructive Sleep Apnea Karoline Moon, MD, MSPH Fellow, Division of Pulmonary Medicine Department of Medicine JHU School of Medicine July 25, 2014

Background • Obstructive sleep apnea – Characterized by intermittent hypoxia – Associated with diabetes and dysglycemia independent of obesity • Intermittent hypoxia associated with higher fasting glucose in animal and healthy human studies • Hepatic glucose output controls fasting glucose and is regulated by multiple factors including: – glucagon, catecholamines, insulin, and free fatty acids • Catecholamines are known to be elevated in OSA • Whether glucagon levels are higher in persons with vs. those without OSA is unknown

Conceptual Model Obstructive Sleep Apnea Intermittent Hypoxia  Systemic Inflammation  Sympathetic Nervous  Adipo-Cytokines System Activity  Oxidative Stress Type 2 Diabetes

Glucagon and Fasting Glucose Low Blood Sugar Glucagon Liver Hepatic Glucose Output Raises Blood Sugar

Hypotheses • Fasting glucagon is higher in patients with vs. those without OSA • Fasting glucagon accounts for some of the elevation in fasting glucose observed in patients with OSA

Study Population • Cross sectional study • Males, 65 years or older recruited as part of larger trial of osteoporosis (MrOS Sleep Study) • Plasma samples from 118 participants available at Johns Hopkins • Exclusions: Patients with history of diabetes or incomplete overnight polysomnography (PSG)

Enrollment from 6 US clinical centers (n=3,135) Standardized Polysomnogram Protocol + Fasting blood sample morning after PSG, plasma separated and stored at -80°C (n=2,604) emerysleepcenter.com Plasma samples available at Johns Hopkins (n=118) Exclude samples with history of diabetes Measure glucagon levels with commercially available kit (Millipore Glucagon ELISA)

Analysis • Primary dependent variable: fasting plasma glucagon • Secondary dependent variable: fasting plasma glucose • Independent variables (separate models): – OSA status – Severity of OSA by Apnea-Hypopnea Index (AHI) – Metrics of hypoxic stress: average oxygen saturation during sleep, frequency of oxygen desaturation, proportion of sleep time below oxygen saturation 90% • Separate multivariable generalized linear models (GLM) for glucagon and fasting glucose to determine association with OSA and its severity • Multivariate GLM for glucagon with fasting glucose as an independent variable (mediation analysis) • Covariate adjustment for age, race, BMI

Significance • We expect that worsening OSA will be associated with increases in both fasting glucose and glucagon levels • If glucagon levels are elevated in OSA, glucagon signaling may be a potential therapeutic target • Lack of an association of glucagon levels with OSA would suggest that other mechanisms for derangement of fasting glucose in OSA should continue to be explored

Questions?