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Obstructive Sleep Apnea Endocrine effects. A. Valipour, MD, FCCP Department of Respiratory and Critical Care Medicine Otto-Wagner-Hospital Vienna. Prevalence: ~2-4% of population Risk Factors: Obesity Male Gender Anatomic Risk Factors Symptoms:
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Obstructive Sleep ApneaEndocrine effects A. Valipour, MD, FCCP Department of Respiratory and Critical Care Medicine Otto-Wagner-Hospital Vienna
Prevalence: ~2-4% of population • Risk Factors: • Obesity • Male Gender • Anatomic Risk Factors • Symptoms: • Excessive Sleepiness • Snoring/Apneas/Choking • Cognitive Dysfunction • Cardiovascular Morbidity and Mortality
OSA and Endocrinedisorders Spiegel K, Nature RevEndocrinol 2009
ObstructiveApnea: EndocrineEffects • Prevalence of endocrine/metabolic disease • Mechanism of action • Effects of treatment
ObstructiveApnea: EndocrineEffects • Prevalence of endocrine/metabolicdisease • Mechanism of action • Effects of treatment
Glucose- und Insulin levelsincreasewithseverity of OSA Punjabi NM et al., Am J Respir Crit Care Med 2002
Obesity + Hyperlipidemia + Hypertension + Impaired Glucose Tolerance ↓ Metabolic Syndrome Coughlin SR, EurHeart J 2004 Kono M et al., Chest 2007
Metabolic Syndrome „Z“ Parish JM, Chest 2009
ObstructiveApnea: EndocrineEffects • Prevalence of endocrine/metabolicfactors • Mechanism of action • Effects of treatment
ObstructiveApnea: Consequences Flow Sympathetic activation Intermittent Hypoxia Sleep fragmentation ↓ Endocrine Effects Apnea Apnea Thorax Abdomen SaO2
OSA: Mechanism of impairedglucosetolerance Punjabi NM et al., J ApplPhysiol 2005
Alteredglucosemetabolism as a consequence of sleepfragmentation Resultsfromintravenousglucose-tolerancetests in healthy individuals when fully rested and after sleepmanipulations Spiegel K, Nature RevEndocrinol 2009
Leptin: satietyhormoneGhrelin: appetite-stimulating hormone Spiegel K, Nature RevEndocrinol 2009
Intermittent hypoxia can cause acute insulin resistance in lean, healthy animals, and the response is associated with decreased glucose utilization of oxidative muscle fibers, but occurs independently of activation of the ANS Iiyori N, AJRCCM 2007
Intermittent hypoxia does not exacerbate pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity Li J et al., Circ Res 2005
12 male obeseleptin-deficientmice Standard diet 12 Weeks intermittent 5% FiO2 Upregulation of genes encoding: Cholesterol Fattyacidbiosynthesis Triglyceridesynthesis Sterolregualtorybindingelementprotein Li J et al., J ApplPhysiol 2005
FactorsassociatedwiththeMetabolic Syndrome: Clinicaldata Redline S et al., AJRCCM 2007
ObstructiveApnea: EndocrineEffects • Prevalence of endocrine/metabolic factors • Mechanism of action • Effects of treatment
All the lipids/lipoproteins improved significantly in patients with initial pathological levels. Börgel J, Eur Respir J 2006
At 12 weeks, improvement in Insulin Resistance was seen in subjects with BMI > 25sqm , but not in the subjects with BMI< 25 kg/sqm or the entire group. Lam JCM, EurRespir J 2010
CVD-Risk Score: sex, age, total cholesterol, HDL cholesterol, systolicbloodpressure, smoking and diabetes Dorkova Z, Chest 2008
Conclusions • High prevalence of metabolic syndrome in OSA • Mechanisms: • Intermittent Hypoxia • Sleep Fragmentation • CPAP treatment reduces metabolic/cardiovascular risk
Weightloss CPAP Chin K et al, Circulation 1999
Steatosishepatis in obesenon-OSA Steatosis and Inflammation in OSA Polotsky VY, AJRCCM 2008