Presenter Disclosure Gary D. Foster, PhD Obesity, Weight Loss and - PowerPoint PPT Presentation

Presenter Disclosure Gary D. Foster, PhD Obesity, Weight Loss and OSA Scientific Advisory Board/Advisory Panel: • Nutrisystem, ConAgra Foods, Tate and Lyle, United Health Group Gary D. Foster, Ph.D. Consultant: Chief Scientific Officer, Weight Watchers • Eisai, Medtronic, GSK, Food Service Corporation International Adjunct Professor of Medicine, Public Health & Research Support: Psychology • NIH, USDA, CDC, Robert Wood Johnson Foundation, Coca-Cola Founder and Emeritus Director, Center for Company, Nutrisystem, American Beverage Association, Novo Nordisk Obesity Research and Education Employee/Shareholder: Temple University School of Medicine Weight Watchers International Prevalence of Overweight and Obesity Among Overview US Adults Overweight (BMI ≥ 25) Obesity (BMI ≥ 30) • Obesity and OSA • Weight Loss and OSA • Treatment of Obesity – Behavioral Treatment – Dietary Treatment – Pharmacological Treatment – Patient Expectations Flegal, K et al. JAMA, 2002; Hedley, AA et al. JAMA, 2004;Ogden et al JAMA,2006, Flegal et al. JAMA, 2010

Medical Complications of Obesity Obesity and OSA Idiopathic intracranial Pulmonary disease hypertension • Two-thirds of OSA participants are obese 1 abnormal function Stroke obstructive sleep apnea hypoventilation syndrome Cataracts Nonalcoholic fatty liver Coronary heart disease • One SD increase in BMI is associated with disease Diabetes steatosis a 4-fold increase in AHI 2 Dyslipidemia steatohepatitis Hypertension cirrhosis Severe pancreatitis Gall bladder disease • 40% of weight-loss patients have RDI>5 3,4 Cancer Gynecologic abnormalities breast, uterus, cervix abnormal menses colon, esophagus, pancreas infertility kidney, prostate polycystic ovarian syndrome Osteoarthritis Phlebitis Skin venous stasis 1 Guilleminault C. et al, Chest, 1998 2 Young T. et al, NEJM, 1993 Gout 3 Richman R. et al, IJO, 1994 4 Vgontzas A. et al, Arch Intern Med, 1994 Interactions between OSA, obesity, sleep Weight Loss and OSA deprivation & metabolic abnormalities • Weight losses of 9% to 20% have been associated with reductions in AHI of 30% to 74% 1 • A 1% change in weight is associated with a 3% change in AHI 2 – 10% ↓ in weight is associated with a 26% ↓ in AHI – 10% ↑ in weight is associated with a 32% ↑ in AHI1 1 Strobel RJ & Rosen RC., Sleep, 1996 2 Peppard et al., JAMA, 2000 Romero-Corral A. et al., Chest, 2010

Relationship between change in AHI and change in Weight Loss and AHI BMI during a mean period of 5 years n=160, at Baseline Mean BMI 29.3 ± 4.7 kg/m 2 , Mean AHI 23.0 ± 22.6 • Until 2009, no RCT had assessed the effects of events/h weight loss on OSA • Among weight-loss treated (n=15) and control (n=8) patients, a 9% weight loss was associated with 47% reduction in AHI • Across uncontrolled studies, there was no r 2 = 0.258 significant relationship between weight loss and p<0.001 the change in AHI Berger G et al., Eur Respir J, 2009 Effect of a very low energy diet on moderate and severe OSA in Changes in Weight and AHI at 9 weeks obese men: a randomized controlled trial • Sample description 20 – 63 obese men 10 – Age = 49 ± 7.3 y 0 – Weight = 112.5 ± 14.2 kg Change -10 – AHI = 37 ± 15 events/h Control Intervention – BMI ≈ 34.6 kg/m 2 -20 • Randomly assigned to 1 of 2 conditions -30 – A liquid very low energy diet (2.3 MJ/day, 549.3 -40 kcal/day) for 7 weeks to promote weight loss, followed by 2 weeks of gradual introduction of normal foods. -50 Weight (kg) AHI (events/h) – The control group adhered to their usual diet. [Data represent mean changes with standard deviation (SD)] – 9 week study Johansson et al., BMJ, 2009 Johansson et al., BMJ, 2009

Improvement in OSA at week 9 Changes in Weight and AHI at 1 yr • Proportions of patients 20 defined as having no (cured), mild, moderate, or severe 10 obstructive sleep apnea at week 9 0 Change -10 • Proportions of patients who 9 weeks improved, maintained, or -20 1 year worsened their obstructive sleep apnea status after 9 -30 weeks -40 • Error bars are 95% CIs. -50 Weight (kg) AHI (events/hr) P< 0.001 for both Johansson et al., BMJ, 2009 Johansson et al., BMJ, 2011 Changes in Weight and AHI at 1 yr Lifestyle intervention with weight reduction: (n=72) First-line treatment in mild OSA 10.0 • Sample Description 5.0 – 72 (53 males, 19 females) patients with mild OSA – Age = 51.3 ± 8.8 y 0.0 – Weight = 96.8 ± 11.6 kg Change Control -5.0 – AHI= 9.65 ± 3.0 events/h Intervention – BMI= 32.4 ± 2.7 -10.0 • Randomly assigned to 1 of 2 conditions -15.0 – A 12 week VLCD (600-800 kcal/day) program with -20.0 supervised lifestyle modification Weight (kg) AHI (total) – Routine lifestyle counseling [Data represent mean changes with standard deviation (SD)] – Duration was 1 year The odds ratio for having mild OSA at 1 y was 27% lower in the intervention group Tuomilehto HP et al., Am J Respir Crit Care Med 2009 Tuomilehto HP et al., Am J Respir Crit Care Med 2009

Change in Weight and AHI at 1 yr Remission of mild OSA at 1 yr 100 90 Remission of mild OSA (%) 80 70 60 50 40 30 -5kg -2.0 20 events/h 10 0 - - > 15kg - 15 to 5 kg - 5 to 0 kg > 0 kg Weight change from baseline to 12 month follow-up Tuomilehto HP et al., Am J Respir Crit Care Med 2009 Tuomilehto HP et al., Am J Respir Crit Care Med 2009 Sustained improvements of OSA by lifestyle changes at 2 yr follow-up (n=71, 99%) Sleep AHEAD: Sleep Apnea in Look AHEAD Participants Sleep AHEAD Action for Health in Diabetes - - - - Sleep AHEAD supported by NIH NHLBI grant HL070301 Vertical bars indicate 95% CIs. Look AHEAD supported by NIH NIDDK grants DK57135, DK57002, DK56992, Tuomilehto HP et al., Am J Clin Nutr, 2010 and DK57178

Sleep AHEAD Inclusion/Exclusion Criteria Providence Pittsburgh Inclusion Criteria • Score on a questionnaire designed to identify individuals at increased risk of OSA PSGRL Exclusion Criteria • Patients currently being treated for OSA (e.g., CPAP, oral appliance) • Participants who had prior surgical treatment for OSA Philadelphia New York City Columbia Overnight polysomnograms were performed in the Polysomnogram Scoring Criteria participants’ homes The following signals are recorded on a data • Apnea acquisition system (Compumedics PS2): – cessation of airflow for ≥ 10 sec – Electroencephalogram (C3A2, C4A1) – Bilateral electrooculograms (A2 & A1, respectively) • Hypopnea – Bipolar submental electromyogram – At least a 30% reduction in chest wall – Movements of the rib cage and abdomen movement or airflow lasting at least 10 – Nasal pressure as an index of airflow seconds with ≥ 4% oxygen desaturation – Body position • Apnea-Hypopnea Index (AHI) – Pulse oximetry – the mean number of apneas and hypopneas – Electrocardiogram per hour of sleep – Presence or absence of snoring

Sleep Ahead Participants Sleep AHEAD Measures (N=305) Variable Mean ± SD Baseline, 1, 2, and 4 years: Race/ethnicity (%) White 73.0 • Apnea-hypopnea index African American 19.1 Other 7.9 • Body weight Postmenopause (%) 90.1 • Waist circumference Age (years) 61.3 ± 6.5 • Neck circumference BMI (kg/m 2 ) 36.5 ± 5.8 Weight (kg) 101.7 ± 18.0 Height (cm) 167.0 ± 9.7 No difference between DSE and ILI groups Foster et al., Diabetes Care, 2009 Sleep Ahead Participants (N=305) Variable Mean ± SD Waist Circumference (cm) 115.0 ± 13.0 Neck Circumference (cm) 41.1 ± 4.4 Baseline Prevalence Obstructive apnea index 11.1 ± 12.8 Central apnea index 0.4 ± 1.0 of OSA Hypopneas w/ ≥ 4% oxygen desaturation Apnea-hypopnea index 20.5 ± 16.8 Hypopnea index 9.0 ± 8.1 Oxygen desaturation index 17.6 ± 14.7 ( ≥ 4%) Epworth Sleepiness Score 7.9 ± 4.6 No difference between DSE and ILI groups Foster et al., Diabetes Care, 2009

Sleep Disordered Breathing in Obese Undiagnosed, Unscreened Sleep Disordered Breathing in Obese Patients with Type 2 Diabetes (N=202) Patients with Type 2 Diabetes (N=305) 13.4% No 12.4% No OSA OSA 22.6% 22.3% Severe Severe AHI < 5 AHI < 5 AHI 5-14.9 AHI 5-14.9 AHI 15-29.9 AHI 15-29.9 AHI > 30 AHI > 30 33.5 % 32.2 % Mild Mild 30.5% 33.1% Moderate Moderate Foster et al., Diabetes Care, 2009 Foster et al., Diabetes Care, 2009 Risk Factors for Presence of OSA • Waist circumference (OR=1.1;95% CI: 1.0-1.1; p<.05) One-Year Results – A 1 cm increase in waist circumference was associated with an increase of 10% in the predicted odds of the presence of OSA (AHI>5) • No other measured variables, including symptoms, predicted the presence of OSA Foster et al., Diabetes Care, 2009