wk11_Buxton_lecture

wk11_Buxton_lecture - Sleep, sleep loss, sleep disorders,...

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Unformatted text preview: Sleep, sleep loss, sleep disorders, and metabolism Orfeu M. Buxton, Ph.D. Instructor in Medicine Division of Sleep Medicine Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts Seminar for Harvard undergraduate course MCB186, 11/16/2005 Objectives:What you might want to know about sleep Sleep/wake homeostasis and circadian rhythms affect sleep and wake patterns and endocrine function How much sleep does an individual need? Insufficient sleep can impair vigilance and performance alter energy balance and metabolism increase risk of obesity, diabetes, CVD, mortality 20 Sleep No sleep 20 15 10 5 0 10 05 04 03 02 01 10 25 20 15 10 5 14 18 22 02 06 10 0 10 20 15 10 5 0 10 14 18 22 02 06 10 14 18 22 02 06 10 14 18 22 02 06 10 Cortisol (g/ dl) Thyrotropin (U/ml) Prolactin (ng/ml) Growth Hormone (g/L) 15 10 5 0 10 05 04 03 02 01 10 25 20 15 10 5 0 10 20 15 10 5 0 10 14 18 22 02 06 10 14 18 22 02 06 10 acute sleep deprivation Buxton, Spiegel, and Van Cauter. Modulation of endocrine function and metabolism by sleep and sleep loss. In: Sleep Medicine, 2001. 14 18 22 02 06 10 14 18 22 02 06 10 Clock Time Melatonin: Circadian phase marker 180 135 Melatonin (pg/ml) 90 45 0 18 22 02 06 10 14 18 22 02 06 Clock time VanCauter et al. Amer J Physiol 1994. TSH: circadian control, sleep inhibition 4 TSH (mUI/ml) 3 2 1 18 22 02 06 10 14 18 22 02 06 10 14 18 22 Clock time (hour) Nocturnal sleep Nocturnal sleep deprivation Daytime recovery sleep Van Cauter & Aschoff, Endocrinology, DeGroot, ed, 1989. Cortisol: circadian control, sleep modulation 20 15 Cortisol (ng/ml) 10 5 0 18 22 02 06 10 14 18 22 02 06 10 14 18 22 Clock time (hour) Nocturnal sleep Nocturnal sleep deprivation Daytime recovery sleep Van Cauter et al., JCI, 1991. Cortisol: Sleep component 600 500 NORMAL SLEEP Mean Evening Cortisol Levels (nmol/L) 20 0 150 PLASMA 400 CORTISOL 300 (nmol/L) 200 100 0 ns 100 50 0 18 22 02 06 10 14 18 22 02 Day1 Day2 600 PARTIAL SLEEP DEPRIVATION 500 PLASMA 400 CORTISOL 300 (nmol/L) 200 100 0 200 150 100 p < 0.03 50 0 18 22 02 06 10 14 18 22 02 Day1 Day2 600 500 200 p = 0.003 150 TOTAL SLEEP DEPRIVATION PLASMA 400 CORTISOL 300 (nmol/L) 200 100 0 100 50 0 18 22 02 06 10 14 18 22 02 Day1 Day2 CLOCK TIME Day 1 Day 2 Day 3 Leproult et al, SLEEP, 1996. 54-hr profiles of glucose and insulin 130 120 Glucose (% mean) 110 100 90 80 18 160 140 22 02 06 10 14 18 22 02 06 10 14 18 22 Insulin Secretion Rate 120 100 (ISR, % mean) 80 60 18 22 02 06 10 14 18 22 02 06 10 14 18 22 Nocturnal sleep Nocturnal sleep deprivation Daytime recovery sleep Clock time (hour) How much sleep does an individual need? May depend on the activity/function or organ system being investigated Sleep duration an individual trait 7-9 hours the range for most people How much sleep do we "need"? Time in Bed: 8 hrs/night 14 hrs/night Conservation of photoperiod-responsive mechanisms in humans. Wehr TA, et al., Am J Physiol 1993: R846-R857 Sleep Dose Response: Mean Sleep Belenky et al, 2003 Mean Sleep Experimental Days 9 hr group 7.9 hrs 7 hr group 6.3 hrs 5 hr group 4.7 hrs 3 hr group 2.9 hrs Restricted sleep impairs vigilance Performance (% baseline) 110 100 90 80 70 60 50 40 0 T1 T2 B E1 E2 E3 E4 E5 E6 E7 R1 R2 R3 9 Hr 7 Hr 5 Hr 3 Hr 72 Hr TSD Baseline Sleep Restriction Recovery Belenky et al, JSR 2003 Day Chronic Sleep Loss: Overwork Longer workday: Since 1969, Americans have added 158 hours/year to workday. longer commute (census data). data 24-hour society: Shift work and night work. New York Times, 10 / 99 "Sleep debt" studies: impact on human health "Sleep Debt": chronic, partial sleep restriction Association of obesity and short sleep? Effects on neurobehavioral performance Broad endocrine impact Inducing a pre-diabetic state Prevalence of Overweight & Obesity US, 19992000 Overweight (but not obese) 34% Obese 30.5% Not overweight 34.5% Ogden et al, JAMA 2002 Perils of obesity 50% of morbidly obese have sleep disorder increased risk of diabetes Most diabetics have disturbed sleep Health care costs Personal & Family: Diabetes Cancer Early mortality Lower quality of life Significance of sleep for US obesity? 70 60 50 40 1960 1970 1980 1990 2000 9.0 8.5 Overweight and obese in the U.S. (%) mean sleep duration (hrs) 8.0 7.5 7.0 SOURCES Obesity: CDC (NHES, NHANES) Sleep: Roffwarg Science 1966, NHIS (unpublished data), National Sleep Foundation polls, Hale J Public Health 2005 6.5 1960 1970 1980 1990 year 2000 American Cancer Society: Association between BMI & Sleep Duration BMI (kg/m2) Women BMI (kg/m2) Men Hours of sleep Kripke et al, Arch Gen Psych, 2002 The Obstructed Upper Airway From: Quietsleep.com, Laurence I. Barsh, DMD Glucose intolerance, insulin resistance associated with SDB severity Glucose (mg/dL) Insulin (U/ml) Punjabi et al, 2002 Insulin Sensitivity in OSAS improved with CPAP & BMI<30 OSAS patients (compliant n=31) Euglycemic hyperinsulinemic clamp to estimate insulin sensitivity (Si) QuickTimeand a TIFF (LZW) decompressor are needed to see this picture. Post Si - Pre Si Harsch et al, AJRCCM (169) 2004 BMI (kg/m2) Cross-sectional evidence linking short sleep and metabolism Sleep Heart Health Study (SHHS), n>1100 Metabolism characterized by oral glucose tolerance test normal, impaired glucose tolerance, or type 2 diabetes Sleep and/or insomnia by self report Short sleep duration (<6 hrs night) with or without an insomnia-like symptom of difficulty sleeping relative to a 7-8 hour sleep duration, short sleep is associated with a significant increase in the Odds Ratio for a worsening of glucose tolerance Longitudinal evidence linking short sleep or insomnia and metabolism Nurses Health Study 10-year follow-up Self-reported short sleep duration (5 hours/night) RR (adjusted) 1.45 [1.08-1.92] of developing symptomatic diabetes Controlling for confounders such as BMI reduced the relative risk: sleep restriction may be an independent predictor for symptomatic diabetes, or may mediate its effect on diabetes via weight gain. Malm Preventative Project (Malm, Sweden) 15 year follow-up of non-diabetic healthy men Diabetes by questionnaire and/or fasting blood glucose levels Self report of "difficulties falling asleep" or regular hypnotic use OR of 1.52 [1.05-2.20] for development of diabetes Ayas NT et al. Arch Int Med 163 (2003) Nillson, PM et al. Diabetes Care 27:10 (2004) It's the naps you don't take that you regret the most Sleep Debt Study: Protocol BASELINE 8-h bedtime SLEEP DEBT 4-h bedtime M M M M M M Influenza vaccination M IVGTT M M M M SLEEP RECOVERY 12-h bedtime IVGTT M M M M M DAY B1 B2 B3 D1 D2 D3 D4 D5 D6 R1 R2 R3 R4 R5 R6 R7 09 09 13 17 21 01 05 CLOCK TIME Background: Intravenous Glucose Tolerance Test (IVGTT) GLUCOSE 250 (mg.dl-1) 150 50 INSULIN (pM) 600 400 200 0 -25 0 25 50 75 100 TIME (min) Parameters : Glucose Tolerance (Kg) 1st and 2nd Phase Insulin Secretion Insulin Sensitivity (Si)* Glucose Effectiveness (Sg)* * Calculated by Bergman's Minimal Model Glucose Injection at t = 0. Tolbutamide Injection at t = 20. Bergman, RN, Diabetes, 38 (1989), 1512-1527. Sleep Debt Study Results: IVGTT SLEEP DEBT 250 GLUCOSE (mg.dl-1) 150 50 600 INSULIN 400 (pM) 200 0 -25 0 25 50 75 100 -25 0 25 50 75 100 TIME (min) TIME (min) 3 2 1 0 %.min-1 %.min-1 p<0.04 SLEEP EXTENSION 3 2 1 0 p<0.01 pM.min p<0.03 10-5.min-1.pM-1 NS 400 200 0 10 5 0 GLUCOSE GLUCOSE ACUTE INSULIN INSULIN TOLERANCE EFFECTIVENESS RESPONSE SENSITIVITY Spiegel et al., Lancet, (1999) Sleep Debt Study results: Sleepiness, Sympatho-vagal Balance, Cortisol SLEEPINESS SYMPATHO-VAGAL BALANCE p<0.02 0.8 0.7 0.6 0.5 4 8 12 HOURS IN BED EVENING LEVELS OF FREE CORTISOL (nmol.L-1) (16:00-21:00) p<0.007 5.5 5.0 4.5 4.0 3.5 4 8 12 HOURS IN BED Spiegel et al., Lancet, (1999) S S S (10:00-14:00) 5 4 3 2 1 4 8 12 HOURS IN BED r R R (9:00-14:00) p=0.0001 Sleep Debt Study results: Thyrotropic Axis SLEEP DEBT 2.5 2.1 SLEEP EXTENSION TSH U/ml) ( 1.7 1.3 0.9 0.5 10.0 Free Thyroxine Index g/dl) ( 9.5 9.0 8.5 8.0 09 11 13 15 17 19 21 23 01 03 05 07 09 09 11 13 15 17 19 21 23 01 03 05 07 09 CLOCK TIME CLOCK TIME Reduced TSH levels and abolished circadian rhythm Spiegel et al., Lancet, (1999) A Sleep Debt impairs immune response to Influenza Vaccination 6 Mean Antibody Titers (10 ) p<0.03 1.50 1.25 1.00 0.75 0.50 0.25 0 0 10 21 to 31 NS NS Sleep Deprived, n=11 Control, n=14 Time relative to influenza vaccination (days) Spiegel et al., JAMA, 2002 A Sleep Debt signals a need to overeat, risks obesity 6.5 SLEEP 5.5 DEBT 6.5 SLEEP 5.5 EXTENSION 4.5 3.5 2.5 1.5 Leptin (ng/ml) 4.5 3.5 2.5 1.5 9 13 17 21 1 CLOCK TIME 5 9 9 13 17 21 1 CLOCK TIME 5 9 Spiegel et al., submitted Lower leptin levels signal negative energy balance Increased risk for overeating >>> obesity -Difference corresponds to underfeeding by 1000 Kcal for 3 days Chin-Chance et al., JCEM 2000 Sleep Duration is related to Leptin Taheri S et al., PLoS Medicine, 2004 Sleep Duration is related to ghrelin Taheri S et al., PLoS Medicine, 2004 Sleep Duration is related to BMI Taheri S et al., PLoS Medicine, 2004 Sleep loss >> negative energy balance Spiegel et al JCEM 2004 Short sleep may lead to overweight Laboratory-based study 3 leptin 2 (ng/ml) 1 0 4 hrs 10 hrs Epidemiology study 20 15 leptin (ng/ml)10 5 Mean age: 22 Mean BMI: 24 Mean age: 79 Mean BMI: 30 short sleep: leptin ghrelin 0 6 hrs 9 hrs 3 ghrelin 2 (ng/ml) 1 0 4 hrs 10 hrs 10 8 ghrelin 6 (ng/ml) 4 2 hunger BMI 0 5 hrs 8 hrs Spiegel et al Annals Internal Medicine 2004 Taheri et al., PLoS Medicine, 2004 Risks of short sleep and impact on human health Degraded neurobehavioral performance Broad endocrine impact Short-term: induces a pre-diabetic state Long-term risk: Obesity, Diabetes, CVD, mortality "Sleep Debt" Studies How much do you sleep? Do you get enough good sleep? New York Times, 01/1997 Sleep for balance ...
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This note was uploaded on 04/01/2008 for the course COGSCI 101 taught by Professor Buxton during the Spring '08 term at Rutgers.

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