Sleep Physiology and Metabolism

Chol Shin, MD, PhD, FCCP

chol-shin@korea.ac.kr

Sleep Disorder Center Department of Pulmonary and Critical Care Medicine

Korea University Medical Center

Normal Sleep

Changes of Sleep Structures with Age

Normal Metabolism with Normal sleep

Abnormal Metabolism during Sleep Disorders (sleep loss, SDB, etc.)

Conclusion

Outline

07 년 10 월 18 일

163Kg

치료전

07 년 10 월 18 일 08 년 03 월 03 일 08 년 06 월 11 일

120Kg 85Kg163Kg 83Kg

08 년 09 월 03 일

치료전 치료후

Korean University SDB clinic in 2014.Jan

Normal Sleep

Normal Sleep Architectures

REM :20-25%

NON REM : 75-80%Stage 1Stage 2Stage 3

From Kandel ER, Schwartz JH, Jessell TM, ed. Principles of Neural Science. 3rd ed. New York: McGraw-Hill; 1991:792-804.

Cycle of Human Sleep Stages

Control of Sleep-Wake State

Sleep-WakeHomeostasis

Process S

Circadian Rhythm

Process C

Sleep-Wake State

Changes of Sleep Structures with Age

16

12

14

6

10

8

24

4

2

01-15 3-5

14

11

10.58.5 7.75

76

5.75

13

12

2-36-23 5-93-5 19-3014-18 33-45 50 90

Neonate Infants Children Adolescents

Adults Old age

NREMsleep

REM sleep

Months YearsDays

Tota

l d

aily s

leep

(h

)

Changes of Sleep Structures with Age

Percentages of Sleep Period as a Function of Sleep

Cauter et al. JAMA 2000

Slow Wave SleepWake Time

REM Sleep

Stage 1 and 2 Sleep

16-25 26-35 36-50 51-60 61-70 71-8316-25 26-35 36-50 51-60 61-70 71-83

16-25 26-35 36-50 51-60 61-70 71-83

Metabolism during Normal Sleep

Leptin and Ghrelin; Normal Weight (Homeostasis)

Hunger and Appetite Hormones

VLPO and Orexin Neuron

SleepVLPO/GABA

Orexin systemLHA/PH

Cerebral cortex

Ascending arousal system

Ghrelin

Leptin

Sympathetic activity

+

++

+

PVN NTSNPY VTA/NA

↑Feeding Integration of peripheral signals of energy balance, appetite and

satiety

↑Waking

++++

+ +

-

-

-

Modified from Beccuti et al. Curr Opin Clin Nutr Metb Care 2011

NPY, neuropeptide Y; VTA, ventrotegmental area; NA, nucleus accumbens; PVN, paraventricular nucleus; NTS, nucleus tractus solitarius

Regulation of Feeding and Appetite by Sleep-Promoting VLPO Neuron

The Effect of Sleep Deprivation on (A) Leptin and Ghrelin Levels and (B) Hunger and Global Appetite

Ratings

(Sleep Medicine 9 Suppl. 1 (2008) Metabolic consequences of sleep and sleep loss)

Mean (SE) Values of Sleepiness, Sympathovagal Balance, and Saliva Cortisol Concentrations for All Three

Conditions

Spiegel K et al. LANCET 1999

4 8 12

4 8 12

Time in bed (h) Time in bed (h)

Sleepiness Evening cortisol

Sympathovagal balance

Abnormal Metabolism during Sleep Disorders

(sleep loss, SDB, Insomnia, etc.)

Sleep Loss

The World Health Organization (2004-2005) overweight: approx. 1.6 billion adults obese: 400 million diabetes: over 190 million death by CVD: 17.1 million

The National Health Interview Survey (Morbidity and Mortality Weekly Report 2005)

the percentage of adults sleeping ≤ 6 h: ↑5-6% between 1985 and 2004

Main causes of sleep loss a voluntary sleep curtailment pathological conditions such as insomnia and OSA a poor sleep hygiene

Increasing Number of Obesity and Sleep Loss

Cappuccio FP et al. Sleep 2008

Methods-634,511 participants (30,002 children and 604,509 adults)-children: 2-20 yrs, adults: 18-102 yrs

Results- pooled OR: 1.89 in children and 1.55 in adults

Forest Plots of the Associations Between Short Sleep Duration and Obesity (Children)

Pooled OR

Cappuccio FP et al. Sleep 2008

Forest Plots of the Associations Between Short Sleep Duration and Obesity (Adults)

Pooled OR

Cappuccio FP et al. Sleep 2008

U-Shape Association Among Sleep Duration, Chronic and Metabolic Diseases

Risk of Diseases

Sleep Duration (h)

7-8 h

Liu Y et al. SLEEP 2013

Association of Sleep Duration and Chronic Diseases

FMD: frequent mental distress

Vetrivelan R et al. Sleep 2012

- Objectives: To examine the consequences of chronic partial sleep loss on energy metabolism using rats with lesions in the VLPO

- Animals: VLPO-lesioned rats (30% loss of sleep)

- Conclusions: Chronic sleep loss did not lead to obesity or metabolic syndrome in rats

Other causes: Circadian disruption? Inactivity? Diet during the additional waking?

Short Sleep Habitual Sleep P value

Resting Metabolic Rate (RMR)

1455.4 ± 129.0 kcal/d 1486.5 ± 129.5 kcal/d 0.136

Total Energy Expenditure (TEE)

2589.2 ± 526.5 kcal/d 2611.1 ± 529.0 kcal/d 0.832

Energy and Nutrients Intake of Normal-Weight Men and Women During a Period of Short (<4h/night) or Habitual Sleep (>9h/night)

Resting Metabolic Rate and Total Energy Expenditure During a Period of Short or

Habitual Sleep

Marie-Pierre St-Onge et al. Am J Clin Nutr 2011

Patel et al. Obesity 2008

Potential Mechanisms by Sleep Loss May Predispose to Obesity

Sleep loss

Reduced or the same energy

expenditure

Obstructive Sleep Apnea

PurposeTo determine whether short sleep duration alone or combined with obstructive sleep apnea (OSA) is associated with regional body fat including abdominal visceral fat area (VFA) among Korean adults.

Methods-838 community participants aged 40-69 years old from the Korean Genome and Epidemiology Study-Subjective average sleep duration classified into five categories; < 5, 5~6, 6~7, 7~8, and ≥8 hours per day.-OSA : measured by overnight polysomnography (PSG) - Single slice CT scanning was used to quantify intra-abdominal adipose tissue

ConclusionsWe found that short sleep duration and OSA are both positively associated with regional body fat accumulation, and their combination has a synergistic effect onvisceral obesity. Kim NH and Chol Shin et al. Sleep 2013

Adjusted for age, sex, alcohol, smoking, exercise, the presence of diabetes mellitus, hypertension and cardiovascular disease, and BMI (Kim et al. SLEEP 2013)

Odds Ratios for Visceral Obesity according to Sleep Duration and Presence of OSA

Od

d R

ati

o

Sleep duration

PurposeTo investigate whether the impact of OSA on glucose metabolism is different according to the presence or absence of obesity

Methods-1,344 community participants aged >40 years from the Korean Genome and Epidemiology Study-Measurements: plasma glucose, HbA1c, insulin resistance-OSA : measured by overnight polysomnography (PSG) - Visceral obesity: abdominal computed tomography scanning

ConclusionsThe presence of OSA in non-obese individuals is significantly associated with impaired glucose metabolism.

Kim NH and Chol Shin et al. Diabetes Care 2013

Kim NH and Chol Shin et al. Diabetes Care 2013

Variables Associated with Glucose Metabolism According to Obesity and OSA Status After

Adjusting for Age, Sex, and BMI

IFG: impaired fasting glucoseIGT: impaired glucose tolerance

Association between OSA and Abnormal Glucose Metabolism According to Obesity

Status

Adjusted HbA1c Values for Patients According to OSA Severity

Aronsohn RS et al. Am J Respir Crit Care Med 2010

PurposeTo examine the association of habitual snoring with glucose and insulin metabolism in nonobese Korean men

Methods-2,719 men aged 40-69 years from the Korean Genome and Epidemiology Study-Habitual snoring: by a questionnaire, 4 days or more per week-Glucose and insulin revels: oral glucose tolerance test

ConclusionsHabitual snoring may affect glucose-insulin metabolism, independent of DM and hypertension, even in nonobese Korean men.

Chol Shin et al. Am J Respir Crit Care Med 2005

Glucose Insulin

Chol Shin et al. Am J Respir Crit Care Med 2005

Changes in Glucose and Insulin Levels during Oral Glucose Tolerance Tests

Glucose Metabolism in Mammalian Cells

Gatenby RA and Gillies RJ. Nature Reviews Cancer 2004

Pathways Linking Sleep Problem to Abnormal Glucose Metabolism and

Type 2 DM

Reutrakul S. Ann. N.Y. Acad. Sci 2014

Conclusion

혀

+

선순환고리

예방

악순환고리

중성지방 ↑ , chol 지방 ↑↑

증상같음

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