Sleep and Obesity

1
Sleep and Obesity does the egg come before the
chicken?

• Francesco P Cappuccio MD MSc FRCP FFPH FAHA
• Cephalon Professor of Cardiovascular Medicine
  Epidemiology
• University of Warwick, Warwick Medical School,
  Coventry, UK

2
Historical background

• Steady decline in total sleep time during the
  past 100 years, generally attributed to lifestyle
  changes (increased shift work, longer working
  hours in less physically demanding jobs,
  increased and extended sedentary leisure time
  activities, ...)
• Parallel increase in the prevalence of overweight
  and obesity, particularly evident in the last 25
  years, also attributable to lifestyle changes
  (increased physical inactivity, energy intake, )
• Recent indication of a possible association
  between short sleep duration and obesity

3
BMI and Sleep Duration in US Adults Over Time
Is there a link between the growing obesity
epidemic and the decline in sleeping time?
Average Body Mass Index in US adults in the last
century
Average sleep duration (hours)in US adults in
the last century
4
Prevalence of overweight and obesity in children
and adults in the USA

Adults
Children
5
Mean sleep duration in healthy young adults
around the world
Steptoe A et al. Arch Int Med 20061661689-92
6
Sleep duration and self-rated health problems
Japan
Korea
Thailand
Taiwan
Steptoe A et al. Arch Int Med 20061661689-92
7
Short duration of sleep and all-cause mortality
Cappuccio FP et al. 2009 submitted
8
Obesity Epidemic and Sleep Duration Association
or Causation?
BMI in US adults
Sleep duration in US adults
9
Sleep duration and obesity in 6,862 children
(age 5-6 yrs)

von Kries R et al. Int J Obesity 200226710-6
10
Short duration of sleep and obesity in
children age 2 to 20 years
Sensitivity analysis from 1.61 (1.33 to 1.96) to
2.07 (1.54 to 2.79)
Cappuccio FP et al. Sleep 2008 31 619-26
11
Short Sleep Duration and BMI/ObesitySignificant
cross-sectional associations
BMI (kg/m2)
Odds Ratio Obesity
Stranges S et al. Am J Epidemiol. 2008 167 321-9
12
Short duration of sleep and obesity in adults age
15 to 102 years
Sensitivity analysis from 1.50 (1.39 to 1.61) to
1.59 (1.44 to 1.76)
Cappuccio FP et al. Sleep 2008 31 619-26
13
Prospective studies
Author (year) Country Sample size Age - Gender Study details Main findings
Hasler (2004) Switzerland 457 27 at baseline Men and women Prospective single age cohort F-up 13 y Less weight gain in those with longer sleep
Gangwish (2005) USA 3,208 32-49 at baseline Men and women Longitudinal population based (N-HANES) F-up 8-10 y Highest increase in BMI in those sleeping 2-4h pn
Biorkelund (2005) Sweden 498 38-60 at baseline Women Prospective population study F-up 32 y Short sleepers gained more weight that long sleepers
14
Short Sleep Duration and BMI/ObesityNo
prospective associations
BMI
OR Obesity
Stranges S et al. Am J Epidemiol. 2008 167 321-9
15
Possible Mechanisms
Appetite/satiety Leptin and Ghrelin Insulin
resistance/sensitivity Insulin,
Adiponectin Other hormonal mechanisms Cortisol,
SNS, Thyroid, GH Endothelial Function E-selectin,
Soluble intercellular adhesion molecules-
(sICAM-1) Inflammation/Immune system C-reactive
Protein (CRP), Interleukin 6 (IL-6), Tumor
necrosis factor ? (TNF-?), Fibrinogen
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Sleep and Metabolic functions
A U-shaped association between sleep duration and
BMI. Short sleep associated with low leptin and
high ghrelin
Leptin
BMI
Ghrelin
S Taheri et al. PLoS Med 20041(3)e62210-7
17
Sleep and Metabolic functions
Spiegel K et al. JCEM 2004895762-71
18
LACK OF SLEEP
Gale SM et al. J Nutr 2004134295-8
19
Vgontzas AN et al. J Int Med 200325432-44
20
Vgontzas AN et al. J Int Med 200325432-44
21
Sleep duration and Incidence of Diabetes
(1987-2004) in men, age 40-70 yrs, in
Massachusetts
Adjusted for multiple confounding
Yaggi HK et al. Diabetes Care 200629657-61
22
Short Sleep duration and Diabetes

• Elevation of evening cortisol levels predisposing
  to insulin resistance
• Increase in sympathetic tone, inhibiting
  pancreatic function and leading to increased
  glucose intolerance
• Weight gain and reduction in leptin
• Reduction of testosterone levels

23
Inflammation and Sleep

• Inflammatory markers are elevated in individuals
  undergoing short term sleep deprivation studies.
• Short sleep may lead to increased secretion of
  inflammatory cytokines, which in turn may lead to
  an increase in cardiovascular risk

Miller MA et al. Curr Vasc Pharmacol 2007
5(2)93-102.
24
Vgontzas AN et al. J Int Med 200325432-44
25
Vgontzas AN et al. J Int Med 200325432-44
26
Activation of the immune system and inflammatory
cytokines may affect sleep

• Many inflammatory responses are somnogenic
• However, in advance stages of inflammation the
  sleep promoting effects are diminished with the
  result of reduced NREM and increased wakefulness
• (Ann NY Acad Sci 2001933201-10)

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Bi-directional model of the sleep
deprivation-obesity association
Environment (work, social, physical)
Glucose intolerance/Insulin resistance Increased
appetite ( ? leptin ? ghrelin) More time to eat
? caloric intake
? energy expenditure
Increased fatigue Altered thermoregulation Activat
ion of inflammatory markers Sedentary extra time
Obesity
Short Sleep (Sleep deprivation)
28
Bi-directional model of the sleep
deprivation-obesity association
Environment (work, social, physical)
Glucose intolerance/Insulin resistance Increased
appetite ( ? leptin ? ghrelin) More time to eat
? caloric intake
? energy expenditure
Increased fatigue Altered thermoregulation Activat
ion of inflammatory markers Sedentary extra time
Obesity
Short Sleep (Sleep deprivation)
Sleep disordered breathing Disrupted and short
sleep Inflammatory cytokines and the brain
29
Conclusions

• The epidemic of obesity is paralleled by a
  silent epidemic of reduced sleep duration.
• These trends are detectable in adults as well as
  in children as young as 5 years.
• Short sleep duration is associated with increased
  risk of obesity both in adults and in children.
• Evidence from prospective studies does not always
  confirm a temporal sequence
• A plausible mechanism could be the effect of
  short sleep on appetite through the
  ghrelin-leptin system
• Bi-directional effects (obesity causes lack of
  sleep) might also explain the association
• More research needed to understand the mechanisms
  by which short sleep is linked to chronic
  conditions of affluent societies, such as
  obesity, diabetes and hypertension.

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SLEEP, HEALTH SOCIETY University of Warwick,
Warwick Medical School sleepresearch_at_warwick.ac.uk
Leads FP Cappuccio MA Miller Warwick
Team E Peile, O Franco, S Stranges, N-B
Kandala, FM Taggart, C Ji, G Ward, A
Bakewell, A Currie, A Lowe, D Cooper Collaborators
Warwick S Williams, D Banejee R.C.P. R
Pounder U.C.L. MG Marmot, E Brunner, M Kumari,
M Shipley, JE Ferrie, M Kivimaki Surrey D-J
Djik, S Archer Boston (Harvard) C Czeisler,
SW Lockley, CP Landrigan, JP Sullivan Naples
(Federico II) P Strazzullo Avellino (CNR) G
Barba Buffalo (SUNY) J Dorn, R Donhaue, M
Trevisan Funding Cephalon Inc., Wingate
Foundation, Whitehall II, RDF University of
Warwick, NHS Workforce