Sleep from the Inside Out

Sleep from the Inside Out
Disclaimer
Appendix 3 Declaration of Vested Interest Form
Name of presenter: Heather Murgatroyd , RRT, RPSGT
Name of employer: DeVilbiss Healthcare
Definition: A presenter may have an interest in or affiliation with an organization, which does not prevent him or her from
making a presentation, however, the audience must be informed of this relationship before the presentation of the activity. For
this purpose a real or apparent conflict of interest is defined as having a significant financial interest in a product to be
discussed directly or indirectly during the presentation; being or having been an employee of a company with such financial
interest and/or having had substantial research support by an industry to study the product to be discussed at the presentation.
I recognize that I must follow all guidelines and criteria regarding vested interest.
[ ] No, I have no real or perceived conflicts of interests that relate to this presentation. (If the response is no, stop here.)
[ x ] Yes, I have the following real or perceived conflicts of interest that relate to this presentation:
Describe real or perceived conflicts of interest that relate to this presentation
I am an employee of DeVilbiss Healthcare and we manufacture respiratory home care equipment.
My presentations are not product specific but relate to the principles involved in best utilizing certain
technologies in the home environment.
Objectives
• Define diabetes and how to diagnose. Discuss
diabetes and related conditions in relation to
Sleep Disordered Breathing.
• Define Inflammation and the various markers
as related to Sleep Disordered Breathing.
• Identify various hormones, their functions,
abnormalities and how they relate to Sleep
Disordered Breathing.
What is Diabetes?
A group of diseases marked by high blood
glucose
•
Type 1 – (previously called juvenile
diabetes) the body does not produce
insulin, the immune system destroys
the cells in the pancreas that produce
insulin, typically diagnosed in
childhood or young adulthood, 5% of
all diagnosed diabetes, no known
prevention
•
Type 2 – most common type, 90-95% of
cases, body does not produce enough
insulin or does not utilize the insulin
produced
•
Gestational – occurs during pregnancy
when a non-diabetic woman develops
high blood sugar levels, 2-10% of
pregnancies
http://www.cdc.gov/diabetes/pubs
http://www.diabetes.org/diabetes-basics
Important Terms
•
•
•
•
Insulin - a hormone that helps the body
use glucose for energy. The beta cells
of the pancreas make insulin. People
with Type 1 diabetes must take insulin
via injection or pump.
Glucose - one of the simplest forms of
sugar.
Blood Glucose - the main sugar found
in the blood and the body's main
source of energy. Also called blood
sugar.
A1c – measures average blood glucose
for past 2-3 months. Glucose binds to
hemoglobin and the amount is
proportional to the amount of glucose
in the blood. Normal is about 5%.
Measuring A1c shows history of blood
sugar control. Poorly controlled may
show 15% or higher.
http://www.diabetes.org/diabetes-basics
Type 2 Diabetes
Symptoms –
•
•
•
•
•
•
•
•
•
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Frequent urination
Unusual thirst
Extreme hunger
Unusual weight loss
Extreme fatigue and Irritability
Frequent infections
Blurred vision
Cuts/bruises that are slow to
heal
Tingling/numbness in the
hands/feet
Recurring skin, gum, or bladder
infections
http://www.diabetes.org/diabetes-basics
Diagnosing Type 2 Diabetes
A1c – blood draw, detects Type 2 and prediabetes, does not require fasting –
can be done anytime
Fasting plasma glucose test – blood draw,
detects diabetes and pre-diabetes,
must fast 8 hours prior, most reliable if
done in a.m.,
Oral glucose tolerance test – detects
diabetes, pre and gestational,
sensitive, must fast 8 hours then drink
75g of glucose dissolved in water and
fast an additional 2 hours
Random plasma glucose test – blood draw
from non-fasting person, values are
higher due to assumed meal
All tests are not done but a second test
must be done to confirm if there are
not additional clear symptoms of
diabetes
Diabetes Care. 2012;35(Supp 1):S12
Complications of Diabetes
•
•
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High blood pressure
Heart Disease
Stroke
Blindness
Kidney disease
Neuropathy
Amputation
Dental disease
Depression
http://www.diabetes.org/diabetes-basics
http://www.cdc.gov/diabetes/pubs
Cost of Diabetes for 2012 (updated 3/13)
• $245 billion: Total costs of diagnosed diabetes in
the United States in 2012
• $176 billion for direct medical costs
• $69 billion for indirect costs (disability, work loss,
premature mortality)
http://www.diabetes.org/diabetes-basics
Adults 18 years and older
• 45-64 age group – 118% increase of diabetes
diagnosis – 5.5% to 12.0%
Source: 2007–2009 National Health Interview Survey estimates projected to the year 2010.
Diabetes is a big deal (2010)
•
There are 25.8 million people in the
United States, or 8.3% of the
population, who have diabetes.
•
Medical expenses are 2 times higher
for people with diabetes then for
people without.
•
Diabetes is the 7th leading cause of
death in the United States
•
A person with diabetes is about twice
more likely to die then someone else
the same age without diabetes.
http://www.diabetes.org/diabetes-basics
http://www.cdc.gov/diabetes/pubs
• We work in Sleep and Respiratory…
• Why are we talking about this?
Glucose Metabolism
• There is an established association between
altered glucose metabolism and SDB
• What is the mechanism?
- Increased sympathetic nervous system activity resulting
from intermittent hypoxia, sleep fragmentation and sleep
loss – the body releases glucose but does not properly
clear it and does not release proper insulin to process.
http://journal.publications.chestnet.org/article.aspx?articleid=1085691
• Hypoxemia has been shown to impair glucose
metabolism
• As the severity of SDB increases there is an
association to poor glucose control
• Reduced slow wave sleep is associated with
poor glucose control
• In patients who participated in voluntary sleep
deprivation studies, it was shown that is an
association between abnormal glucose
tolerance and sleep deprivation
http://www.journalsleep.org/ViewAbstract.aspx?pid=28399
Insulin Resistance
• Maybe part of the Metabolic
Syndrome (commonly
present)
• Precedes T2DM
• Condition in which the cells
become resistant to a given
amount of insulin
• More insulin is needed for
proper effects
• Pancreas produces more to
meet the body’s demand and
eventually cannot produce
enough
http://www.medicinenet.com/insulin_resistance/article.htm
Islets of Langerhans in the pancreas,
where insulin is produced
Insulin Resistance and CPAP
•
Sleep deprivation results in insulin resistance in
healthy subjects – which resolves after
recovery sleep*
•
Several studies show treatment with CPAP
improves insulin resistance
Weinstock et al. studied 50 patients with impaired glucose tolerance
and moderate-severe OSA. Results showed participants with severe
OSA (> 30/h) had improvement of insulin sensitivity tests after 2 months
vs. those receiving sham CPAP. However, improvement was not as
significant with less severe OSA patients.
Sharma et al. studied 86 patients, (75 with metabolic syndrome) with
moderate-severe OSA on CPAP for 3 months and showed a reduction
in HbA1C vs those receiving sham CPAP.
*SLEEP, Vol. 35, No. 5, 2012
Metabolic Syndrome (aka Syndrome X)
• Group of risk factors that occur
together
• May increase risk of T2DM
and coronary artery disease
and stroke
• Risk factors:
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Central obesity
Insulin resistance
aging
Lack of exercise
genetics
Hormone changes
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004546/
Metabolic Syndrome
Having 3 or more of the following:
•
•
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Blood pressure 130/85 mmHg or
higher
Fasting blood sugar/glucose 100
mg/dl or higher
Waist circumference of
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Low HDL cholesterol
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•
40 + inches for men
35 + inches for women
Under 40 mg/dl for men
Under 50 mg/dl for women
Triglycerides of 150 mg/dl or higher
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH000454
Metabolic Syndrome and SDB
• Some discussion of adding OSA to the features of
Metabolic Syndrome and calling it “Syndrome Z”
• Metabolic Syndrome and OSA have multiple
overlapping characteristics
• A study by the National Cholesterol Education
Program identified in the Adult Treatment Panel III
report that Metabolic Syndrome is approximately
40% greater in patients diagnosed with OSA
Kostoglou-Athanassiou and Athanassiou. Metabolic syndrome and sleep apnea. 2008.
• Sleep disordered breathing may influence the sympathetic
nervous system and catecholemine release which may
stimulate gluconeogenesis leading to hyperinsulinemia
WHAT??!!
• When a person has SDB causing arousals, this triggers
the “fight or flight” response, which in turn stimulates new
glucose production and release causing increased insulin
in blood.
What can Hyperinsulinemia cause?
• High triglycerides (increased risk of heart and stroke)
• High plasminogen activator inhibitor activity (PAI-Fx),
causing increased risk of clotting
• Low HDL cholesterol (increased risk of heart attack and
stroke)
• High uric acid (gout)
• Polycystic ovary syndrome (endocrine disorder with oligoamenorrhea, infertility, hirsutism, obesity, high Leptin
levels)
• Type 2 diabetes
• Obesity
• High insulin can also stimulate the kidney to produce
angiotension, a substance which increases blood
pressure
http://www.jewishhospitalcincinnati.com/cholesterol/Research/insulin_resistance.html
Diabetes & Sleep Disordered Breathing
• Five studies – found 58% - 86% obese diabetic
patients also have OSA
• Increase severity of OSA associated with increased
A1c levels*
• Habitual snoring males, whether or not obese, are
at greater risk of developing Type 2 Diabetes as
compared to non-obese males without habitual
snoring or obese males without habitual snoring**
*http://www.frontiersin.org/Sleep_and_Chronobiology/10.3389/fneur.2012.00126/full
**The role of habitual snoring and obesity in the development of diabetes: a 10-year
follow-up study in a male population. Journal of Internal Medicine, 2000;248:13-20
Diabetes & Sleep Disordered Breathing
In the Sleep Heart Health Study
looking at diabetic participants (DP)
vs. non-diabetic participants (NDP),
Diabetic participants were
observed to have:
•
•
•
•
Higher overall RDI
Lower O2 levels
Less time in NREM 3
More time in NREM 1 and 2
Data from the SHHS continues to
support the relationship of obesity
with both SDB and T2DM. The
importance of addressing obesity
for patients with either condition is
important in the role SDB plays in
the exacerbation of cardiovascular
disease.
Diabetes Care, Vol 26, No 3, March 2003.
Diabetes & Sleep Disordered Breathing
•
In children (5-11) with Type 1
diabetes a study showed more
frequent and longer apneas,
particularly centrals, when
compared to children without
T1DM
•
Youths with diabetes spent less
time in N3 and longer periods in
N2 then youths without diabetes
•
PTs with poorly controlled
diabetes were shown to have
more frequent and longer apneas
then those with well controlled
diabetes and control subjects
Does CPAP help?
•
Limited research on how treating SDB
improves insulin sensitivity and no
research on how treating SDB for the
prevention of T2DM
•
Does treatment of OSA help prevent, delay,
slow the progression, reduce the severity
of Type 2 diabetes, or improve impaired
glucose tolerance (also called “prediabetes”)?
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‒
For patients with mild/moderate sleep apnea and
obesity – NO
For patients with severe sleep apnea YES
There are mixed results from studies as they have
typically been small studies and done with limited controls
A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance
and Sleep Apnea. Sleep, Vol. 35, No. 5, 2012
Does CPAP help?
“Amongst diabetics with sleep breathing disorders, improvement
of insulin responsiveness or glycaemia during continuous
positive airway pressure (CPAP) treatment has been reported
even without a significant change of obesity.”
CHEST. 2008;133(2):496-506. doi:10.1378/chest.07-0828
Does CPAP help?
Studies show –
• Harsch et al. - CPAP on non-diabetic
patients improved insulin sensitivity index as
quickly as 2 days after start of treatment.
• Babu et al. - Reductions in HbA1c almost
immediately in patients with abnormally high
baselines once on CPAP. Also showed
patients with >4 hour/day compliance had
reductions in HbA1c which correlated with
hours of CPAP use.
Levy,P. Bonsignre, MR and J. Eckel. Sleep, sleep-disordered breathing and metabolic
consequences. European Respiratory Journal. Vol. 34, No 1. 2009.
Does CPAP help?
• Lindberg et al. showed reductions in fasting insulin
levels and insulin resistance after 3 weeks of CPAP
therapy when compared to matched controls not
using CPAP.
• Weinstock et al. showed that for severe OSA
patients (AHI >30/h) active use of CPAP improved
insulin sensitivity index from baselines.
http://journal.publications.chestnet.org/article.aspx?articleid=1085691
CPAP Therapy and Glucose Control in Sleep Apnea—Weinstock et al
SLEEP, Vol. 35, No. 5, 2012.
Does CPAP help?
Due to conflicting study
reports regarding the benefits
of CPAP on T2DM, glucose
metabolism, insulin
resistance, Metabolic
Syndrome It is important to know how
studies are being conducted.
Does CPAP help?
Challenges for many of the studies–
• Small sample sizes
• Limited durations
• Obesity role in both T2DM and
OSA
• Conflicting study results may
support that CPAP has a
positive effect on some, not all,
components of IR, Syndrome X,
glucose metabolism
Diabetes and sleep deprivation
•
•
•
Slow Wave Sleep deprivation
also effects glucose tolerance
and insulin resistance.
In healthy subjects with
normal total sleep time but
reduced slow wave sleep
resulted in decreased insulin
sensitivity. There should be
an increase in insulin release
to compensate, yet this was
not seen.
As we age, we spend less time
in SWS. Could this possibly
contribute to the development
of T2DM in the elderly?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242689/
Inflammation:
• Is the body’s response to
a harmful stimuli, the
means of removing it and
start the healing process
• Can be acute or chronic
• Acute inflammation
begins immediately upon
injury, lasts a few days
and either resolves or
becomes…
Chronic Inflammation
• May last months or years
• Is destructive, resulting in
tissue damage, fibrosis and
necrosis
• Many disorders considered to
have an inflammatory
process: arthritis, acne,
sarcoidosis, asthma, colitis
• “itis” = inflammation
http://en.wikipedia.org/wiki/Inflamation
Obesity, OSA and Inflammation
• Obesity along with OSA is a
strong determinant of
systemic inflammation.
• Many adipokines (cell
messengers) are released by
adipose tissue and are linked
to inflammation. Obesity
increases their production =
increased inflammation.
• There are synergistic negative
effects of OSA and obesity
regarding inflammation – more
research is needed.
Levy,P. Bonsignre, MR and J. Eckel. Sleep, sleep-disordered
breathing and metabolic consequences. European
Respiratory Journal. Vol. 34, No 1. 2009.
Inflammation and OSA
• Repetitive hypoxia and re-oxygenation leads to oxidative
stress
• Oxidative stress is an imbalance which prevents cells from
communicating properly. This affects basic functions such
as tissue repair and immunity and may result in the
development of diseases such as cancer and diabetes.
Levy,P. Bonsignre, MR and J. Eckel. Sleep, sleep-disordered breathing and metabolic consequences.
European Respiratory Journal. Vol. 34, No 1. 2009.
Oxidative Stress and OSA
Oxidative Stress is reported to be linked to:
• Neurodegenerative diseases
• Cardiac diseases
• Age-related cancer development
• Contribute to aging
How is OSA a factor? The repetitive reoxygenation after apneic events may cause a
cascade of cell dysfunction contributing to
oxidative stress.
SLEEP, Vol. 30, No. 3, 2007
• Hypoxia in adipose tissue may cause an inflammatory
response - the release of inflammatory adipokines
• Growing evidence that hypoxia plays a strong role in
gene response and function.
Obesity + SDB + Hypoxia = CHRONIC INFLAMMATION
Levy,P. Bonsignre, MR and J. Eckel. Sleep, sleep-disordered breathing and metabolic
consequences. European Respiratory Journal. Vol. 34, No 1. 2009.
Markers of Inflammation
• C-reactive protein (CRP) is a biomarker of any
inflammation – CPAP has successfully decreased Creactive levels in OSA patients, but did not change in
non-obese OSA patients
• Short bouts of short sleep duration cause an acute
increase in CRP, studies have not shown if there are
long-term risks to chronic short sleep duration
• Habitual long sleep time (>9 hours) causes an increase in
CRP
Etzionin, Tamar and Giora Pillar, Sleep, sleep apnea, diabetes and the metabolic syndrome: the role of treatment. SLEEP,
Vol. 35, No. 5, 2012.
CRP, OSA and Sleep
• CRP levels are elevated in OSA
patients, particularly moderate –
severe OSA
• Increased CRP levels correlate
with more severe hypoxia,
higher day time sleepiness,
greater obesity
• Within one month of treatment
of nasal CPAP, CRP levels
decrease
http://circ.ahajournals.org/content/107/8/1129.full
Markers of Inflammation
• Interleukin 6 (IL-6) is a cytokene
– relays messages between cells
• IL-6 is released in response to
burns, trauma, infection
• IL-6 enhances the immune
system and protects against
tissue damage
• Too much or too little IL-6 can
causes systemic problems –
autoimmune disease,
malignancies
http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078635/
IL-6, OSA and Sleep
•
Habitual longer sleep duration (>9 hours) is
related to increased IL-6 levels
•
Sleep deprivation may also increase IL-6 levels –
as seen in patients with OSA
•
Elevated IL-6 is associated with OSA
•
IL-6 is increased in the upper airway tissue of
patients with severe OSA vs mild OSA
•
Noctural hypoxia is associated with increase
production of IL-6
•
After 1 month of nasal CPAP, IL-6 levels
decreased in one study, another study showed
no significant difference after 6 months of good
CPAP use
http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078635/
http://circ.ahajournals.org/content/107/8/1129.full
Markers of Inflammation
•
•
•
•
Tumour necrosis factor
(TNF-a) is a cytokene –
which are important in the
regulation of inflammation
TNF-a is one of 19 related
cytokenes
Short sleep duration is
directly related to increasing
TNF-a levels
Partial sleep deprivation for
a single night may cause
increased THF-a
Arnardottir ES; Mackiewica M; Gislason T; Teff KL; Pack Al. Molecular
signatures of obstructive sleep apnea in adults: A review and
perspective. SLEEP 2009; 32(4): 447-470.
TNF-a, OSA and Sleep
• See rapid increases in
plasma levels of TNF-a
following apneic events
• TNF-a levels decrease with
the application of CPAP
• Hours of CPAP use correlate
with decrease levels of TNF-a
Arnardottir ES et al. Molecular signatures of obstructive sleep
apnea in adults: A review and perspective. SLEEP
2009;32(4):447-470.
Steiropoulos P et al. Long-term effect of continuous positive
airway pressure therapy on inflammation markers of patients with
obstructive sleep apnea syndrome. SLEEP 2009;32(4):537-543.
A = good complaince > then 4hours per night
B = poor complaince < then 4hours per night
OSA
• Patients with OSA have
been shown to have
increased levels of TNF-a,
CRP and IL-6*
• Successful use of CPAP
has been shown to
decrease the levels of
these inflammatory
markers*
• Note – successful use is
not clearly defined
• Results are from
compliant patients
wearing CPAP for 6
months and had no
change in BMI
Steiropoulos P; Kotsianidis I; Nena E; Tsara V; Gounari E; Hatzizisi O;
Kyriazis G; Christaki P; Froudarakis M; Bouros D. Long-term effect of
continuous positive airway pressure therapy on inflammation markers of
patients with obstructive sleep apnea syndrome. SLEEP 2009;32(4):537543.
A = good complaince > then 4hours per night
B = poor complaince < then 4hours per night
Inflammatory Markers and Weight
• Large weight loss (example greater then 40 lbs)
successfully reduces some of the inflammatory
markers in obese patients – either through
traditional diet/exercise or from bariatric surgery,
(CRP and IL-6)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802719/
Hormones
• Hormones are chemical
messengers in the body.
They are sent out by a
cell or gland and travel in
the body, often in the
blood, until they find a
receptor cell.
• Hormones affect: growth,
mood, immunity,
metabolism, puberty,
reproduction, sexual
arousal, hunger/cravings,
body’s fight or flight
response.
There are more then 65 hormones in
human body
Familiar ones:
• Testosterone
• Cortisol
• Orexin
• Epinephrine
• Norepinephrine
• Melatonin
• Dopamine
• Insulin
• Serotonin
• Ghrelin
• Leptin
• Inhibin
• Oxytocin
Serotonin
• Regulates mood, emotion,
sleep, memory, learning and
muscle contraction
• Produced in brain (90%+) and
gut (2%)
• Low Serotonin can result in:
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Depression
Increased pain
Irritability
SLEEP problems (insomnia, staying
asleep)
‒ Constant fatigue
http://www.serotoninsyndrome.org/Basics/what-is.html
Serotonin and Sleep
•
Serotonin helps initiate sleep and regulate sleep
•
Low levels of serotonin may increase sleep onset and
effect deep sleep
•
Serotonin uptake inhibitors, such as paroxetine (paxil),
have been show to decrease AHI in NREM sleep*
•
Mixed-profile serotonin drugs, such as mirtazapine
(remeron), have been shown to decrease AHI – however
weight gain and sedation are known side-effects of
medication so it is not recommend for treatment of OSA**
*Effect Of Serotonin Uptake Inhibition On Breathing During Sleep And Daytime Symptoms In Obstructive Sleep
Apnea Holger Kraiczi,1 Jan Hedner,1,2 Pia Dahlöf,3 Hasse Ejnell,4 and Jan Carlson 2 Sahlgrenska University
Hospital, S
413 45 Göteborg, Sweden
**Efficacy of Mirtazapine in Obstructive Sleep Apnea SyndromeDavid W. Carley. PhD1-3;
Christopher Olopade, MD2; Ge S. Ruigt, PhD4; Miodrag Radulovacki, MD,PhD2-3 University of
Illinois at Chicago, Chicago, IL; 4Translational Research Department, NV Organon, Oss, The
Netherlands
Serotonin and OSA
• Serotonin release stimulates
upper airway muscle activity
via the hypoglossal nerve.
• Withdrawal of serotonin
causes atonia in the
hypoglossal nerve causing a
reduction in upper airway
patency
• OSA, particularly in REM, is
resistant to serotonin
therapy*
Serotonin uptake inhibition in sleep apnea—Kraiczi et al
SLEEP, Vol. 22, No. 1, 1999
*Tonic Respiratory Activity in Sleep and Wakefulness—Orem et al
SLEEP, Vol. 25, No. 5, 2002
Can serotoninergic agents treat OSA?
A review of various therapies for treatment of OSA found
in regards to serotoninergic agents:
Study 1 – 20mg of fluoxetine (prozac) for 4 weeks reduced AHI in
participants, but not to a statistically significant degree and did not
change the number of desaturations.
Study 2 – studied the effects of single dose of paroxetine (paxil) on
AHI and geneioglossus muscle activity. Found no effect of single
dose paroxetine on AHI, but it did increase muscle activity.
Study 3 – studies 6 weeks of paroxetine therapy which did result in
statistically significant changes in AHI with decreased AHI in NREM
sleep and no change in AHI in REM. Overall, did not improve
participants subjective sleepiness
A Review by Veasey SC, Guilleminault C, Strohl KP et al. Medical therapy for obstructive sleep apnea: a aeview by the
medical therapy for obstructive sleep apnea task force of the standards of practice committee of the american
academy of sleep medicne. SLEEP 2006;29(8):1036-1044.
Ghrelin (discovered in 1999)
•
Ghrelin is produced in the gi tract – mainly
stomach but also hypothalmus, kidney,
placenta and pituitary gland, receptors are in
the pituitary gland and hypothalmus
•
Ghrelin stimulates:
– Growth hormone
– Appetite – promotes hunger, food
intake
– Gastric activity – stimulates emptying
– Decreases fat use which may induce
adiposity
•
Gherlin concentrations are reduced in
obese patients
•
Ghrelin activates same areas of the brain
that drug use “rewards” it is critical in brain
processing – adapting and learning
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gh
relin.html
Ghrelin
• “ghre” = grow/growth
• Levels are high (increasing hunger sensation)
before eating and decrease after eating
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/ghrelin.html
Ghrelin and Sleep
• Has variable effects on
sleep/wake activity
• Short sleep = higher ghrelin
levels 14.9% higher in 5
hours of sleep vs. 8 hours
• Subjects reported higher
hunger after just 1 night of
total sleep deprivation
Schmid, SM et al. A single night of sleep deprivation increases
ghrelin levels and feelings of hunger in normal-weight
men. 2008
Ghrelin and sleep time
Schmid, SM et al. A single night of sleep deprivation
increases ghrelin levels and feelings of hunger in
normal-weight men. 2008
Ghrelin and Sleep Disordered Breathing
• Serum ghrelin levels are higher in patients with
OSA as compared to controls
• There is a positive correlation to ghrelin levels
and AHI
• There is a positive correlation between ghrelin
levels and Epworth Sleepiness Scale.
Ursavas, A et al. Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of
obesity. Annals of Thoracic Medicine Vol. 5(3) July-September 2010.
Does CPAP help?
• After 2 days on CPAP, ghrelin levels decreased in
most OSA patients.
• Serum ghrelin levels while on CPAP were only
slightly higher then control group levels.
Ursavas, A et al. Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role
of obesity. Annals of Thoracic Medicine Vol. 5(3) July-September 2010.
Leptin (discovered 1994)
• Leptin – appetite suppressant, helps with weight
control, saiety, fat distribution (central obesity
“apple shape”)
• Leptin resistance is present in obese patients and
patients with OSA (even those who are not obese)
• Leptin has a positive correlation with AHI
• Poor sleep and sleep deprivation causes
decreases in Leptin
http://www.stanford.edu
It’s ALL connected somehow!
Remember hyperinsulinemia?
How is it related to Leptin?
• Leptin, a hormone secreted by fat cells, is an
important part of weight regulation. Leptin acts
to control food intake and energy expenditure.
Leptin concentrations increase with obesity
and tend to decrease with weight loss. This is
important because leptin levels correlate with
insulin levels (both are high in
hyperinsulinemia)
http://www.jewishhospitalcincinnati.com/cholesterol/Research/insulin_resistance.html
Leptin and Sleep duration
• Reduced sleep duration is
associated with increased
morning leptin levels.
• Positive association of
leptin and self-reported
sleep time.
Penev, Plamen. Short sleep and circulating adipokine
concentrations: does the fat hit the fire? SLEEP.
Vol. 34, No.2, 2011.
• In a study comparing
well rested and sleep
deprived individuals,
researchers found
participants who had
too little sleep (four
hours or less)
consumed more
calories and
gravitated towards
high-fat, high protein
foods.
"Sleep Deprivation Spurs Hunger" - CNN Health, March 2011
Leptin and OSA
In some studies:
• Patients with OSA have increased leptin
levels when compared to controls of
similar weight.
• Increases in leptin levels correlate to
severity of OSA.
Other studies:
• Suggest that hypoxemia during sleep is
determinant of serum leptin levels more
so then OSAS.*
• Suggest that confounding factors such
as obesity, hypercapnia and
sympathetic nervous system activity in
OSA patients may also influence leptin
levels.*
Levy,P. Bonsignre, MR and J. Eckel. Sleep, sleep-disordered breathing and
metabolic consequences. European Respiratory Journal. Vol. 34, No 1.
2009.
*Ursavas, A et al. Ghrelin, leptin, adiponectin, and resistin levels in sleep
apnea syndrome: Role of obesity. Annals of Thoracic Medicine Vol.
5(3) July-September 2010
Leptin and CPAP
• Successful treatment
with CPAP decreased
plasma leptin levels –
positive correlation
with decreasing AHI
• Fasting leptin levels
decreased in patients
after 8 weeks of CPAP
use – even where BMI
remained constant*
Fasting leptin levels :
(○) in obstructive sleep apnoea (OSA) patients
(□) controls*
Sanner, BM, et al. Influence of treatment on leptin levels in
patients with obstructive sleep apnoea. 2004
*http://erj.ersjournals.com/content/22/2/251.full
Cortisol
• Secreted by the adrenal
glands
• Known as the “stress
hormone”
• Makes blood pressure rise
• Increases blood sugar
levels
• Is part of the “fight or
flight” response
http://www.vaxa.com/sleep-cortisol.cfm
Cortisol and Sleep
• Cortisol is part of our
wakefulness – the cyclical
release governs our level of
wake
• In the morning shortly after
waking, cortisol levels
increase, promoting wake
• In the evening, cortisol levels
decrease allowing for
relaxation and sleep.
• People with insomnia secrete
higher cortisol levels in the
evening before bedtime.
http://www.vaxa.com/sleep-cortisol.cfm
Cortisol and Sleep
• Chronic stress causes
cortisol levels to
remain elevated
• Can result in poor
sleep:
–
–
–
–
Fragmented
Shallow
Frequent arousals
Delayed sleep onset
http://www.vaxa.com/sleep-cortisol.cfm
Cortisol & OSA
• Untreated OSA is associated
with elevated cortisol levels*
• Additional to the chronic
intermittent hypoxia seen with
OSA the frequent arousals
cause sympathetic activity
leading to elevated cortisol
levels
*http://jcem.endojournals.org/content/94/11/4234.abstract
Arnardottir ES et al. Molecular signatures of obstructive sleep apnea in adults: A review and perspective. SLEEP 2009;32(4):447-470.
Autonomic Nervous System
Body at rest
Fight or Flight
Cortisol & CPAP
• After 3 months of treatment with CPAP, cortisol
levels decrease*
• Patients with severe OSA showed decreases in
evening cortisol levels after CPAP therapy**
• A review of 15 studies of the relationship between
cortisol and OSA showed conflicting results.
Partially due to cortisol samples only being from
one time period, poor controls and infrequent
sampling.
*http://jcem.endojournals.org/content/94/11/4234.abstract
**http://www.ncbi.nlm.nih.gov/pubmed/19375124
http://www.ncbi.nlm.nih.gov/pubmed/21803621
Take away
• It’s all connected!
• Sleep impacts the whole body.
• How can you help your patients connect the
dots for healthy sleep?
Thank you!
Sleep Well!
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