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Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
(To be submitted in duplicate)
1.
Name of the candidate and
address
Dr. RIYAZ MOIDEEN,
S/O PATHOOR MOIDEEN,
MALAPPURAM DISTRICT,
KERALA 676309
2.
Name of the Institution
M.S.RAMAIAH MEDICAL COLLEGE,
BANGALORE
3.
Course of the study and
subject
M.D. RESPIRATORY MEDICINE
4.
Date of Admission to
Course
1st June, 2011
5.
Title of topic
PREVALENCE OF OBSTRUCTIVE
SLEEP APNEA (OSA) IN PATIENTS
WITH METABOLIC SYNDROME.
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6.BRIEF RESUME OF THE INTENDED WORK:
6.1 BACKGROUND:
Short sleep duration and poor quality of sleep, increasingly common in our modern
society, have many effects on our endocrine and metabolic function. Sleep is a major buffer
for hormonal release, glucose regulation and cardiovascular function1. Sleep-disordered
breathing (SDB) disrupts sleep pattern and quality. Obstructive sleep apnoea (OSA) is the
most common sleep disorder being diagnosed1. It is a chronic condition that is characterized
by repetitive upper airway obstructions resulting in intermittent hypoxia and sleep
fragmentation caused by arousals 2. Obstructive sleep apnea syndrome has been associated
with an increased incidence of hypertension, stroke, and cardiovascular disease 3.
Metabolic syndrome (MS) was first described as a cluster of metabolic abnormalities,
with insulin resistance as the central pathophysiological feature, and it was labelled as
“Syndrome X
1
. It is characterized by hypertension, abdominal obesity, increased
triglycerides and blood glucose and decreased HDL cholesterol and is associated with an
increased risk for the development of type 2 diabetes mellitus and cardiovascular disease 4.
Recently, there has been great interest in the interaction between OSA and metabolic
dysfunction. In particular, OSA has been independently associated with insulin resistance,
suggesting that OSA may be an important factor for the development of type 2 diabetes and
the so called metabolic syndrome (MS) 2. Syndrome Z (SZ) is defined as the co-occurrence of
OSA and metabolic syndrome.
Though there is circumstantial evidence to implicate OSA in the development of MS, the
causal relationship remains unproven. Recent community based study on prevalence of OSA
,MS and syndrome Z in urban population of New Delhi, shows that there is a high
prevalence of OSA among the patients with MS 4 .
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6.2 NEED FOR THE STUDY
OSA in patients with metabolic syndrome is an important issue for research as the
prevalence of obesity is increasing worldwide and with this prevalence of OSA and MS will
also increase tremendously. This would require urgent public health intervention strategies,
otherwise health resources of the developing and developed nations will be overburdened 4.
OSA or snoring is shown to be independently associated with an increased prevalence of
metabolic syndrome, and this is consistent across different ethnic origins. There is a need for
further studies to reconfirm results on Indian population and polysomnography must be done
in all patients of metabolic syndrome for detection of OSA 4.
Early CPAP treatment has produced some beneficial effects on individual metabolic
components of MS hence identification and treatment of OSA in patients with MS is
essential1. There is clear evidence that sleep apnoea treatment both improves the symptoms
of sleep apnoea, particularly excessive daytime sleepiness, and lowers blood pressure. There
is some evidence that treatment also reduces cardiovascular disease risk and may sometimes
improve diabetes control5.
6.3 REVIEW OF LITERATURE:
Sleep apnoea
Sleep apnoea is part of the spectrum of disorders characterised by abnormal breathing
during sleep, which range from intermittent snoring to persistent snoring, upper airway
resistance syndrome, OSA syndrome and obesity hypoventilation syndrome5. OSA may be
associated with such symptoms as excessive daytime
sleepiness, loud snoring reported by the patient and/or his or her partner, a feeling of choking
or suffocation at night, unrefreshing or restless sleep, changes in mood and personality and
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cognitive changes. These symptoms can be readily detected using simple screening
questionnaires such as the Epworth Sleepiness Scale and Berlin questionnaires5.
Diagnosis
The diagnosis of sleep apnoea can be made using complete nocturnal polysomnography
(PSG), which records multiple channels of physiological data (EEG, EMG, EOG, pulse
oximetry, air flow, respiratory effort and ECG) . However, sleep specialists are now adopting
simpler screening studies that can even be conducted at home; these tests simply measure
oxygen saturation, nasal air flow and/or respiratory effort. The purpose of these tests is to
evaluate how many episodes of apneas and hypopneas occur through the night 5.
The severity of sleep apnoea is defined using the apnoea–hypopnoea index (AHI) or the
respiratory disturbance index (RDI), which represent the number of apnoeas and hypopneas
per hour of sleep5. Severity of sleep apnoea can be graded as mild sleep apnoea when AHI: 5
to 15 events per hour, moderate sleep apnea when AHI:15 to 30 events per hour, severe sleep
apnoea, AHI greater than 30 events per hour6.
OSA and MS
The past two decades have seen a growing recognition of the presence of various types of
metabolic dysfunction in subjects with OSA, and the association of OSA and MS was
highlighted as "syndrome Z" in the late 1990s . However, there is paucity of literature linking
MS with sleep-disordered breathing. There is growing experimental and clinical evidence for
an independent contribution of OSA towards the development and/or severity of individual
metabolic components of MS. On the contrary, MS and its components—in particular, obesity
and insulin resistance/diabetes mellitus—may have a conducive influence on the development
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of sleep apnea, and it has been proposed that OSA itself may well be a "metabolic disorder"
and a component of MS 2. (Figure I)
FIG:1 Possible mechanistic links between obstructive sleep apnea, metabolic syndrome
and type 2 diabetes 2.
OSA may affect metabolism indirectly, by decreasing the amount and/or quality of
sleep. Sleep loss profoundly affects metabolic pathways. In healthy subjects, experimental
sleep restriction caused insulin resistance, together with increased evening cortisol and
sympathetic activation. Sleep restriction was also shown to be associated with reduced leptin
and increased ghrelin plasma concentrations and increased appetite. Modest acute sleep loss,
such as selective slow-wave sleep deprivation, may alter glucose tolerance in normal
subjects7.
A prospective study done in young adults found a significant risk of obesity in
subjects reporting short sleep duration, leading to speculation that decreased sleeping time
over the recent decades may have contributed to the increasing prevalence of obesity in the
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general population. In addition, in general population cohorts, difficulties falling asleep,
difficulties in sleep maintenance and reduction in sleep duration have been found to be
associated with an increased incidence of diabetes 7. Obesity affects upper airway anatomy
because of increased fat deposition in the neck region which in turn predisposes to upper
airway collapsibility during sleep 1.
Prevalence
The overall population prevalence of sleep apnoea in adults is between 2 and 4%, with
the condition being about twice as common in men 5. The prevalence of OSA among obese
patients has been reported to exceed 30 per cent, and 60-90 per cent of adults with OSA are
overweight, and the relative risk of sleep apnoea from obesity with a BMI >30 kg/m2 may be
as great as 101.
Treatment
Treatment options for Patients with sleep apnoea are reduction in weight, modest weight
loss, can improve symptoms of sleep apnoea. Patients who have specific abnormalities of the
palate or jaw may benefit from specific surgery, but the majority of patients will require
treatment with nasal continuous positive airway pressure (CPAP) ventilation, which has been
shown to improve symptoms of sleep apnoea in a range of studies5.
6.4 AIM OF THE STUDY
The aim is to determine the prevalence of Obstructive sleep apnoea in patients
diagnosed with metabolic syndrome.
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6.5 OBJECTIVES OF THE STUDY
To evaluate patients with metabolic syndrome for OSA.
7. MATERIALS AND METHODS:
Eighty five patients with metabolic syndrome attending M S Ramaiah Hospitals between
2011 and 2014 will be included for the study. The following data will be compiled in all
patients.
•
Clinical history and demographic data.
•
BMI (wt in kg/ht in m2)
•
Blood pressure (recorded after at least 5 minutes of rest in both arms sitting/supine
position)
•
Waist circumference (measured in a horizontal plane midway between the inferior
margin of the ribs and superior border of the iliac crest)
•
Blood samples of 5ml will be
drawn after 12 hours overnight fasting for the
measurement of lipid profile, fasting plasma glucose
•
Patients fulfilling the IDF criteria for metabolic syndrome will be screened for
symptoms of OSA (snoring, witnessed apneas and excessive day time sleepiness).
Epworth sleepiness scale will be used to screen for EDS. Physical examination will be
performed to look for upper airway anatomy. Patients with suggestive symptoms of
OSA and ESS of score more than 10 will undergo a limited polysomnography with
three channels which includes nasal airflow measurement, chest movement and pulse
oximetry.
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7.1 DIAGNOSIS OF METABOLIC SYNDROME:
According to new IDF criteria for a person to be defined as having the metabolic
syndrome they must have 1:
Central obesity – defined as waist circumference  90cm for men and  80 cm for women
(Indian population).
Plus any two of the following four factors
1) Raised TG level  150mg/dl or specific treatment for this lipid abnormality
2) Reduced HDL cholesterol <40mg/dl or specific treatment for this lipid abnormality
3) Raised B.P systolic  130 diastolic  85 or treatment for previously diagnosed
hypertension.
4) Raised FBG  100mg/dl or previously diagnosed type 2 diabetes.
7.2 DIAGNOSIS OF OSA
OSA is defined as apnoea-hypopnoea index (AHI) > 5 that is more than five episodes
per hour of cessation of breathing for at least 10 seconds 3. Apneas were defined by an 80%
or greater reduction in the airflow signal with persistent respiratory effort lasting 10 seconds
or longer. Hypopneas were defined as a 30% or greater reduction in the airflow signal with
persistent respiratory effort lasting at least 10 seconds associated with a desaturation of 4% or
greater 3.
Severity of sleep apnoea can be graded as mild sleep apnoea when AHI: 5 to 15 events
per hour, moderate sleep apnea when AHI:15 to 30 events per hour, severe sleep apnea, AHI
greater than 30 events per hour6.
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7.3 SOURCE OF DATA:
Adult patients (Out Patients and In Patients) with signs of metabolic syndrome
attending MS Ramaiah Hospitals.
7.3 STUDY DESIGN:
A hospital based cross-sectional study.
7.4 INCLUSION CRITERIA:
Patients fulfilling IDF criteria for metabolic syndrome.
7.5 EXCLUSION CRITERIA:
- Hypothyroidism
- Critically ill patients
- Patients with end stage organ disease and malignancy
- Pregnant women
7.6 SAMPLE SIZE CALCULATION:
Sample size was estimated to be approximately a minimum of 85. It was estimated
using N-master software considering a population based Indian study showed that frequency
of OSA among MS patients is primarily 66% with a relative precision (allowable error) of
10% and confidence interval of 95%.
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7.7 STATISTICAL ANALYSIS:
All the data like age, vital signs and investigations will be presented as mean and
standard deviation with 95% confidence intervals. Further differences in the proportions
between different groups with various conditions of metabolic syndrome among features with
standardizing further for their significance through Chi-square table of significance.
An attempt will be made to employ logistic regression to identify the further association
of the various components of metabolic syndrome with OSA.
7.8 Does this study require any investigations or interventions to be
conducted on patients or other humans or animals? If so, describe briefly.
Limited polysomnograpy
7.8 Has ethical clearance been obtained from your institution?
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8. REFERENCES
1. Jamie C.M. Lam & Mary S.M. Ip. Sleep & the metabolic syndrome.
Indian J Med Res 2010; 131(2): 206-16.
2. Esra Tasali and Mary S. M. Ip. Obstructive Sleep Apnea and Metabolic
Syndrome Alterations in Glucose Metabolism and Inflammation. Proc Am
Thorac Soc 2008; 5: 207–17.
3. Parish JM; Adam T; Facchiano L. Relationship of Metabolic Syndrome and
Obstructive Sleep Apnea. J Clin Sleep Med 2007;3(5):467-72.
4. Surendra K. Sharma & Vishnubhatla Sreenivas. Are metabolic syndrome,
obstructive sleep apnoea & syndrome Z sequential? - A hypothesis.
Indian J Med Res 2010; 131: 455-58
5. John Wilding and John O’Reilly. Sleep Apnoea, Obesity, Diabetes and the
Metabolic Syndrome. Eur Endocrine Dis 2007;1: 72-5.
6. Alfred P. Fishman, MD, Jack A. Elias, MD, Jay A. Fishman, MD,Text book
of Fishman’s Pulmonary Diseases and Disorders. Fourth Edition, New
York: McGraw-Hill; 2008. p.1679-735.
7. P. Lévy Et.al. Sleep, sleep-disordered breathing and metabolic
consequences , Eur Respir J 2009 ; 34 : 243-260
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9. Signature of the candidate :
10. Remarks of the guide :
This study is significant as
incidence
of metabolic syndrome and sleep
disordered breathing are noticed
increasingly now a days with advent
of newer diagnostic tools.
10.1 Name and designation of the guide : DR. K.N.MOHAN
RAO.MD,DTCD.
Professor and HOD
Department of Chest medicine ,
M.S.R.M.C,
Bangalore.
10.2 Signature of the guide :
11. Remarks of the Co-guide:
This study will be a valuable
addition to the evidence available
that links MS to OSA
11.1 Name and designation of the Co-guide :
DR. UMA MAHESHWARI.MD, DM.
Associate Professor,
Department of Chest medicine,
M.S.R.M.C,
Bangalore.
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11.2 Signature of the Co-guide :
12. Name and designation of the H.O.D : DR. K.N.MOHAN RAO,
Professor and HOD
Department of Chest medicine,
M.S.R.M.C,
Bangalore.
12.1 Signature of the H.O.D :
13. Remarks of the Principal :
13.1 Signature of the Principal:
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