Obesity and diseases of civilization

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Obesity and diseases of civilization

By Amr
Abdelmonem,MD. Assistant professor of anesthesia
,surgical intensive care and clinical nutrition
in faculty of medicine, Cairo university Member
of North American Association For The Study Of
Obesity Member of the American society of
regional anesthesia and pain medicine
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The O WordObesity

• 1998, world health organization defined
  overweight and obesity based on
• Body Mass Index
• ( BMI Kg / m2)
• Over weight 25.0 to 29.9
• Class 1 obesity 30.0 to 34.9
• Class 2 obesity 35.0 to 39.9
• Class 3 obesity 40.0 or greater
• BMI is not a measure of body composition
• BMI is an important correlate of impaired
• HRQL(health related quality of life)

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National institutes of health of the US have
recently recommended weight Management based on
Standardized cut- offs for BMI at 25 and 30 Kg/m2
and

• On waist circumference ( action levels)
• Minimum circumference between lower rib margin
  and iliac crest
• Action level 1 at 94 cm in men and 80 cm in women
• Action level 2 at 102 cm in men and 88 cm in
  women
• Greater than action level 1 individuals are at
• increased health risk ,should avoid weight gain
• Greater than action level 2 are at high health
  risk ,
• should seek Professional help

NICK CIRCUMFERENCE measurement is a simple and
time-saving screening measure that can be used to
identify overweight and obese patients. Men with
NC lt37 cm and women with NC lt34 cm are not to be
considered overweight
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Adipose Tissue vs. Fat
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Traditional Adipose Tissue Classification

• Classical anatomy was mainly organ-centered,
  without recognizing the specialized organ-like
  functions of different tissues
• This was especially true of adipose tissue, which
  only recently has been recognized as an
  "endocrine organ
• N Engl J Med .20013451345
• Simple anatomic adipose tissue groupings
  subcutaneous adipose tissue, organ-surrounding
  adipose tissue, interstitial adipose and adipose
  tissue in bone marrow
• Adipose tissue is also named according to special
  biological functions, such as white, mammary
  gland, brown, and bone marrow adipose tissues

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Recent proposed Classification of total body
adipose tissue Shen et al,Obes Res.2003111
Subcutaneous
Internal
Superficial
Visceral
Non- visceral
Deep
Intramuscular Perimuscular Orbital
Intrathoracic
Intraabdominopelvic
Intrapricardial
Intraperitoneal
Extrapritoneal
Extrapricardial
Intraabdominal
Intrapelvic
Parametrial Retropubic Paravesical Retrouterine
Pararectal Retrorectal
Preperitoneal
Retrroperitoneal
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Metabolic syndrome
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What is metabolic syndrome?

• Metabolic syndrome is a collection of health
  risks that increase the chance of developing
  heart disease, stroke, and diabetes.
• The condition is also known by other names
  including Syndrome X, insulin resistance
  syndrome, and dysmetabolic syndrome.

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What are these health risks? ATP III
Guidelines
WHO Guidelines Abdominal
Obesity   Waist Circumference
Waist/Hip
Ratio  Men gt 40 inches
 gt0.90  Women gt
35 inches
 gt0.85 Other Variables   Triglycer
ides ?150 mg/dL
? 150 mg/dL HDL-Cholesterol  Men lt
40 mg/dL
lt35 mg/dL  Women lt 50 mg/dL

lt39 mg/dL Blood Pressure ?130/ ?85 mm Hg
gt140/gt90 mm
Hg Fasting Glucose ?110 mg/dL
110 mg/dL WHO guidelines
also include microalbuminuria (gt20 µg/min or
albumincreatinine ratio gt30 mg/g).
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The pathogenesis of metabolic
syndrome
Complex interplay of a still largely unknown
genetic background with environmental lifestyle-
related factors
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Genetic Background
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Environmental lifestyle-related factors
When we eat ,our bodies break down the food into
its basic components ( protein- carbohydrates-
fat), and absorbs them into blood stream ? rise
in blood sugar ? pancreas will release insulin?
moves sugar into cells? either burned for energy
or stored away as fat in fat cells or glycogen
in liver and muscles
Years of dietery abuse in susceptible patients ?
malfunctioning of insulin sensors ?
hyperinsulinemia
Continued dietery abuse ? insulin sensors to
sluggish ? insulin resistance
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The link between visceral adipose tissue and
metabolic syndrome

• Direct exposure of liver cells through the portal
  circulation to high concentrations of free fatty
  acids derived from visceral adipose tissue is
  responsible for metabolic complications of
  abdominal obesity
• Gabrielsson et al,Obes Res.200311699
• Adipocytokines (leptin ,adiponectin) factors
  released from adipose tissue responsible for
  mediating insulin resistance.
• Pischon et al,Obes Res.2003111055

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Markers of insulin resistance

• Hypertriglyceridemia
• HDL
• Hypertension
• Hyperinsulinemia
• Abdominal obesity
• Hyperglycemia
• Recently Marjo etal , proven liver fat
  accumulation as an important marker
• ( Obes Res
  2002 10 859)

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Obesity
Lets walk through the fat metabolism pathway and
follow the flow of fat molecules
Fat travels in the form of triglycerides ? at
cells ? ezymatic breakdowen ? fatty acids enter
the cells ?mitochondria ? breakdowen fat ? in
order to enter mitochondria ,fats need carnitine
? insulin inhibitsFat- carnitine shuttle system
? fats move back into blood Glucagon accelerates
this shuttle system
Muscle ,liver, kidney, lung, heart and other
cells break down fat
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Fat cells merely store the fat molecules !
Two enzyme systems on the surface of fat cells
regulated by insulin and glucagon
Insulin stimulates lipoprotein lipase that
transports fatty acid into fat cells
Glucagon stimulates sensitive lipase that
releases the fat from fat cells into the blood
Although we cannot control lipoprotein lipase
directly, we can control It indirectly by
cotrolling the metabolic hormones ,insulin and
glucagon
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DYSLIPIDEMIA

• Functions of cholesterol
• Adrenal hormones and sex hormones
• Main component of bile acids
• Essential for normal growth and development of
  brain and nervous tissue
• Gives the ability of skin to shed water
• Precursor of vitamine D in the skin
• Normal growth and repair of tissues
• Transportation of triglycerides

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Where does cholesterol come from?
80 comes from the body itself , every cell in
the body is capable of making its own
cholesterol , most dont and rely instead on
that made in the liver and skin.
Cholesterol and triglycerides are insoluble in
blood
Lipoproteins are envelops that enclose
cholesterol and triglycerides Making them
soluble in blood,so that they can be transported
to tissues
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Sequence of events in the life of lipoproteins
Liver
Makes and release VLDL
HDL
Released to tissues Deposited in coronary
arteries
TRIGLYCERIDES WITH CHOLESTEROL
Scavenges cholesterl From tissues carries Through
blood Hands it off to VLDL
Removed by liver
TRI AND CHOLES
CholesteroL rich
MATURE VLDL
Triglycerides Released to blood And tissues
LDL
Cholesterol Bulk tri
LDL
More triglycerides release
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When the level of cholesterol inside the cells
falls ? LDL receptors Attach to the surfaces of
the hepatic cells? invaginate LDL cholesterol By
endocytosis
Obese patients with insulin resistance have LDL
receptors dysfunction
Cholesterol synthesis inside the cells depends
on an enzyme named 3- hydroxy-3
methyl-glutaryl-coenzyme A reductase
Couple of hormones affect the activity of the
rate limiting enzymeHMG-CoA reductase
INSULIN AND GLUCAGON
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Diet and cholesterol quiz
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Patient with the following
findingTotal cholesterol 240 LDL 160
HDL35Total/ HDL 6.85 LDL/HDL 4.57
Diet 1 Diet 2
Total cholesterol 159 mg/dl 191 mg/dl
LDL 111 mg/dl 139 mg/dl
HDL 32 mg/dl 42 mg/dl
Total /HDL 4.97 4.55
LDL/HDL 3.47 3.31
Which is better?
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Hypertension
Data from NHANES III show that the (age
adjusted prevalence) Of high blood pressure
increases progressively with higher levels Of
BMI in men and women
High blood pressure is defined as
SBP? 140 mm Hg or MBP ? 90 mm Hg or currently
taking antihypertensives
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What is the etiology that connects obesity and
hypertension?
Hyperinsulinemia and insulin resistance
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• Mechanism
• Increased sodium retention
• Increased sympathetic nervous system activity
• Alteration in the mechanics of blood vessels

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The precise mechanism whereby weight loss
results in a decrease in Blood pressure is
unknown .

• However
• It is known that weight loss is associated with
• ? vascular resistance,total blood volume and
  cardiac output
• Improvement in hyperinsulinemia and insulin
  resistance
• ? sympathetic nervous system activity
• Suppression of the activity of renin angiotensin
  aldosterone system
• Recently ,serum angiotensin converting enzyme
  activity declines with modest weight loss.

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Type II Diabetes mellitus

• It represents 90 of all cases of diabetes.
• Requires years of underlying metabolic
  disturbance before symptoms become apparent
• The development and diagnosis usually follows
  weight gain
• In Type I and Type II diabetes blood sugar is
  elevated but for different reasons

• Type I there is no insulin to hold it down by
  moving it into cells

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• Type II the cells become resistant to insulin
  that even large amounts cant adequately move the
  sugar into cells
• In early stages there is hyperinsulinemia ,later
  pancreatic beta cells wear out from constantly
  producing insulin under stimulation of
  hyperglycemia

• Resistin is a protein secreted by fat cells as a
  signal from adipose tissue linking obesity to
  insulin resistance and type II diabetes
• Liese et al,
  Eur J Nutr.200140282
• Increased White blood cell count is correlated
  with insulin resistance in diabetic obese females
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  Pannacciulli et al,Obes Res.2003111232

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Coronary artery disease

• Observational studies have shown that
  overweight,obesity, and VAT are directly related
  to cardiovascular risk factors
• ( ? cholesterol , ? LDL, ? triglycerides,
  hypertension, ? fibrinogen,hyperinsulinemia , ?
  HDL, ?plasminogen activator inhibitor )

The term "Syndrome X" refers to a heart condition
where chest pain and electrocardiographic changes
that suggest ischemic heart disease are present,
but where there are no angiographic findings of
coronary disease.
RECENTLY Complement 3 and acute phase proteins is
the immunological link between central obesity
and CHD
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• Recent studies have shown that risks of nonfatal
  myocardial infarction and CHD death increase with
  increasing levels of BMI
• In British, Swedish, Japanese and US populations
  , CHD incidence increased at BMIs above 22 and an
  increase of 1 BMI unit was associated with
• 10 increase in the rate of coronary events
• Recent study has found that obese CHD patients
  are younger and and are hospitalized more
  frequently during the first 10 years of their
  illness than the non-obese

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Obesity and cardiac dysrhythmias(prolonged Q-T
interval)

• Q-T interval is usually measured in lead II , and
  is corrected for heart rate .
• Q-Tc measured Q-T ? square root of R-R interval
• Prolonged Q-T interval reflects prolonged
  repolarization of the ventricle
• Proposed mechanism is increased SNS activity
• Recent study had found that Prolonged Q-T
  interval is associated with abnormal WHR ,higher
  levels of FFA and hyperinsulinemia in obese women
  .
• Wight loss leads to normalization of Q-Tc with
  attenuation of hyperinsulinemia
• Esposito et al,Obes Res.200311653-659

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Oxidant Stress
Imbalance
Between
Formation Of Reactive
oxygen/nitrogen species
(ROS/RNS) And
Antioxidants
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Pathologic stress ?
Induces monocytes to release mediators
(TNF? and interleukins 1-6-8) ?
Activates PMNs ?
Release ROS(superoxide (O2-), hydrogen peroxide,
hypochlorite, nitric oxide (NO), hydroxyl radical
?
Induce tissue injury by

• damaging DNA
• Cross linking cellular proteins
• Peroxidation of membrane lipids ?
• Diminishing membrane fluidity
• Increasing membrane permeability

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Oxidant Stress and Obesity

• Adipocytes and preadipocytes have been identified
  as sources of inflammatory cytokines
• including TNF- , interleukin (IL)1-ß, and IL-6.
• Stimuli capable of inducing cytokine release from
  adipocytes may include
• lipopolysaccharides, intracellular
  triglycerides, and catecholamines

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We could predict that
The accumulation of intracellular triglycerides
or tissue adiposity promotes increased oxidant
stress Therefore reduction of total body fat
through diet and/or exercise may be an effective
means of reducing systemic inflammation and
oxidant stress.
Consistent with this prediction
Reductions in plasma markers of oxidant stress
and in ROS generation by isolated leukocytes have
been observed after 4 weeks of energy
restriction and weight loss. Dandona et al. J
Clin Endocrinol Metab,2001 86355-363
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Good news
Physical activity ? Decreases adipose derived
inflammatory mediators Activates signaling
pathways that lead to increased synthesis of
intracellular antioxidants and antioxidant
enzymes and decreased ROS production
Miyazaki et al, Eur Appl Physiol.2001 841-6
Pischon et al, Obes Res.2003111055
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Obesity And Diseases
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Obesity and cancer

• Strong risk factor for esophageal cancer
• Uterine and gall bladder cancer in obese women
• High risk for colon and prostate cancer in obese
  males
• Breast cancer for obese postmenopausal women

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Obesity and muscles and bones

• Obesity places stress on bones and muscles
• High risk for hernias ,low back pain and
  aggravation of arthritic conditions
• High risk for carpal tunnel syndrome

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Obesity and gallstones

• The incidence of gallstones is significantly
  higher in obese women and men
• The risk of stone formation is also high if a
  person loses weight too quickly

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Obesity and lungs

• Strong risk factor for adult onset asthma.
• Increased risk of hypoxemia and detrimental work
  of breathing
• Pickwickian syndrome

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Obesity and sleep apnea and sleep disorders

• Obese tend to fall asleep faster and sleep longer
  during the day
• At night ,it takes them longer to fall asleep
  they sleep less than others.
• When the upper airways relaxes and collapses at
  intervals during sleep ,thereby temporary
  blocking the passage of air (sleep apnea)
• Symptoms morning headach,fatigue and
  irritability
• Side effects dysrhythmias,stroke ,right sided
  heart failure and car accidents
• Sleep apnea deprives patients from REM sleep
• REM sleep the dreaming phase of sleep,necessry
  for emotional wellbeing
• Obesity leads to sleep apnea which leads to loss
  of REM sleep which leads to raising of BMI

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OBESITY AND EATING DISORDERS

• Binge eating about 30 of obese are binge
  eaters ,who typically consume 5000 to 15000
  calories in one sitting
• To be diagnosed as a binge eater ,person has to
  binge twice a week for 6 months
• Bulimia binge eating followed by purging in
  order to lose weight
• Anorexia severe weight loss and is life
  threatening

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Why treat overweight and obesity?

• Not only
• to improve the BODY IMAGE
• But also
• to reduce the
• OBESITY RELATED COMORBIDITIES

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THANK YOU