OVERWEIGHT AND OBESITYocw.usu.ac.id/course/download/1110000095-metabolism... · Obesity is a...
Transcript of OVERWEIGHT AND OBESITYocw.usu.ac.id/course/download/1110000095-metabolism... · Obesity is a...
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OVERWEIGHT AND OBESITY
Dharma Lindarto
Div. Endokrin-Metabolik
Departemen Penyakit Dalam FK USU/RSUP H Adam Malik Medan.
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Defining obesity
• Obesity - an excessive accumulation of body
fat sufficient to impair health
WHO 894 Obesity Report
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Obesity is a Growing Problem
• 127 million adults in the U.S. are overweight, 60 million obese,
and 9 million severely obese.
• 64.5 percent of U.S. adults are overweight (BMI≥25)
• 30.5 percent are obese (BMI≥30)• 30.5 percent are obese (BMI≥30)
• 4.7 percent are severely obese (BM≥40)
• Obesity is the No. 2 preventable cause of death and disability
(smoking is #1)
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Media coverage of obesity
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Adipose Tissue
White adipose tissue
• Stored under the skin, in mesenteries and omentum, behind the peritoneum
• Primarily fat, also small amounts of protein and water
• Stores triglycerides,
Brown adipose tissue
• Large amounts in infants, small amounts in adults
• Found primarily in scapular, sub-scapular areas
• Heat production, cold adaptation, dissipation of excess energy
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Dysfunctionaladipocyte
Adipose Tissue Mass vs. Function
Dysfunctional adipose tissue
without increase in mass
Dysfunctional adipose tissue with increase in
mass
Increased number of
enlargedadipocytes
Normaladipose tissue
Abnormal cytokine productionInflammation���� NEFA
Systemic Insulin Resistance
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Abnormal production of hormones
(Adipocytokines ) in fat
���� Lactate���� Angiotensinogen
���� Fat ���� Fat
���� Lipoprotein Lipase
���� IL - 6
Hypertension
InflammationDyslipidemia
Type 2 DM
���� Leptin
���� Adipsin (Complement D)
���� TNF- αααα
���� FFA���� Fat
Stores���� Fat
Stores
���� Plasminogen Activator Inhibitor 1
(PAI-1)
����Resistin
����AdiponectinAdiponectinDM=diabetes mellitus; FFA=free fatty acid; PAI-1=plasminogen activator inhibitor-1; TNFα=tumor necrosis factor alpha; IL-6=interleukin 6.
Slide: After Dr. G Bray
���� Insulin
����Estrogen Thrombosis
Type 2 DM
Arthritis
ASCVD
Asthma
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Adipocytokines
• The term ‘adipocytokines’: adipocyte-derived biologically active molecules which may influence the function as well as the structural integrity of other tissues
• Some examples of these substances are:
- leptin,
- acylation-stimulating protein (ASP),
- tumor necrosis factor-a (TNF-a),
- plasminogen activator inhibitor-1 (PAI-1)
- interleukin-6
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Adipocytokines
• Leptin is considered to be a fundamental signal of satiety to the brain and has a variety of actions, ranging from interference with sympathetic activity to hematopoiesis and reproductive function
• ASP increases triglyceride synthesis by increasing adipocyte • ASP increases triglyceride synthesis by increasing adipocyte glucose uptake, activating diacylglycerol acyltransferase, and inhibiting hormone-sensitive lipase
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• TNF: is involved in insulin resistance in obesity
• PAI-1: is a well-recognized causative factor for vascular
thrombosis
• Resistin; adipose-specific cysteine-rich protein with a • Resistin; adipose-specific cysteine-rich protein with a
capacity to impair insulin sensitivity and glucose
tolerance in murine models
• Adiponectin ; have anti-atherogenic and anti-inflammatory
properties
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AutonomicNervousSystem
Hypothalamus, etc
External Factors
Weight is controlled by a feedback system.
GhrelinGhrelin
PYYPYY
CCKCCK*
EfferentAfferent EC-CB1
Vagus Nerve
Food IntakeGut and Liver
Pancreas
System
Energy Expenditure
Adipose Tissue
Aronne LJ. Adapted from Campfield LA, et al. Science. 1998;280:1383-1387; and Porte D, et al. Diabetologia. 1998;41:863-881.
Adrenal Cortex
Energy Balance
and Adipose Stores
Meal Size
Adrenal Steroids
Leptin
Insulin
External Factors
food availability,
palatability
Adiponectin
CCKCCK*
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The paraventricular &arcuate nuclei contain neurons capable of stimulating/inhibiting food intake.
Y1R/Y2R denote subtypes of the neuropeptide Y (NPY) rec
MC4R melanocortin 4 rec
Korner J and R Leibel NEJM 349;10
2003
Sugars please Sugars please our brain, our brain, promote promote insulin insulin
secretionsecretion
MC4R melanocortin 4 rec
PYY peptide YY 3–36,
GHsR GH hormone secretagogue rec
AgRP agouti-related protein,
POMC propio o melanocortin
a-MSH a -melanocyte–stimulating protein
LEPR leptin rec, and INSR insulin rec.
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Estimation of Body Fat
• Bioelectrical impedance
– Low-energy current to the body that measures the resistance of electrical flow
– Fat is resistant to electrical flow; the more the resistance, the more body fat you have
• DEXA (dual x-ray photon absorptiometry)
– An X-ray body scan that allows for the determination of body fat
• Infrared light
– Assess the interaction of fat and protein in the arm muscle
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Body Mass Index (kg/m2)
Dose - Response Risk Relationship
Underweight < 18.5
Normal 18.5 - 25Normal 18.5 - 25
Overweight 25 - 30
Obese > 30
– Class I 30 - 34.9
– Class II 35 - 39.9
– Class III >40
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Kategori BMI (kg/m2) BMI Asia
Underweight < 18.5 < 18.5
Normoweight 18.5 - 24.9 18.5 - 22.9
Overweight: > 25 > 23
BMI Criteria (WHO 2000)
Overweight: > 25 > 23
Pre-obese 25.0 – 29.9 23.0 – 24.9
Obese I 30.0 - 34.9 25.0 - 29.9
Obese II 5.0 - 39.9 > 30.0
Obese III > 40.0
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Waist Circumference
Waist circumference, independent of
BMI / weight, confers additional
health risk with:health risk with:
– Glucose intolerance / Diabetes
mellitus
– Hypertension
– Dyslipidemia
Important - WC in any weight category
confers similar risk
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Central AdiposityCentral Adiposity
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Regional Distribution
• The regional distribution of body fat affects risk factors
for the heart disease and type 2 diabetes
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Body Fat Distribution: Gynecoid
• Lower-body obesity--Pear shape
• Encouraged by estrogen and progesterone
• Less health risk than upper-body obesity
• After menopause, upper-body obesity appears• After menopause, upper-body obesity appears
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Body Fat Distribution: Android
• Upper-body obesity--apple shape
• Associated with more heart disease, HTN, Type II Diabetes
• Abdominal fat is released right into the liver• Abdominal fat is released right into the liver
• Encouraged by testosterone and excessive alcohol intake
• Defined as waist measurement of > 40” for men and >35” for
women
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Obesity: Causes and ConsequencesConsequences
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Etiology:
i) Enzyme deficiency - responsible for alpha-glycerophosphate oxidation.
ii) Differences in thermogenesis - thin people are better able to dissipate excess calories through better able to dissipate excess calories through
heat production.
iii) Reduced ATPase activity - results in decreased ability to burn calories.
iv)"Hibernation response" - relic of human
evolutionary past initiates overeating.
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Etiologyv) Genetic
– inheritance of increased # and size of fat cells
– child with one obese parent has 40% chance
– two obese parents has 80% chance
vi) Socioeconomic factors
– Obesity is more common:
• children & adults from lower socioeconomic grps
• black vs white women
• white vs black men
vii) Psychological - psychogenic component in 90% of cases, however, it is NOT primary cause.
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Obesity
���� FFA
�TG
���� HDL
���� Blood
pressure ���� Insulin resistance
���� Blood glucose ���� Blood glucose
Type 2 diabetes
Cardiovascular disease
Metabolic syndrome : The role of obesity.
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Role of obesity in insulin resistance
Visceral
↑↑↑↑ Caloricintake
Sedentary
↑↑↑↑ Freefatty acids
↑↑↑↑
Oxidative
stress Insulin
Adapted from Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:1111-9.
VisceralObesity
Sedentary
lifestyle
Genetic
factors
↑↑↑↑ Glucose
↑↑↑↑ Lipids
stress
Inflammation
Insulin
resistance
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���� Hepatic
Insulin
Clearance
���� Portal
FFA
���� Plasma
Insulin
����Visceral
Fat Stores
Fat Cell Products and HypertensionFat Cell Products and Hypertension
���� Renal Na+
Reabsorption
Hypertension
Vascular
Constriction
Angiotensin I
Angiotensin IIAngiotensinogen
Bray GA. Contemp Diagn Obes. 1998.
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Medical Complications of Obesity: Almost
every organ system is affected
Coronary heart disease
Pulmonary diseaseabnormal function
obstructive sleep apnea
hypoventilation syndrome
Stroke
Diabetes
Nonalcoholic fatty liver diseasesteatosis
steatohepatitisDyslipidemia
Cataracts
Idiopathic intracranial hypertension
Phlebitisvenous stasis
Gall bladder disease
Gynecologic abnormalitiesabnormal menses
infertility
polycystic ovarian syndrome
Gout
Osteoarthritis
Cancerbreast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
steatohepatitis
cirrhosisHypertension
Skin
Severe pancreatitis
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Obesity Preventionand
ManagementManagement
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1. Non pharamcological1. Non pharamcological
Therapy of weight loss:Therapy of weight loss:
2. Pharmacological 2. Pharmacological
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Non pharmacological therapy
of Weight loss
Non pharmacological therapy
of Weight loss
Diet Diet i.e. Life style Diet
Exercise
Diet
Exercise
i.e. Life style
modifications
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Food Guide Pyramid
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Health Benefits of Weight LossHealth Benefits of Weight Loss
Decreased risk for cardiovascular disease.
Decrease glucose and insulin levels.
Decreased blood pressure.
Decreased risk for cardiovascular disease.
Decrease glucose and insulin levels.
Decreased blood pressure.Decreased blood pressure.
Decreased LDL and triglycerides
Increased HDL.
Decrease in severity of sleep apnea.
Reduced symptoms of degenerative joint disease.
Decreased blood pressure.
Decreased LDL and triglycerides
Increased HDL.
Decrease in severity of sleep apnea.
Reduced symptoms of degenerative joint disease.
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Treatment of Obesity
• Goal of treatment: 10% weight loss
• Caloric restriction: -500 kcal/day
• Moderate physical activity
– 30 minutes daily
• Behavioral modification
• Drug therapy
National Institutes of Health. Obes Res. 1998; 6 (suppl 2): 51S–209S.
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Impact of Weight Loss on Risk Factors
~5%Weight Loss
5%-10%Weight Loss
HbA1c
Blood Pressure
1
2
3
1
2
3Total Cholesterol
HDL Cholesterol
Triglycerides
1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753.
2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270-278.
3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S.
4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270.
3
3
3
3
4
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Pharmacological therapy
of obesity
Pharmacological therapy
of obesity of obesity of obesity
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A Guide to Selecting Treatment
BMI Category•Treatment < 24.9 25-26.9 27-29.9 30-35 35-39.9 >40
•Diet, exercise, With co- With co- + + +behavior therapy morbidities morbidities
•Pharmacotherapy With co- + + + morbidities
•Surgery With co- +morbidities
Source:Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.
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SystemSystem MechanismMechanism ExamplesExamples
DigestiveDigestive Inhibition of lipaseInhibition of lipase Orlistat(Xenical)Orlistat(Xenical)
CNSCNS Inhibit norepinephrine, Sibutramine(Meridia) Inhibit norepinephrine, Sibutramine(Meridia)
Approved for LongApproved for Long--Term UseTerm Use
Obesity Pharmacotherapy
CNSCNS Inhibit norepinephrine, Sibutramine(Meridia) Inhibit norepinephrine, Sibutramine(Meridia) serotonin and serotonin and
dopamine reuptakedopamine reuptake
Approved for shortApproved for short--term use term use
CNSCNS Norepinephrine release Phentermine, othersNorepinephrine release Phentermine, others
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Anorexic drugs Anorexic drugs
“Sibutramine”“Sibutramine”
↑↑↑↑↑↑↑↑ energy energy
expenditure by expenditure by
“Sibutramine”“Sibutramine”
↓↓ absorption absorption
of fat of fat
“Xenical”“Xenical”
“Chitosan”“Chitosan”
↓↓↓↓↓↓↓↓ gastric gastric
emptying by emptying by
“Acarbose”“Acarbose”
“Sibutramine”“Sibutramine”
↓↓ absorption of absorption of
CHO CHO
“Acarbose”“Acarbose”
“Gymenemic “Gymenemic
acid”acid”
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Conclusion
Overweight and obese individuals are more likely to
develop type 2 diabetes than their normal-weight
counterparts.
In addition, the incidence of insulin resistance,
hyperinsulinemia, and the insulin resistance syndrome is
greater as BMI increases.
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This is the “at
risk”patient
I’m talking about
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Chronic kidney disease
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Metabolic syndrome as
predictor of CVD
•MS increases risk of CHD
•MS predicts 25% of all new-onset CVD
•10-year risk of MS in men is between 10-20%
•Women with MS
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Approaches to the Treatment of the Metabolic Syndrome
Behavioral
Weight loss
Increased physical activity
Pharmacological (treat underlying conditions)
Lipid disordersLipid disorders
Hypertension
Diabetes
Should treatment of these underlying disorders be intensified because the subject has the metabolic syndrome?
Should underlying insulin resistance be treated in nondiabetic subjects?
No clinical trial data to date support the use of pharmacological agents to improve insulin sensitivity in nondiabetic subjects, although this is an area of active interest
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It’s everywhereSome 56 percent of South African women are now either
obese or overweight, compared to fewer than 10 percent who
are underweight. More than 17 percent of adolescents here
are overweight—for teenage girls, it's 25 percent, according
to the Medical Research Council. According to the same
report only 2% of South Africans are diabetic. Why?
World Total Cost of diabetes: $153,000,412-$286,844,446 World Total Cost of diabetes: $153,000,412-$286,844,446
depending on the degree of optimism