Obesity Metabolic Syndrome

1. Obesity
metabolic syndrome,
atherosclerosis

2. Sponsored
Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice

3. 3
Definition
• A BMI of 25.0 to 29.9
kg per m2 is defined
as overweight;
• a BMI of 30.0 kg per
m2 or more is
defined as obesity.

4. 4
Historical Perspective
Paleolithic Era > 25,000 years ago

5. 5
Obesity - How Big A
Problem…
• 1.7 billion worldwide are
overweight or obese
• The US has the highest
percentage of obese
people.
• By 2012, only four states
had a prevalence of
obesity less than 35%.
And the numbers are
growing…

7. 7
Epidemiology of Obesity
• 31.3% of U.S. males 34.7% of U.S. females
• 30% increase in the last 10 years obesity
• (BMI 40) has also increased and affects 4.7% of
the population.
• It is predicted that in 2045 the number of obese
OSB is 1 2 populations
• Health care costs - >$100 billion/year
• Results in 300,000 preventable deaths each year
in the U.S.

9. Body Mass Index (BMI)
• the most
• widely used method to gauge obesity is
the Body Massindex (BMI) (in kg/m2),
• which is equal to
weight
height 2

10. A circumference of
waist is the
mediated index of
amount of visceral
fat, or abdominal
obesity.
Чоловіки >102 см. > 94
сm
Жінки >88 см> 80cm

11. 11
Obesity and Life Expectancy
If current rates of obesity
are left unchecked, the
current generation of
American children will be
the first in two centuries to
have a shorter life
expectancy than their
parents.
Olshansky SJ, et al. A Potential Decline in Life Expectancy
in the United States in the 21st
Century. NEJM, 352(11):1138-
1145, 2005

12. 12
Classification of Overweight
and Obesity
BMIBMI ClassificationClassification
<18.5 Underweight
– 18.5-24.9 Normal weight
– 25-29.9 Overweight
– 30-34.9 Obesity Class I
– 35-39.9 Obesity Class II
– 40-49.9 Obesity Class III
– 50 and above Super Obesity

13. 13

14. 14
What causes Obesity?
• Nutrient and Energy model of
obesity:
Metabolism
Appetite regulation
Energy expenditure
Genetics
Behavioral and cultural factors

15. 15
Contributors to weight gain
• Socio-economic status
• Smoking cessation
• Hormonal
• Inactivity
• Psychosocial/emotions
• Medications

17. 17
Medical Complications of
Obesity
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver disease
steatosis
steatohepatitis
cirrhosis
Gall bladder disease
Gynecologic abnormalities
abnormal menses
infertility
PCOS
Osteoarthritis
Gout
Phlebitis
venous stasis
Cancer
breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
Severe pancreatitis
CHD
Diabetes
Dyslipidemia
Hypertension
Cataracts
Stroke

18. 18
Nutrient and Energy
Model of Obesity
Obesity results from increased intake of energy or
decreased expenditure of energy, as required
by the first law of thermodynamics.
EnergyEnergy
IntakeIntake
AdiposeAdipose
tissuetissue
EnergyEnergy
ExpenditureExpenditure

19. Central controllers
of appetite

20. Central controllers
of appetite
Increase
factors
NPY
MCH
AgRP
Orexin
Endocan
nabinoid
Decrease
factors
α-MSH
CART
GLP-1
Serotonin
Psychological
factors
Neural
afferents
(vagal)
Gut peptides
CCK, PYY
Ghrelin
Metabolites
Glucose
Ketones
Hormones
Leptin
Insulin
Cortisol
Cultural
factors
NPY, neuropeptide Y; MCH, melanin-concentrating hormone;
AgRP, Agouti-related peptide; MSH, melanocyte-stimulating
hormone; CART, cocaine- and amphetamine-related transcript;
GLP-1, glucagon-related peptide-1; CCK, cholecystokinin.

21. Signals that impinge on the hypothalamic center
include neural afferents, hormones, and metabolites.
Vagal inputs are particularly important, bringing
information from viscera, such as gut distention.
Hormonal signals include leptin, insulin, cortisol,
and gut peptides.
Among the latter are ghrelin, which is made in the
stomach and stimulates feeding, and peptidemass
increases by enlargement of adipose cells through
lipid deposition, as well as by an increase in the
number
Appetite is influenced by many
factors that are integrated by the
brain, most importantly within the
hypothalamus

22. The growth of adipose tissue
• The process by which adipose cells are
derived from a mesenchymal
preadipocyte involves an orchestrated
series of differentiation steps mediated by
a cascade of specific transcription
factors.
One of the key transcription factors is
peroxisome proliferator-activated receptor
(PPAR-),

24. • The fact that intraabdominal adipocytes
are more lipolytically active than those
from other depots.
• Release of free fatty acids into the portal
circulation has adverse metabolic
actions, especially on the liver.
• The adipokines and cytokines secreted
by visceral adipocytes play an additional
role in systemic complications of obesity
The growth of adipose tissue

25. 1970 1980 1990 2000 2013

26. The adipocyte is an endocrine cell that
releases numerous regulated molecules
• These include the energy balance-regulating hormone
leptin, cytokines such as tumor necrosis factor (TNF)and interleukin
(IL)-6, complement factors such as factor D (also known as
adipsin), prothrombotic agents such as plasminogen activator
inhibitor I, and a component of the blood pressure regulating
system, angiotensinogen.
• Adiponectin, an abundant adipose-derived protein whose levels are
reduced in obesity, enhances insulin sensitivity and lipid oxidation
and it has vascular protective effects,
• whereas resistin and RBP4, whose levels are increased in obesity,
may induce insulin resistance.
These factors, and others not yet identified, play a role in the
physiology oflipid homeostasis, insulin sensitivity, blood pressure
control, coagulation, and vascular health, and are likely to
contributeto obesity-related pathologies.

27. Function adypotcyts
Adipocyte
Others
PAI-1
Angiotensinogen
RBP4
Complement factors
Factor D/adipsin
Enzymes
Aromatase
11-HSD-1
Substrates
Free fatty acids
Glycerol
Cytokines
TFN-
IL-6
Hormones
Leptin
Adiponectin
Adipocyte Resistin

28. 28
Leptin
• A major regulator of adaptive responses is the
adipocytederived hormone leptin, which acts through brain
circuits (predominantly in the hypothalamus) to influence
appetite, energy expenditure, and neuroendocrine function
The peptide leptin, a name derived from the Greek root leptos, meaning
thin.
• Protein hormone produced by fat cells.
• Experiment: Leptin deficient mice:
Hyperphasic
Insulin resistant
Infertile
• Leptin administration reversed all the symptoms.

29. Energy expenditure
includes the following components:
(1) resting or basal metabolic rate;
(2) the energy cost of metabolizing and storing food;
(3) the thermic effect of exercise;
(4)adaptive thermogenesis, which varies in
response to chronic caloric intake
Basal metabolic rate accounts for ~70% of daily
energy expenditure,
whereas active physical activity contributes 5–10%.
Thus, a significant component of daily energy
consumption is fixed.

30. Adaptive thermogenesis
occurs in brown adipose tissue (BAT), which plays
an important role in energy metabolism in many
mammals.
In contrast to white adipose tissue(WAT), which is
used to store energy in the form of lipids, BAT
expends stored energy as heat. A mitochondrial
uncoupling protein (UCP-1) in BAT dissipates the
hydrogen ion gradient in the oxidative respiration
chain and releases energy as heat. The metabolic
activity of BAT is increased by a central action of
leptin, acting through the sympathetic nervous
system, which heavily innervates this tissue.

31. Metabolic Syndrome X?
Syndrome ("New World")
Insulin dependent diabetes mellitus (or breach of
tolerance to carbohydrates) and insuli
resistance
 Obesity (in android type)
Dyslipidemia
Coronary Artery Disease
hypertension
Microalbuminuria
Hiperurikemiya
Hiperleptynemiya and resistance to
leptin
Violation of blood rheology

32. Insulin Resistance and Type 2
Diabetes Mellitus
• Hyperinsulinemia and insulin resistance
are pervasive features of obesity,
• Insulin resistance is more strongly linked
to intraabdominal fat than to fat in other
depots.

33. 33

34. Determination of insulin resistance (IR)?
(Formula HOMA)
rate - 59 – 161
insulin resistance - below 59%
Defining the function of beta cell
20 x insulin x 100 %
(glucose - 3.5)
rate - 70 -150
below 70% - a decline of beta-cell function
IP =
(insulin) x (glucose)
Х 100%
22,5

35. How to determine the type of distribution
of adipose tissue?
IVH =
CV
(sм)
СH
capacity waist, - measured by the smallest circumference below
the rib cage on the navel
capacity hips - for the largest circumference at the buttocks
Diagnostic value of the IVT
0,8 – 0,9
An intermediate type of distribution of
adipose tissue
< 0,8
Hinoid (peripheral) type distribution of
adipose tissue
> 0,9 m
> 0,85 F
Android (abdominal, visceral, central)
type distribution of adipose tissue

36. Treatment of metabolic
syndrome X
Weight loss
Increased physical activity
Treatment of hypertension
Antyhiperhlikemichna therapy
aspirin
lipid-lowering therapy

37. The criteria for compensation of carbohydrate metabolism in
patients with type 2 diabetes (WHO, 1998)
Indicators norm
risk
makroanhio
patiy
risk
microangio
pathies
Glycated
hemoglobin
HbAlc (%)
< 6,5 >6,5 >7,5
Capillary blood
glucose
(mmol)
After fasting
food within 2
hours (peak)
< 5,5
< 7,5
> 5,5
> 7,5
> 6,1
> 9,0

38. How activation of PPAR γ enhances the action
of insulin and normalizes blood glucose
levels?increased
differentiation
preadipotcytes
adipocytesadipocytes
PPAR γ
AvandiyaAvandiya
and insulinand insulin
liver
Decrease
formation of
glucose
in the liver
EuhlykemiyaEuhlykemiya
Reduced
lipolysis and
circulating free
fatty acids
↑insulin
sensitivity and
the capacity for
glucose
disposal /
deposition of
lipids Skeletal muscleSkeletal muscle
PPAR γγ

39. Hyperglyce
mia
Blood glucose
after meals
↓Acarbose
↓ Metformin
Capture glucose
 Metformin
 Rozihlitazon
Synthesis of
glucose
 Metformin
 Rozihlitazon
insulin secretion
 Rozihlitazon
 sulfonyl urea
 repaglinide

40. Cancer
• Obesity in males is associated with higher
mortalityfrom cancer, including cancer of the
esophagus, colon,rectum, pancreas, liver, and
prostate; obesity in females isassociated with
higher mortality from cancer of the allbladder,bile
ducts, breasts, endometrium, cervix, andovaries.
• Some of the latter may be due to increased
ratesof conversion of androstenedione to estrone
in adiposetissue of obese individuals.
• It was recently estimated that obesity accounts
for 14% of cancer

41. Bone, Joint, and Cutaneous
Disease
Obesity is associated with an increased risk of
osteoarthritis, no doubt partly due to the trauma of
added weight bearing and joint malalignment.
The prevalence of gout may also be increased.
Among the skin problems associated with obesity
is acanthosis nigricans, manifested by darkening and
thickening of the skin folds on the neck, elbows,
and dorsal interphalangeal spaces. Acanthosis
reflects the severity ofunderlying insulin resistance
and diminishes with weight loss.
Friability of skin may be increased, especially in skin
folds, enhancing the risk of fungal and yeast
infections
Finally, venous stasis is increased in the obese.

42. Pulmonary Disease
• Obesity may be associated with a number of
pulmonary abnormalities.
• These include reduced chest wall compliance,
increased work of breathing, increased minute
ventilation due to increased metabolic rate, and
decreased functional residual capacity and
expiratory reserve volume.
Severe obesity may be associated with obstructive
sleep apnea and the “obesity hypoventilation
syndrome” with attenuated hypoxic and
hypercapnic ventilatory responses.
Sleep apnea can be obstructive (most common),
central, or mixed and is associated with
hypertension.

43. Reproductive Disorders
Disorders that affect the reproductive axis are associated
with obesity in both men and women.
Male hypogonadism is associated with increased adipose tissue, often
distributed in a pattern more typical of females. In men >160% ideal body
weight, plasma testosterone and sex hormone-binding globulin (SHBG)
are often reduced, and estrogen levels (derived from conversion of
adrenal androgens in adipose tissue) are increased. Gynecomastia may
be seen.
Obesity has long been associated with menstrual
abnormalities
in women, particularly in women with upper body obesity. Common
findings are increased androgenproduction, decreased SHBG, and
increased peripheral conversion of androgen to estrogen.
Most obese women with oligomenorrhea have the polycystic ovarian
syndrome (PCOS), with its associated anovulation and ovarian
hyperandro genism; 40% of women with PCOS are obese.

44. Cardiovascular Disease
• Obesity, especially abdominal obesity, is
associated with an atherogenic lipid profile; with
increased low-density lipoprotein
(LDL)cholesterol, very low density lipoprotein,
and triglyceride;and with decreased high-density
lipoprotein cholesterol and decreased levels of
the vascular protectiveadipokine adiponectin.
• Obesity is also associated with hypertension.
Measurement of blood pressure in theobese
requires use of a larger cuff size to avoid
artifactual increases.
• Obesity-induced hypertension is associated with
increased peripheral resistance and cardiac
output, increased sympathetic nervous system
tone, increased salt sensitivity, and insulin-
mediated salt retention; it is often responsive to
modest weight loss.

45. AteroselerozAteroseleroz
A chronic, focal lesions of the
arteries characterized by
accumulation in the inner wall of
arteries apoproteyin-B-containing
lipoproteins and cholesterol,
reactive growth of connective
tissue with the formation of fibrous
plaques and their rupture,
thrombosis, calcification.

47. Адаптовано з E.Topol. Atlas of Atherothrombosis.- 2005
Consequences of obliterating
atherosclerosis of the lower extremities.

48. What Is Cholesterol?
• We may associate cholesterol
with fatty foods, but most of the
waxy substance is made by
our own bodies.
• The liver produces 75% of the
cholesterol that circulates in
our blood.
• The other 25% comes from
food.
• At normal levels, cholesterol
actually plays an important
role in helping cells do their
jobs. But cholesterol levels are
precariously high in more than
100 million Americans.

49. Symptoms of High Cholesterol
• High cholesterol does not
cause any symptoms. But it
does cause damage deep
within the body.
• Over time, too much
cholesterol may lead to a
buildup of plaque inside the
arteries. Known as
atherosclerosis, this
condition narrows the space
available for blood flow and
can trigger heart disease.
• The good news is high
cholesterol is simple to
detect, and there are many
ways to bring it down.

50. Cholesterol
Most of the cholesterol in the
blood is carried by proteins
called low density ipoproteins
or LDL.
This is known as the bad
cholesterol because it
combines with other
substances to clog the
arteries.

51. 'Good' Cholesterol
Up to a third of blood
cholesterol is carried by
high-density lipoproteins
or HDL.
This is called good
cholesterol because it
helps remove bad
cholesterol, preventing it
from building up inside the
arteries.
The higher the level of HDL
cholesterol, the better.
People with too little are
more likely to develop
heart disease.
Eating healthy fats, such as
olive oil, may help boost
HDL cholesterol.

52. Triglycerides
The body converts excess
calories, sugar, and alcohol into
triglycerides, a type of fat that is
carried in the blood and stored in
fat cells throughout the body.
People who are overweight,
inactive, smokers, or heavy
drinkers tend to have high
triglycerides, as do those who
eat a very high-carb diet.
A triglycerides score of 150 or
higher puts you at risk for
metabolic syndrome, which is
linked to heart disease and
diabetes.

53. Normally:
cholesterol plasma 5.2 mmol / l,
triacylglycerol - 2.3 mmol / l,
beta-lipoprotein - 6000 mg / l.
Land Surveying basic level of blood
lipids:
total cholesterol - 5,2-6,2 mmol / l,
triacylglycerol - 2,3-4,5 mmol / l.
Elevated levels of major blood lipids:
total cholesterol -> 6.3 mmol / l,
triacylglycerol -> 4.5 mmol / l.
Атеросклероз

54. 500432210
The relative
size, nm
Exogenous
tryatsyl-
glycerol
Endogenous
triacylglycerol
cholester
ol esters
cholestero
l esters
Lipids
core
В-48, Сs,
Е, А-І, А-ІІ
В-100,
Cs, Е
В-100А-І, А-ІІ,
Е, Cs
lipoproteins
chylomicronsLPVLDLPLDLPHD
Major classes of lipoproteins
XM and VLDL - vehicles for transfer to tissue triacylglycerol, and LDL –
for carrying cholesterol to tissues, HDL - are responsible for reverse
cholesterol transport (for textiles). Fraction LPVH3 more active for reverse
cholesterol transport of tissues.

55. Cholesterol in Food
Cholesterol-rich foods, like
eggs, shrimp, and lobster
are no longer completely
forbidden.
Research shows that the
cholesterol we eat has only a
small effect on blood
cholesterol levels for most
people.
Daily cholesterol limits are 300
mg for healthy people and
200 mg for those at higher
risk.
One egg has 186 mg of
cholesterol.

56. Drugs with predominant effect on plasma total cholesterol and low
density lipoprotein cholesterol:
- Inhibitors of HMG-CoA reductase;
- Bile acid sequestrants;
- Probucol.
II. Drugs with predominant effect on the level of plasma
tryatsylahlitseryniv tryatsylahlitseryniv and very low density
lipoproteins
- Fibrates;
- Nicotinic acid;
- Polyunsaturated omega-3 fatty acids - eykozopentayenova
and dokozoheksayenova; maksepa.
Атеросклероз
Lipid lowering agents.
Lipid-lowering drugs should be taken for patients with life-time
detection of lipid metabolism. It is imperative that lipid-lowering
agents, lowering levels of LDL and VLDL in the blood, reduced to,
and better yet, improved antiatherogenic HDL levels.

57. Lipid lowering agents
Statins – inhibitors HMG-CoA
reductase
reduction of intracellular cholesterol concentration leads to an increase /
restore function of cell receptors for LDL, LDL cholesterol decreased by
25-40%, triglycerides - by 10-40%, and HDL - increased by 5-15%.
Lovastatin and Simvastatin - lipophilic
Pravastatin and Fluvastatin - hydrophilic
Lovastatin - taken from the fungus Aspergillus terrus
natural C
Atorvastatin - active in the initial state
Natural statins are only in the liver and peripheral
tissues reach

58. VII NATIONAL CONGRESS OF
CARDIOLOGY UKRAINE
Dose dependency:
10 mg - small doses
20-40 mg - average dose
80-100 mg - high doses
Effective average
doses of statins!
Therapeutic Cascade statins:
The first level of the therapeutic cascade: the
earliest action (weeks / months) → improved
endothelial function, reduced vascular
inflammation processes - the stabilization of
atherosclerotic plaques (vasodilation, "shrinkage")
The second level of the therapeutic cascade: stop
the progression of the old plaques and the
appearance of new, existing regression (30%!)
The third level of therapeutic cascade: reached
c / o 4 years or more since the beginning of the
application, to 18-30% reduced cardiac and total
mortality
• The fourth level of
therapeutic cascade: a
beneficial effect on
nekardialnu pathology - a
30% lower incidence of
diabetes, Alzheimer's
disease, vascular
dementia

59. Вихідний 6 місяців 12 місяців
Вихідний 6 місяців 12 місяців 12 місяцівВихідний 6 місяців
Results 12 month statin therapyResults 12 month statin therapy
T2-weighted magnetic resonance imaging (MRI)T2-weighted magnetic resonance imaging (MRI)

60. Атеросклероз
Fibrates.
• Practical significance
clofibrate, fenofibrate (lipantyn)
gemfibrozil, ufibrat.
Fibrates increase the activity of lipoprotein lipase and
thus accelerate the catabolism of VLDL, increase the
synthesis of LDL receptors, inhibit the formation of
VLDL in the liver.
In type III HLP, they are the drugs of choice.
Fibrates are used in daily doses of 300-400 mg to 2 g
•
May cause gastrointestinal tract, myositis, hepatitis,
cholelithiasis.The most common stones formed in the
gallbladder when using clofibrate.

61. - contain omega-3 and omega-eykozopentayenovu 3
dokozoheksayenovu acid.
taken at a daily dose of 2-3 g, which reduces the
formation of VLDL in the liver and to a reduction of
this class of lipoproteins in patients with type IV and
V HLP.
inhibit platelet aggregation, improve blood rheology.
The preparation of fish oil has proven to be an
effective mullion when combined
hipertryatsylhlitsernemiyi with hypercholesterolemia
(type IIb HLP).
Атеросклероз
Products of unsaturated fatty acids

62. 63
Consequences of
Obesity
Hippocrates
recognized that :
“sudden death is more
common in those who
are naturally fat than
in lean.”

63. 64
Treating Obesity
• Measure height and weight (BMI)
• Calculate waist circumference
• Assess comorbidities
• What labs does the patient need?
• Is the patient ready and motivated
enough to loose weight?
• Which diet should you recommend?
• Discuss a physical activity goal

65. 66
Weight Loss Strategies
• Diet therapy
• Increased Physical Activity
• Pharmacotherapy
• Behavioral Therapy
• Surgery
• Any combination of the above

66. 67
Rate Of Weight Loss
• A realistic goal is from 5% to 15% from baseline
in 6 months of obesity treatment.
• Weight should be lost at the rate of 1-2 lbs per
week, based on the caloric deficit between 500-
1000 Kcal/day.

67. 68

68. 69
Dieting
• Dieting is highly
ineffective - 95%
long term failure
rate
• Often results in
higher weight than
before the diet

69. WHAT AND HOW OFTENWHAT AND HOW OFTEN
You can eat in atherosclerosis?You can eat in atherosclerosis?
Meat - up to three times a
week.
Low-fat cheese, meat
and fish pies - once a week.
Homemade cakes, cookies or
cakes, dress-ted using
margarine or oil – twice a
week.
Potato chips or potatoes,
fried in butter – once every
two weeks.

70. 71
Principles Of Dieting
• Women should consume atleast 1200 kcal/day,
men 1500 kcal/day.
• Select a diet that has:
>75g/day proteins (15% of total calories)
> 55% total calories from carbs
▪ Fat should contribute 30% or less of total calories
Atleast 3 meals/day.
High fiber (20-30g/day), fruits and vegetables.
Supplement the diet with multivitamis and minerals.
Avoid sugar containing beverages and fat spreads.

71. What about all the diets that are out there?
How much does a diet
• Weight Watchers ($13 registration
fee, $15 weekly fee)
• Jenny Craig (consultation $200-370,
$65 meals/week)
• Tops Club ($20/week)
• Nutrisystem.com ($50/week) Atkins
Diet
72

73. Medications
A) Serotonin Nor-epinephrine Reuptake
Inhibitor: reduces food intake.
Sibutramine: initial dose 10mg/day, max
20mg/day.
B) Orlistat: Lipase inhibitor. Alters
metabolism, dec absorption of dietary fat.
120mg PO TID
74

74. Surgery
• Roux-en-Y gastric bypass.
• Lap band procedure
Criteria: a) BMI > 40 or >35 with 2 comorbidities.
b) Failure of non surgical methods
c) Presence of 2 or more medical
conditions that would benefit with weight loss.
75

77. Questions?