The document discusses the metabolic syndrome, including its definition, major features, epidemiology, pathophysiology, approach to diagnosis, and management. Regarding management, lifestyle modifications like weight loss through calorie restriction and increased physical activity are emphasized. Pharmacological treatments and metabolic/bariatric surgery may also be considered in some cases to treat individual components of the metabolic syndrome.

2. By :

3. o Introduction And Pathophysiology.
o Approach And Diagnosis.
o Management.

4. DEFINITION
• The metabolic syndrome (syndrome X, insulin resistance syndrome)
consists of a constellation of metabolic abnormalities that confer
increased risk of cardiovascular disease (CVD) and diabetes mellitus.

6. The Major Features Of The Metabolic Syndrome

7. EPIDEMIOLOGY
The prevalence of the metabolic syndrome varies around the world,
in part reflecting the age and ethnicity of the populations studied and
the diagnostic criteria applied. In general, the prevalence of the
metabolic syndrome increases with age
The highest recorded prevalence worldwide is among Native
Americans, with nearly 60% of women ages 45–49 and 45% of men
ages 45–49
Increases in waist circumference predominate among women,
whereas increases in fasting plasma triglyceride levels (i.e., to >150
mg/dL), reductions in HDL cholesterol levels, and hyperglycemia are
more likely in men.

10. • Many components of the metabolic syndrome are associated with a
sedentary lifestyle, Compared with individuals who watch television or
videos or use the computer <1 h daily, those who do so for >4 h daily have a
twofold increased risk of the metabolic syndrome

11. Central adiposity is a key feature of the syndrome, and the syndrome’s
prevalence reflects the strong relationship between waist circumference and
increasing adiposity. However, despite the importance of obesity, patients who
are of normal weight may also be insulin resistant and may have the metabolic
syndrome

12. Aging
The metabolic syndrome affects nearly 50% of the U.S. population
older than age 50, and at >60 years of age women are more often
affected than men. The age dependency of the syndrome’s prevalence
is seen in most populations around the world.

13. lipodystrophy

15. •Insulin Resistance The most accepted and unifying
hypothesis to describe the pathophysiology of the
metabolic syndrome is insulin
•Increased Waist Circumference
• Dyslipidemia
• Glucose Intolerance
• Hypertension
• Proinflammatory Cytokines
• Adiponectin

16. pathophysiology
A major contributor to the development of insulin resistance is an overabundance of
circulating fatty acids, released from an expanded adipose tissue mass. Free fatty acids
(FFAs) reduce insulin sensitivity in muscle by inhibiting insulin-mediated glucose uptake.
Increased level of circulating glucose increases pancreatic insulin secretion resulting in
hyperinsulinemia.
In the liver, FFAs increase the production of glucose, triglycerides and secretion of very low
density lipoproteins (VLDL). The consequences of this are the reduction in glucose
transformation to glycogen and the increased lipid accumulation in triglycerides (TG)
Insulin is an important antilipolytic hormone. In the case of insulin resistance, the increased
amount of lipolysis of stored triacylglycerol molecules in adipose tissue produces more fatty
acids, which could further inhibit the antilipolytic effect of insulin, creating additional
lipolysis
•

17. The adipose tissue of obesity exhibits abnormalities in the production
of several adipokines that may separately affect insulin resistance
These include increased production of inflammatory cytokines,
at the same time the potentially protective adipokine, adiponectin
are reduced

19. APPROCH TO THE
METABOLIC SYNDROME
BY:MOHAMMED ABDULBAST

20. 1- HISTORY
A careful history taking is important in metabolic syndrome.
it may be suspected if symptoms of any of the component disorders are present,
such as the increased hunger, thirst, or urination that may accompany
hyperglycemia or on medications .
Patients reporting a history of hypertension or on antihypertensive , dyslipidemia,
or hyperglycemia warrant screening for metabolic syndrome.
Symptoms suggesting the rise of complications, such as chest pain or shortness of
breath, must be investigated carefully.
As lifestyle changes can ameliorate the condition, attention should be paid to the
patient’s dietary habits and exercise routines so that areas for improvement can be
identified.
.

21. The social history is important .
A family history should be obtained because genetics may play an important role
in metabolic syndrome.
.
Finally, a thorough review of systems may help to identify related problems, such as
menstrual irregularities that can be seen in polycystic ovarian syndrome
The Metabolic Syndrome may give no symptoms .

22. 2- PHYSICAL EXAM
-1 waist circumference may be expanded
For male more than 100 cm and women more than 90 cm .

23. 2- BLOOD PRESSURE IS ELEVATED
Which is more than 130/85 mmHg

24. 3- SEVERE INSULIN RESISTANCE
 Acanthosis Nigerians , Hirsutism and Peripheral Neuropathy .

25. RETINOPATHY

26. RETINOPATHY

27. 4- SIGN OF SEVER HYPERLIPIDEMA
xanthomas or xanthelasmas

28. 5- SEVER ATHEROSCLEROSIS
arterial bruits

29. Associated diseases

30. CARDIOVASCULAR DISEASE
 The relative risk for new-onset CVD in patients with the metabolic
syndrome, in the absence of diabetes, averages between 1.5-fold
and threefold
 the Framingham Offspring Study (FOS)
 Patients with metabolic syndrome are also at increased risk for
peripheral vascular disease.

31. TYPE 2 DIABETES
 the risk for Type 2 diabetes in patients with the metabolic
syndrome is increased three- to fivefold.
 In the FOS’s 8-year follow-up of middle-aged men and women,
the population-attributable risk for developing Type 2 diabetes
was 62% in men and 47% in women.

32. NONALCOHOLIC FATTY LIVER DISEASE
Fatty liver is relatively common
 nonalcoholic steatohepatitis(NASH) both
triglyceride accumulation and inflammation coexist.
As the prevalence of overweight/obesity and the
metabolic syndrome increases, NASH may become
one of the more common causes of end-stage liver
disease and hepatocellular carcinoma.

33. HYPERURICEMIA
 Hyperuricemia reflects defects in insulin action on the renal
tubular reabsorption of uric acid, whereas the increase in
asymmetric dimethyl arginine, an endogenous inhibitor of
nitric oxide synthase, relates to endothelial dysfunction.
 Microalbuminuria also may be caused by altered endothelial
pathophysiology in the insulin-resistant state.

34. POLYCYSTIC OVARY SYNDROME
 PCOS is highly associated with the metabolic syndrome, with a prevalence
between 40 and 50%.
 Women with PCOS are 2–4 times more likely to have the metabolic syndrome
than are women without PCOS.

35. OBSTRUCTIVE SLEEP APNEA
• OSA is commonly associated with obesity, hypertension,
increased circulating cytokines, IGT, and insulin resistance.
• Moreover, when biomarkers of insulin resistance are compared
between patients with OSA and weight-matched
controls, insulin resistance is more severe in patients
with OSA.
• Continuous positive airway pressure (CPAP)
treatment in OSA patients improves insulin sensitivity

36. Diagnosis

37. THE DIAGNOSIS OFTHE METABOLIC SYNDROME RELIES ON SATISFYING
THE CRITERIA LISTED BELOW :

38. LABROTORY
1- fasting glucose …..….Which is more than 100 mg/dl
2-Fasting lipids ……..Triglyceride level above 150 mg/dl
low HDL level for M below 40mg/dl
for F below 50mg/dl
are needed to determine if the metabolic syndrome is present .

39. ADDITIONAL LAB
 In the presence a family history of early coronary or other atherosclerotic
disease Do additional test to HDL-C like
 1- low-density lipoprotein cholesterol (LDL-C)
 2-studies of lipoprotein(a),
 3- apolipoprotein-B100,
 4- high-sensitivity C-reactive protein (CRP)
 5- homocysteine and fractionated LDL-C.

40. ADDITIONAL LAB
 In view of the various aspect between metabolic syndrome and associated
conditions, additional helpful blood tests may include :
 1- thyroid function test , Increased thyroid stimulating hormone (TSH) has been
linked to a higher prevalence of metabolic syndrome
 2- liver function test for (NASH)
 3- renal function test … microalbuminuria
 4- hemoglobin-A1C levels , for diabetic pt. follow up

41. ADDITIONAL LAB
 5- uric acid level , Hyperuricemia appears to be much more common in patients with metabolic
syndrome than in the general population, and this is attributed to the inflammatory effects of
metabolic syndrome.
 6-prothrombotic factors (fibrinogen, plasminogen activator inhibitor 1)
 7-PCOS is suspected on the basis of clinical features and anovulation, testosterone, luteinizing
hormone, and follicle-stimulating hormone should be measured.

42. IMAGING STUDIES
 Imaging studies are not routinely indicated in the diagnosis of metabolic
syndrome.
 hey may be appropriate for patients with symptoms or signs of the many
complications of the syndrome, including cardiovascular disease.
 (IHD)chest pain, dyspnea, or claudication may warrant additional testing with
electrocardiography (rest/stress ECG), ultrasonography (vascular or rest/stress
echocardiography), stress single-photon emission computed tomography
(SPECT), cardiac positron emission tomography (PET),
Cardiac Syndrome X?!

43. TESTING FOR SLEEP-RELATED BREATHING DISORDER
Polysomnography ….. Is multi parametric test in the study of
sleep which is diagnostic tool in sleep medicine.
 it`s monitoring many body function like:
 1- Brain by EEG
 2- Muscle activity by EMG
 3- Heart rhythmus by ECG
 4- breathing function by Peripheral PULSE OXIMETER

44. POLYSOMNOGRAPHY

47. Obesity is the driving force
behind the metabolic
syndrome.
Thus, weight reduction is the
primary approach to the
disorder.
With weight reduction,
improvement in insulin
sensitivity is often
accompanied by favorable
modifications in many
components of the metabolic
syndrome.

49. In general, recommendations for weight loss include a combination of:

50. Caloric restriction
o Is the most important component,
o whereas increases in physical
o activity are important for
o maintenance of weight loss.
o Some but not all evidence
o suggests that the addition of
o exercise to caloric restriction
o may promote greater weight loss from the visceral
depot.
o The tendency for weight regain after successful weight
reduction underscores the need for long-lasting
behavioral changes.

51. Before prescribing a weight-loss diet, it is important to
emphasize that it has taken the patient a long time to
develop an
expanded fat mass; thus, the correction need not occur
quickly.
Given that ~3500 kcal = 1 lb of fat, ~500-kcal restriction daily
equates to weight reduction of 1 lb per week.
Diets restricted in carbohydrate typically provide a rapid initial
weight loss.
Diet

52. However, after 1 year, the amount of weight
reduction is minimally reduced or no different
from that with caloric restriction alone.
Thus, adherence to the diet is more important
than which diet is chosen.
Moreover, there is concern about low-
carbohydrate diets enriched in saturated fat,
particularly for patients at risk for CVD.
Therefore, a high-quality dietary pattern—i.e., a
diet enriched in fruits, vegetables, whole grains,
lean poultry, and fish—should be encouraged to
maximize overall health benefit.

53. Physical Activity
Before a physical activity recommendation is
provided to patients with the metabolic
syndrome, it is important to ensure that the
increased activity does not incur risk.
Some high-risk patients should undergo
formal cardiovascular evaluation before initiating an
exercise program.
For an inactive participant, gradual increases in physical
activity should be encouraged to enhance adherence and
avoid injury.
Although increases in physical activity can lead to modest
weight reduction, 60–90 min of daily activity is required to

54. Even if an overweight or obese adult is unable to undertake this
level of activity, a significant health benefit will follow from at
least 30 min of moderate-intensity activity daily.
The caloric value of 30 min of a variety of activities can be
found.
Of note, a variety of routine activities, such as gardening,
walking, and housecleaning, require moderate caloric
expenditure.
Thus, physical activity need not be defined solely in terms of

55. Behavior Modification
 Behavioral treatment typically includes
recommendations
for dietary restriction and more physical activity,
resulting in weight loss that benefits metabolic
health.
 The subsequent challenge is the duration of the
program because weight regain so often
follows successful weight reduction.
 Long-term outcomes may be enhanced by
a variety of methods, such as the Internet, social
media, and telephone follow-up to maintain contact
between providers and patients.

57. In some patients with the metabolic syndrome,
treatment options need to extend beyond lifestyle
intervention.
Weight-loss drugs come in two major classes:

58. Appetite suppressants
approved by the U.S. Food and Drug Administration
include phentermine
(for short-term use [3 months] only) as well as the more
recent additions phentermine/topiramate and
lorcaserin, which are approved without restrictions on
the duration of therapy.
In clinical trials, the phentermine/topiramate
combination has resulted in ~10% weight loss in 50%
of patients.
Side effects include :
palpitations, headache, paresthesias, constipation, and
insomnia.
Lorcaserin results in less weight loss—typically ~5%
beyond placebo—but can cause headache and

59. Absorption Inhibitors
Orlistat inhibits fat absorption by
~30% and is moderately
effective compared with placebo
(~5%more weight loss).
This drug is often difficult of take
because of oily leakage per
rectum.

60. Diuretics and ACE inhibitors may be used to
treat hypertension.
 Cholesterol drugs may be used to lower LDL
cholesterol and triglyceride levels, if they are
elevated, and to raise HDL levels if they are
low.
Use of drugs that decrease insulin resistance,
e.g., metformin and thiazolidinediones, is
controversial; this treatment is not approved
by the U.S. Food and Drug Administration
The most probable benefit was to triglyceride
levels, with 43% showing improvement; but
fasting plasma glucose and insulin resistance
of 91% of test subjects did not improve.

61. The combination preparation simvastatin/sitagliptin (marketed
as Juvisync) was introduced in 2011 and the use of this drug was
to lower LDL levels and as well as increase insulin levels. This
drug could have been used to treat metabolic syndrome but was
removed from the market by Merck in 2013 due to business
reasons.
High-dose statins, recommended to reduce cardiovascular risk,
have been associated with higher progression to diabetes,
particularly in patients with metabolic syndrome. The biological
mechanisms are not entirely understood, however, the plausible
explanation may lie in competitive inhibition of glucose
transport via the solute carrier (SLC) family of transporters
(specifically SLCO1B1), important in statin pharmacokinetics.

63. Metabolic or bariatric surgery
is an option for patients with the metabolic syndrome who
have a body mass index >40 kg/m2, or
>35 kg/m2 with comorbidities.
An evolving application for metabolic surgery includes
patients with a body mass index as low as 30 kg/m2
and type 2 diabetes.
Gastric bypass or vertical sleeve gastrectomy results in
dramatic weight reduction and improvement in the features
of the metabolic syndrome.
A survival benefit with gastric bypass has also been realized.