2. “Metabolic Syndrome”
A cluster of signs & symptoms associated with cardiovascular
and cancer risk [1&2].
The term dates from the 1950’s but the clustering has been
known since the 1930’s [1].
The contemporary interest began with Dr Gerald Reaven’s
1988 Banting Lecture [3].
Doctors have debated whether it is a “disease”
1. Phillips GB : Am J Med 1978 2. Grundy SM : J Clin Endocrinol Metab 2004
3. Reaven GM : Diabetes 1988
3. Metabolic syndrome is also known as:
Metabolic syndrome X
Cardiometabolic syndrome
Deadly quartet
Syndrome X
Insulin resistance syndrome
Reaven's syndrome (named for Dr. Gerald Reaven)
CHAOS (in Australia): Coronary artery disease,
Hypertension, Adult onset diabetes, Obesity, and Stroke
Das UN : Curr Hypertens Rep 2004
4. HOW TO DEFINE METABOLIC
SYNDROME?
prominent
characteristics of the
metabolic syndrome
1. Cardiovascular risk factor
2. Elevated LDL- cholesterol
3. Insulin resistance (WHO*)
4. Atherogenic dyslipidemia
(aprothrombotic state)
5. Hypertension
6. Abdominal obesity
7. Elevated levels of various
inflammatory markers
(NCEP&WHO)
8. Central obesity (IDF)
5. Alberti KG et aI :Diabetes Med 1998
6. Grundy SM et aI :Circulation 2005
7. Haffner SM : Am J Cordial 2006
8. Kim SH et al : Diab Vasc Dis Res 2004
5. Metabolic syndrome: “Harmonized”
definition (2009)
PARAMETER:
WAIST CIRCUMFERENCE
TRIGLYCERIDES (MG/DL)
HDL-C (MG/DL)
BLOOD PRESSURE
FASTING GLUCOSE (MG/DL)
ORAL GLUCOSE
TOLERANCE TESTS
LIMIT VALUES:
POPULATION SPECIFIC
> 150
MEN: < 40; WOMEN: <50
>130/>85
> 100
Zaki M, et al. Open Access Maced J Med Sci. 2017 Jun 15; 5 (3): 275-280.
6. Different Percentage of Metabolic Syndrome in continents
Tabatabaie et al: Diabetes & Met 2015
Ehrmann DA, et al. The Journal of Clinical
Endocrinology & Metabolism. 2006.
Angelo Scuteri: peiventive cardiology 2014
Earl S. FORD: Journal of Diabetes 2010
7. Aging Effects on Prevalence
Tabatabaie et al: Diabetes & Met 2015
9. The Continuum of CV Risk in metabolic
syndrome
Georgiopoulos G, et al. Atherosclerosis. 2016.
10. A fasting triglyceride value of <150 mg/dL is
recommended. a weight reduction of >10% is necessary to
lower fasting triglycerides.
A fibrate (gemfibrozil or fenofibrate) is the drug of
choice to lower fasting triglycerides and typically
achieve a 35–50% reduction.
Other drugs that lower triglycerides include statins,
nicotinic acid, and high doses of omega-3 fatty acids.
TRIGLYCERIDES
Georgiopoulos G, et al. Atherosclerosis. 2016.
11. For rise in HDL cholesterol, weight reduction is an
important strategy.
Nicotinic acid is the only currently available drug with
predictable HDL cholesterol-raising properties.
Statins, fibrates, and bile acid sequestrants have
modest effects (5–10%), and there is no effect on HDL
cholesterol with ezetimibe or omega-3 fatty acids.
HDL Cholesterol
Georgiopoulos G, et al. Atherosclerosis. 2016.
12. LDL Cholesterol
For patients with the metabolic syndrome and
diabetes, LDL cholesterol should be reduced
to <100 mg/dl.
Georgiopoulos G, et al. Atherosclerosis. 2016.
13. BLOOD PRESSURE
• The direct relationship between blood pressure and
all-cause mortality rate has been well established.
• Best choice for the first antihypertensive should
usually be an angiotensin-converting enzyme (ACE)
inhibitor or an angiotensin II receptor blocker.
• In all patients with hypertension, a sodium-restricted
diet enriched in fruits and vegetables and low-fat
dairy products should be advocated.
Soler A, et al. The FASEB Journal. 2016
14. Insulin resistance is the primary Patho-physiologic mechanism for the
metabolic syndrome.
Several drug classes [biguanides, thiazolidinediones (TZDs)] increase
insulin sensitivity.
Both metformin and TZDs enhance insulin action in the liver and
suppress endogenous glucose production. TZDs, but not metformin, also
improve insulin-mediated glucose uptake in muscle and adipose tissue.
Benefits of both drugs have also been seen in patients with NAFLD and
PCOS, and the drugs have been shown to reduce markers of
inflammation and small dense LDL.
INSULIN RESISTANCE
Sangaleti CT, et al. The FASEB Journal. 2016
15. In patients with the metabolic syndrome and Type 2 diabetes,
aggressive glycemic control decreases cardiovascular risk..
In patients with IFG without a diagnosis of diabetes, a lifestyle
intervention has been shown to reduce the incidence of Type 2
diabetes.
Metformin has also been shown to reduce the incidence of
diabetes, although the effect was less than that seen with
lifestyle intervention.
GLYCEMIC CONTROL
Sangaleti CT, et al. The FASEB Journal. 2016
16. Most patients with metabolic syndrome exhibit a prothrombotic state
characterized by elevations of plasminogen activator inhibitor-1 and
fibrinogen.
Use of low dose aspirin can be recommended for patients with
metabolic syndrome, who have a high CV risk, those with overt type 2
diabetes mellitus, or atherosclerotic cardiovascular diseases.
Metabolic syndrome frequently is accompanied by a pro-inflammatory
state, characterized by increased CRP levels. No specific treatment
available.
Prothrombotic & Proinflammatory State
Mauras N et al,The Journal of Clinical Endocrinology & Metabolism. 2010.
18. PHYSICAL ACTIVITY
60–90 min of daily activity (At least 30 min.) Gradual increases in
physical activity should be encouraged to enhance adherence and avoid
injury.
Some high-risk patients should undergo formal cardiovascular evaluation
before initiating an exercise program.
Physical activity could be formal exercise such as jogging, swimming, or
tennis or routine activities, such as gardening, walking, and
housecleaning.
Rao DP, et al, International Journal of Behavioral Nutrition and
Physical Activity. 2016.
19. Decreased Activity decreases Insulin
Sensitivity
Increased post-meal glucose
levels and more variability in
24-hour levels from lowest
to highest concentrations
Furukawa S, et al, The Journal of clinical investigation, 2017.
20. AT is more
effective than RT
or however the
combination of
these two training
was effective still
not more than AT
alone.
Touati
2011
Grazioli
2017
Matsuo
2015
Lori
2011
Physical activity & metabolic
syndrome
PA promises to be
an important tool
to be used alone
or in combination
with traditional
therapies to
improve disease
prevention and
treatment
Either HIIT or
MICT has a positive
effect on metabolic
risk factors however
HIIT improve CRC
more
Exercise training
includes beneficial
effects without
the requirement
for dietary
modification
21. Tomohiro Okura et
al 2007:
Effects of
Exercise on Met
S Improvement
is in Response to
Weight
Reduction.
Disagreements
S.Baldocci et al
2010:
Improvement
Effects of
Exercise on MetS
is dependent on
training
modification &
independent of
weight loss.
23. Name Year Journal Conclusion
Nicole O.
McPhers
2015
J Physiol Endocrinol
Metab
Diet: founder males restores insulin
sensitivity and normalized adiposity in
female offspring
Buscemi S 2013
Er J Clin Nutr
u
The effects of a Mediterranean diet
upon cardiovascular health have been
extensively reported in adults
Arora T 2015 Int J Obes (Lond)
young adolescents with greater BMI
had poorer dietary habits
Nora E.
Straznicky
2010 Diabetes
sympathetic neural adaptation to a
hypocaloric diet cause weight loss
regardless of adding moderate-intensity
aerobic exercise
Diet and MetS
25. Weight reduction- include a combination of caloric restriction,
increased physical activity, and behavior modification.
LIFESTYLE MODIFICATIONS
26. ~500 kcal restriction daily equates to weight reduction of 1 lb per week.
Diets restricted in carbohydrate typically provide a rapid initial weight
loss.
Adherence to the diet is more important than which diet is chosen.
A high-quality diet— i.e., enriched in fruits, vegetables, whole grains, lean
poultry, and fish—should be encouraged to provide the maximum overall
health benefit.
DIET---
Kawada T. The Journal of pediatrics. 2016.
27. Decrease:
• risk of thrombosis
• plasma homocysteine
concentration
• decrease in body fat
Improvements:
•In the blood lipid profile
•endothelial function
•insulin resistance
Mediterranean Diet
Yang J, et al. PLoS One. 2014.
28. Substrate mixture matters:
Obesity 19(4), 676–686 (2011)
“...the substrate mixture oxidized must be equivalent, on
average, to the composition of the nutrient mix
consumed.”
That means:
If one consumes a diet higher in fat, one must also
metabolize fat at a higher rate.
Kawada T. The Journal of pediatrics. 2016.
Kawada T. The Journal of pediatrics. 2016.
29. Lose weight
oLosing as little as 5 to 10% of your body weight can reduce insulin levels and
high blood pressure, thus reducing your risk of diabetes.
Exercise
oWalking just 30 minutes a day or engaging in other aerobic activities can help
prevent the serious diseases associated with MS.
Stop smoking
oSmoking cigarettes increases insulin resistance and worsens health
consequences associated with MS.
Eat fiber-rich foods
oWhole grains, beans, fruits and vegetables are high in dietary fiber. These are
important foods to eat since dietary fiber is known to lower insulin levels.
Although metabolic syndrome creates a real risk for developing
diabetes, stroke or heart disease, these conditions can be prevented.
Insulin resistance can be controlled by the following:
Magge SN, et al. Pediatrics. 2017:e20171603.
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