Sinergy !

University in Beograd
Sinergy ! University in Beograd
Resons to take these action-study
The social and scientific importance of
sindrom X is in root of global epidemic of
hronic noncomunicable diseases (HNCD),
specially Cardiovascular diseases and
Diabetes melitus type 2, in wich ethioptho-
genesis atherosclerosis play central role
and/or there is glukoregulation disturban-
cies.
cies

 Thesse diseases are linked with obesity,

atherogenic dislipidemia and physical
inactivity.

 Economic reasons are so important

because (1:10 is proportion of prices of
Sinergy !and their terapy)
prevention University in Beograd
How we became in situation of global epidemy
of HNCD and did not seen hight atherogenic
potential of Syndrom X ?
 Price and unsutible technik of insulin euglicaemic
clam for population measurments of insulin sensitivity
andi parcial view of investigation of so much complicated
problem, than:

 General view that factors of Syndrom X are not

linked each-other or with IR, nor phynctionaly, nor
methabolicaly. But,

 aterosklerotic proces
In 1985. is find that
is reversibile (AT) and was accented the
importance of egzogenic risico faktors
like: stress, obesity, unsuitible nutrition
i specialy physical activity.
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 Results of past investigation
 Since 1990 y. up 2002. Sindrom X is mainly investiga-
ted in cross sectional studies and factor analisys, but…..

 Epydemiologist from Bristol, UK (Lawlor Debora and

co-worers, in 2004 made big meta-analisys of 22 studies
which were performed in past 15 years on world plan,
and they find that for understanding of pthophysiology of
Sindrom X is necesarry longitudinal (longterm) studies,
and multidisciplinar coloboration of: physiologists, biche-
mists, specialist for nutrition, for physical activity and
endocrinologist.

In 1996 y, Flier-a S. Say that :

“ Insulin resistance became firmly investigated
object of basical and clinical investigation, it growth up
more and more than is thin domen of clinical
dijabetology, where
these concept was born before 60 years " …… J.S. Flier
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  Elimination of o
verweight body
mass and/or ob
esity is importa
for elimination nt
of Syndom X, b
is not sufficient ut it
fot all patien wit
Syndrom X, bec h
ause........
 nor all o
verwigh has Sy
nor all thiny pe X and IR,
rsons are health
and they can to ,
have IR and/o
Syndrom X r

(Freendland, S 2
004; Cefalu W,
2 00 2)

Sinergy ! University in Beograd

Author, M.Vidin, 2004 god.
Criteria for diagnosis of Sy X from 1998. (Alberti KG, 1998.)
and Criteria for obesity,1997. ( WHO, 1997 ) include:

 Signs (parameters) of glukoregulation

homeostasis:
1. levels of glucoregulation disturbancies
2. parameters of insulin sensitivity

 signs (parameters) of plasma lipids:

1. HDL-cholesterol i
2. tryglicerides,

 antopometrical signs (parameters) of

1. overweight and obesity and
2. parameters of abdominal and / or visceral obesity…..

These way permit investigation of

pathSinergy
ophysiology
! and therapy ofUniver
sindroma
sity inXBeograd
.
there were big knoledge of influence of foodm
physical activity, stress and bichevioral therapy,
but there was not hypothesis of

PATHOPHYSIOLOGY OF SYNDROM X,

Definition of World health organisation (WHO),

1997y. for body weight clasification and criteria
from 1998y. for syndrom X ( Sy X ) give a chance
to define pathophysiology of Syndrom X ....
Useful facts that can be mached were come from East
and from West, sourcelly: Reaven Gerald 1972, 1988
and 2005, Dilmjan Vladimir, 1974; than Stern M,1989;
Krier F, 2004; Freendland E, 2002; Alberti KG, 1998;
Cefalu S, 2000; Chan U, 2004 ; Katz A, 2000 ;
Lawlor D, 2004 ; Hanley M,1998 i Meigs S, 2000,
and new others......
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Linkage beetween chronic non comunicable diseases (HNCD),
insulin resistance and some athergenic risico factors (ATRF)

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Procents of some CVD in general rate of death
from CVD in USA-in 1999 year

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Clasification of atherosclerosis stage
(Apollo lipids,Edu.sci,2005)

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Pathomorphological aterosklerotic aorte disturbances :
mild, midle, strong (Apollo lipids, Edu. sci, 2005)

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Clasification of atherogenic risiko factors (ATRF), their origine
and possibility of their elimination (Vidin M,1998)

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Clasters and syndroms with hight atherogenic potential

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Prevalence of atherogenic risico factors in patient with
syndrom X (Stern M, Ferrarini E, 1991)

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Dijagnostic criteria of varies syndroms with
Insulin resistance Bloomgarden TZ,2004

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Sinergy ! University in Beograd
Link beetwen insulin resistane, growth hormon and
somatostatin in answer to stresss (Dilmjan V,1974)

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 Stress, symphatoadrenal axis and
Hypothlamo-hypophyeo-medular axis

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 Clasification of glucoregulation disturbancies according :
American organisation for diabetes and WHO
(ADA, 1997 i WHO,1998)
Proportion of conc.
of insulin and conc.
of growth chormon
in Syndrom X
Hyperinsulinaemia
cannot regulate
hyperglicaemic state
because Free Faty
Acids (FFA) block
insulin action and
Has the main role.
Concentration of
plasmatic Growth
chormon (STH)
is lower because
somatostatin blok
secretion of STH .
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DM yipe 2=secretion of
insulin is lowered
Criteriums of stage of nutrition (WHO, 1997)

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 Qualification of insulin sensitivity
1. IS index - hyperglicaemic ins. slamp
2. Minimod IS index-hyperglicaemic ins.
slamp
=Gold standard for all form of IR, specially for IR with
pathomorphological basis, but problem is a lot of samples
IRand difficult count
in Syndrom X - linked with elevated Other indexes of insulin
sensitivity
visceral fat and general obesity
1. HOMA indeks
HI=[log(Io)+log(Go)]
1. QUICKI INDEKS (Katz,2000) 22,5
QI= _____1__ _______ fasting insulin ( μIU/L)
fasting glucose (mmol/L)
[log(Io) + log(Go)] 2. Ln HOMA index
3.Benet index
2. IS-FFM indeks (uzima u obzir veličinu mršave
telesne mase i kon. Triglicerida u plazmi)
IS (FFM) Sinergy ! ins. našte − 0,31 (fasting TG)]University in Beograd
=e [ 2,63 − 0,28x(log.
Aterogeniq potential and composition
of lipoprotein bodies

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Structure of lipoprotein
body (Biomerieux,1987)

Differences in amount of
cholesterol and triglycerides
in hylomicrones and in HDL
bodies
(Biomerieux,1987)

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 Syndrom X (SY X) risico factors:

Up today known risico factors resposible for

Syndrom X are:
1. Overaeting generaly (biger caloric intake),
2. Overconsumption of carbochydrates and
or saturated fat generaly,
3. Abdominal obesity,
4. Disturbancies of diurnal rhitmus ( WRONG
DIETARY STYLE AND LIFE STYLE),
5. LOWERED DEILY PHYSICAL ACTIVITY,
6. Alckohol consumtion
7. EFFECTS OF SUBCHRONIC STRESSORS

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 PHYSIOLOGY OF SYSTEMS FOR
REGULATION OF ENERGETIC BALANCE

1. Dnevna energijska potrošnja organizma

a. Bazalna metabolička potrošnja – BMR
b. Termalni efekat hrane
c. Fizička aktivnost
Izračunavanje bazalne metaboličke potrošnje BMR na osnovu
veličine telesne mase prema polu i starosti, prema SZO
osobe od 18 do 25 godina starosti
muškog pola BMR = 15,3*TM + 679
ženskog pola BMR = 14,7*TM + 496
osobe od 30 do 60 godina starosti
muškog pola BMR = 11,6*TM + 879
ženskog pola BMR = 8,7*TM + 829
2. Mrko masno tkivo i neurohumoralni
mehanizmi fakultativne termogeneze
(dijetom inducirana termogeneza (DIT))
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 ADAPTIVE MECHANISMUS FOR
STABILE BODY WEIGH

1. REGULATED FORM OF KEEPING

AMOUNT OF FAT BODY MASS

2. NON REGULATED FORM OF KEEPING

AMOUNT OF FAT BODY MASS

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Regulation of energetic homeostasis and
Apetit control - Modern concepts

Regulation of energetic methabolism and apetit control

go with neurohormonal circuits, and concept of isolated
centers is now past (Wynne Katty, 2005)

NARC (nukleus arkuatus), apety control

Hypothalamic nuclei of “ sekcija korona ”

Central kontrol of a apety

Perifern kontrol of apety

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Hypothlamic nuclei of “ sectia korona ”
(Wynne K, 2005).

Eminencija mediana

Abbrevations:
Sinergy ! Univer
NPY,-neuropeptid gama; GHS-R, receptor sekretagoga hormona sit
rasta;
aguti relatirani peptid,CART- cocain, amfetamin relatirani transkript
y inmelanostimulirajući
αMSH, Beograd hormon; AgRP-
 Apetit control, NARC (nukleus arcuatus),
(Wynne K, 2005)

Treća
komora

Abbrevations: –MSH ,-melano-stimulirajući hormon; GHS-R, receptor

sekretagoga hormona rasta; BDNF- moždano neurotropni faktor (eng. brain-
derived neurotrophic factor);CRH -kortikotropni rilizing faktor (eng.-
corticotrophin-releasing hormone; MCH, melanosti-mulirajući hormon (melanin-

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concentrating hormone);ME,eminencija medijana (eng. median eminence); PFA,
periforni-kalna zona (eng. perifornical area);TRH, tirotropin oslobađajući hormon
(eng. thyrotropin-releasing hormon),
 Central control of apetit (Wynne K, 2005)

Abbrevations: :
-AP, area postrema ; ME: eminencija medijana (eng. median eminence);
NAC, nukleus akumbiens (eng. nucleus accumbens);
PFA, perifornikalna area (eng. perifornical area)
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NTS, nukleus traktus solitarius(eng. nucleus tractus solitarius) in Beograd
Periferal apetit control, (Wynne K, 2005)

abbreviation
s
1. GH-relin
2. Adiponektin
3. Leptin
4. Rezistin
5. Insulin
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6. Peptid-y
7. YY3-36
Hypothalamus, neuroendocrine regulation and homeostsis of
energo-methabolic spending (Diagnostic Systems Laboratory, Inc.)

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DISTURBANCIES OF HOMEOSTASIS of ENERGO-METABOLIC
BALANCE AND ETHIOPTHOGENESIS OF SYNDROM X

Bodily source of glucolysis

1. Egzogenic glucose – with food
2. Endogenic source of glucose

Posibility of glucose methabolismus -

Energo-methabolic utilisation of glucoze
a) oxidation of glucoze
b) transfering in lipides
c) transfering in other carbo-hydrates and
nonesentional fatty acids

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Lipid apsorbcion and production of chylomicrones
(Biomerieux, inc)

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 ANTIATHEROGENIC EFEKTS OF HDL-LP

Liver secret HDL-lp and they get cholesterol from

arthery walls and transfer it trought bllader in colon
Sinergythem.
and excrete ! Universitcan
(but cholesterol, y in Beograd
be recycled if
 Patways of cholesterol: excrecion trought
goldbllader in digestive

liver

goldbllader
HDL transport of
intracelular
holesterol
Illeus,
colon

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Secretion of VLDL from liver: cholesterol go on arthery
waals but tryglicerides from blood go in visceral and
other fat depos

Tryglicerides go
in abdominal
fat depoes
liver
Cholesterol is transport
on arthery walls

VLDL-LP

LDL-LP i IDL REMNANTS

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 Functional and morphologyc diferences of cells of
subcutaneus and visceral intraabdominal fat
( Freedland SE, 2004 i Wajcenberg BI,2000)

VAT (visceral adipose tisue) SCAT(subcutaneus

1. Main predictor of Syndrom of IR adipose tissue)
2. No answer on insulinogenic
adipogenic efects 1. preadipociti have biger
3. Easy go in lypolysis kapacy of diferencijation
4. portal drenage
5. It can to elevate lipolysis of 2. They can go in VAT tissue
SCAT
6. It produce more inhibitor 3. estrogen ga promoviše
plazminogena aktivator and IL-6 (glutealno, posebno)
7. Has more glukokortikoid
receptors 4. produce leptin
8. The density of androgenic
receptor is biger 5. Has protect role in proces of
insulin resistance IR

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Cholesteril ester transfer protein (ECTP) and his
Importance for activyty of HDL lipoproteins

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Methabolismus of hepatal lipids and
lipogenesis " DE NOVO ” (Donnelly KL et al., 2005).

”DNL"

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Insulin and glucose influence on sintesis of aktivators of
" lipogenesis de novo " (DNL), which give elevated
production of triglicerides in liver and insulin resistance

(Tamura S, 2005)

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Influence of Free Faty Acids (FFA) on neuroendokrine regulation and
deposit of lipids on predilektion places: in liver, in muscules, on endotel
of blood vesels waal or on dorsal ganglion of spine

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Etiological clasification of obesity
(Bray G,1989)

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Morphologic characteristic and funkcional klasification
of elevated fat-body mass accord. Claude Boushard

tip 1: Generally overweit body mass,

fat tissue is generally over

tip 2: Android typ of obesity,

ellevated subcutaneous fat
predilection is upper choulder, back (SCAT)

tip 3: Abdominal-visceral type,

elevated fatis in visceral depots (omentum majus,
ommentum misus ie. ligg. abdominalis, eng. visceral
adipose tissue (VAT))

tip 4: Gynoid typ of obesity

predominant elevated gluteofemoral fat .

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Elimination of tresch intraabdominal
fat and keeping of insulin sensitivity

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 Main reactions of neuroendocrine sistem
in alarm phase

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Integrated prescription for physical activity for
health and cardiorespyrthory fitnness

Sinergy ! University in Beograd