SINDROMEMETABOLICO SINDROMEMETABOLICO

DR.CARLOSA.ROCHARODRGUEZ MEDICOINTERNISTA
24DEFEBRERO2011

 Metabolicsyndromeasasyndromeremains

controversial,thetermcontinuesto effectively alertclinicianstoanimportant patientphenotype . Multipleclinicaldefinitionsofthemetabolic syndromehavebeenproposedoverthepast 11years. Themetabolicsyndromeremainsunder recognized, underdiagnosed,and undertreated.
CurrOpininCardiol2010, 25:502512

 Metabolicsyndrome(MS)isaclusterof

severalcardiometabolicriskfactors, metabolicriskfactors, includingabdominal includingabdominalobesity,hyperglycemia, dyslipidemiaandelevatedbloodpressure.

SaludPublicaMex2010;52suppl1:S11S18

 PrevalenceofMSinMexicanadultswas26.6%in

1993(ATPIII). MetabolicsyndromeprevalenceamongMexican adultsaccordingtoATPIII,AHA/NHLBIandIDF, was36.8%, 41.6%and49.8%,respectively. (20052006)ENSANUT2006. 2006)ENSANUT2006. Women weremoreaffectedthanmenusingany ofthethreedefinitions,explainedinpartbythe higherprevalence ofcentralobesity.
SaludPublicaMex2010;52suppl1:S11S18

 Themetabolicsyndromeprovidesthe

epidemiologistaninstrumentwithastrong predictivepowerandtheprimarycare physician. IdentifyingMSprovidesausefultoolfor planningpublichealthpolicies. ATPIIIcriteriaidentifiespatientsatriskof developingCHDwitharelativeriskof2.7and of5.9forincidentdiabetes of5.9forincidentdiabetes.

Salud PublicaMex2010;52suppl1:S11S18

Fisiopatologa Fisiopatologa

J.Clin.Invest.2006: 116;17841792

AdverseEffectsofAlterationsin AdverseEffectsofAlterationsin CircadianRhythms Clockgenedisruptiontargetedtothefatbodyis sufficienttoinduceincreasedfoodconsumption, decreasedglycogenlevels,andincreased sensitivity tostarvatio tostarvation. Humanstudiesdemonstratesrhythmicvariation inglucosetoleranceandinsulinactionacrossthe daybut arenotwellunderstoodthemolecular mechanisms.

CircRes.2010;106:447462

AdverseEffectsofAlterationsin AdverseEffectsofAlterationsin CircadianRhythms

Cardiovasculardiseaseandhypertensionare Cardiovasculardiseaseand

alsoassociatedwithsleeploss:theriskofa fatalheartattackincreases45%inindividuals whochronicallysleep5hourpernightorless Numerouscoagulation/fibrinolyticfactors, suchasproteinC,antithrombin,factorVII, proteinS,andfibrinogen,havebeen demonstratedtofluctuateinacircadian mannerinhumans.

CircRes.2010;106:447462

Fisiopatologa
Adiponectin PAI1Resistin 1Resistin FNTalfaAngiotensinogen alfaAngiotensinogen LeptinLPL IL1,IL2,IL6Complement 6Complement Adipocyte IGF1Visfatin 1Visfatin TGFBBindingproteins BBindingproteins QuimerinaFFA Retinolbindingprotein4
CastroMG,GodinezSA,LiceagaG.Temasselectosenmedicinainterna2010. Obesidad,grasavisceraleinflamacin.1Ed.MxicoColegiodeMedicinaInterna deMxico2010pp.163178

Factoresdegrasavisceral

CastroMG,GodnezSA,LiceagaG.Obesidad.Funcinydisfuncindeltejido adiposo,1Ed.Mxico adiposo,1Ed.MxicoColegiodeMedicinaInternadeMxico2009pp.39 51

Fisiopatologa

CastroMG,GodnezSA,LiceagaG.Obesidad.Funcinydisfuncindeltejido adiposo,1Ed.MxicoColegiodeMedicinaInternadeMxico2009pp.39 adiposo,1Ed.MxicoColegiodeMedicinaInternadeMxico2009pp.39 51

Adipocitocinas
Citocina Adiponectin Leptin Resistin Visfatin Retinolbinding protein4 TNFAlfa IL6 Angiotensinogen Plasminogenactivator inhibitor1(PAI1 VisceralFat ++ + ? ++ + + ++ ++ ++
SubcutaneousFat Expressionin Obesity Effecton InsulinSensitivity

+ ++ ? + ++ ++ + + + ? ? =

CurrentPharmaceuticalDesign2007:13;21482168

Fisiopatologa

CastroMG,GodnezSA,LiceagaG.Obesidad.Funcinydisfuncin deltejidoadiposo,1Ed.MxicoColegiodeMedicinaInternade Mxico2009pp.39 51

Fisiopatologa Fisiopatologa

EndocrineReviews,December2008,29(7):77782

Adipocitocinas
Citocina Adiponectin Leptin Resistin Visfatin Retinolbinding protein4 TNFAlfa IL6 Angiotensinogen Plasminogenactivator inhibitor1(PAI1 VisceralFat ++ + ? ++ + + ++ ++ ++
SubcutaneousFat Expressionin Obesity Effecton InsulinSensitivity

+ ++ ? + ++ ++ + + + ? ? =

CurrentPharmaceuticalDesign2007:13;21482168

Adiponectina
Potentantiatherogenicfunctions. Suppressesmonocyteattachmenttovascular Suppressesmonocyte

endothelialcellsbyinhibitingtheexpression endothelialcellsbyinhibitingtheexpressionof adhesionmolecules. Attenuatesgrowthfactorinducedproliferation factorinduced ofvascularsmoothmusclecellsbytheinhibition musclecellsbytheinhibition ofmitogenactivatedproteinkinase. activatedproteinkinase.

CurrentPharmaceuticalDesign2007:13;21482168 CurrentPharmaceuticalDesign2007:13;2148

Adiponectina
Protectsplaquerapturebytheinhibition ofmatrixmetalloproteinasefunction. Isthemost importantadipocytokinewhich preventcardiovasculardiseaseaswellas metabolicdiseasesincludingtype2 diabetes.

CurrentPharmaceuticalDesign2007:13;21482168 CurrentPharmaceuticalDesign2007:13;2148

Fisiopatologa
Pathophysiologicalconditions. Hypoadiponectinemia. Geneticvariationin Adiponectingene Adiponectin Obesity Insulinresistance Type2diabetes Metabolicsyndrome Dyslipidemia Cardiovasculardisease Hypertension Sexhormones(androgen,testosterone) Oxidativestress Carbohydraterichdiet
J.Clin.Invest.2006:116;17841792

Resistenciaalainsulina Resistenciaalainsulina

InformeMedico2008;10(4):195201

ProtenaCreactiva ProtenaCreactiva

NutritionReviews2007:65(II);S152156

Resistenciaalainsulina
Graphof tvaluesof thepartialregression coefficients between waistcircumference, insulinresistance and hyperinsulinemia versuseachfeature ofthemetabolic syndrome,the shadedareaarenot statistically significant.

JNEPHROL2009;22:2938

ABNORMALITIESASSOCIATEDWITHINSULINRESISTANCE ABNORMALITIESASSOCIATEDWITHINSULINRESISTANCE ANDHYPERINSULINEMIA

Abnormalglucosemetabolism

Impairedfastingglucose Impairedglucosetolerance Abnormaluricacidmetabolism Plasmauricacidconcentration Plasmauricacidconcentration Renaluricacidclearance Renaluricacidclearance Dyslipidemia Triglycerides HDLcholesterol LDLparticlediameter Postprandiallipemia
JNEPHROL2009;22:2938

ABNORMALITIESASSOCIATEDWITHINSULINRESISTANCE ABNORMALITIESASSOCIATEDWITHINSULINRESISTANCE ANDHYPERINSULINEMIA

Hemodynamic

Sympatheticnervoussystemactivity Sympatheticnervoussystemactivity Renalsodiumretention Bloodpressure(about50%ofpatientswith Bloodpressure(about50%ofpatientswith hypertension areinsulinresistant) Hemostatic Plasminogenactivatorinhibitor Plasminogenactivatorinhibitor1 Fibrinogen Vasculardysfunction Endothelialdysfunction Microalbuminuria
JNEPHROL2009;22:2938

Ateroesclerosis Ateroesclerosis

JNEPHROL2009;22:2938

Fisiopatologa Fisiopatologa

JNEPHROL2009;22:2938

ClinicalMeasure
Insulinresistance

WHO(1998)
IGT,IFG,T2DM,orloweredinsulin sensitivity plusany2ofthefollowing Men:waisttohipratio >0.90; women:waisttohipratio > 0.85 and/orBMI >= 30 kg/m2 TG >=150 mg/dLand/orHDLC < 35 mg/dLinmenor <39 mg/dL inwomen >=140/90 mmHg IGT,IFG,orT2DM

Bodyweight

Lipid

Bloodpressure Glucose Microalbuminuria Other

EndocrineReviews,December2008,29(7):777822 EndocrineReviews,December2008,29(7):777822

Cualidades:(NCEP:ATPIII) Criteriosmasclnicos. Noserequieredeestudiosdelaboratorio sofisticados(ej.Resistenciaalainsulina). nfasisenlaobesidadvisceral (circunferenciadelacintura) Norequieredelademostracinde resistenciaalainsulina resistenciaalainsulinaperse. IncluyoapacienteconDM2.
GonzlezA,LavalleFJ,RosJJ.Conceptosactualesycriteriosdiagnsticosdel sndromemetablico.Sndromemetablicoyenfermedadcardiovascular.1. Ed.Mxico.Intersistemas2006.pp.7 21

ClinicalMeasure
Insulin resistance

NCEP:ATPIII(2001)
None, but any3of the following5 Features WC>102 WC>102cminmenor > 88 cminwomen cmin TG >= 150mg/dL HDLC < 40mg/dLinmen 40 or <50 mg/dLinwomen >= 130/85mmHg 130/85 >= 110 mg/dL(includes diabetes) diabetes

AACE (2003)
IGTor IFG plus anyofthe followingbasedon clinicaljudgment BMI>= 25 kg/m2 TG >= 150 mg/dLand HDLC<40 mg/dLin menor <50 mg/dLin Women >= 130/85 mmHg IGT orIFG(butnot diabetes) Other featuresof insulin resistance

Body weight

Lipid

Blood pressure Glucose Other

EndocrineReviews,December2008,29(7):777822

Caractersticas:(AACE) Puntualizaronlainterdependenciaderiesgo cardiovascularyenfermedadmetabolica. Focalizaronlaimportanciadeloquellamaron sindromederesistenciaalainsulinacomocausa primariadelosfactoresderiesgometabolico. ExcluyeronalospacienteconDM2. Otrosfactoresderiesgo: syndromedeovariospoliquisticos,diabetes gestacionalprevia,estilodevidasedentario,edad, etnia. HistoriadeDM2enlafamilia,hipertension, enfermedadcardiovascularohiperuricemia.
Circulation.2005;112:218.

ClinicalMeasure
Insulin resistance

AACE AACE(2003)
IGTor IGTorIFG plus anyofthe followingbasedon clinicaljudgment BMI>=25 kg/m2

IDF(2005)
None

Body weight

Lipid

TG >= 150mg/dLand 150 HDLC<40mg/dLin C<40 menor <50mg/dLin <50 Women >= 130/85mmHg 130/85

IncreasedWC(population specific) plus any2ofthe following TG _150mg/dLoronTG Rx HDL C _40mg/dLinmen or50 mg/dL inwomenor on HDLCRx

Blood pressure Glucose Other

IGT orIFG(butnot diabetes) Other featuresof insulin resistance

130 mmHgsystolicor _85mmHgdiastolicoron hypertensionRx 100 mg/dL(includes diabetes)

CurrOpininCardiol2010:25:502512

Cualidades:(IDF) Intentaidentificarpoblacinconriesgode DM2yeventosvasculares. Requieredepresenciadeobesidadcentral conunpuntodecohorteespecificoporetnia. y2factoresmas. Resaltalarelacinentrelaobesidadcentraly enfermedadcardiovascularyotrosfactores. LaobesidadcentralporTACabdominal.

CurrentVascularPharmacology,2006,4,185197

ClinicalMeasure
Body weight

IDF(2005)
IncreasedWC(population IncreasedWC(populationspecific) Plusany2 ofthefollowing TG>= 150 mg/dLoronTGRx mg/dLoronTG

AHA/NHLBI(2005)
3of5constituteSxMet

waistcircumference >=102cminmen >=88cminwomen

Elevatedtriglycerides >= 150 mg/dLOrOndrugtreatment forelevatedtriglycerides ReducedHDLC< 40mg/dL in men < 50mg/dLinwomen Orondrugtreatmentfor reduced HDLC >=130mmHgsystolicblood pressureor>=85mmHg diastolic Orontreatment Elevatedfastingglucose>100 mg/dL Orondrugtreatment

Lipid

HDLC<40mg/dLinmenor<50mg/dL C<40mg/dLinmenor<50mg/dL inwomenoron inwomenoronHDLCRx

Blood pressure

>=130 mmHgsystolicor >= 85 mmHgdiastolicoron hypertensionRx >100 mg/dL(includes diabetes)

Glucose

CurrOpininCardiol2010:25:502512

Clinical Measure

AHA/NHLBI(2005)
3of5constituteSxMet

HarmonizingtheMetabolic Syndrome(2009)
3of5constituteSxMet

Body weight

waistcircumference >=102cminmen >=88cminwomen

Elevatedtriglycerides >=150mg/dL >= OrOndrugtreatmentforelevated triglycerides

Population andcountryspecific definitions

Elevatedtriglycerides >= 150mg/dL OrOndrugtreatmentforelevated triglycerides ReducedHDLC< 40mg/dL inmen < 50mg/dLinwomen Orondrugtreatmentforreduced HDLC >=130mmHgsystolicbloodpressure or>=85mmHgdiastolic Orontreatment Elevatedfastingglucose>100mg/dL Orondrugtreatment Circulation2009;120:16401645

Lipid

ReducedHDLC< 40mg/dL inmen < 50mg/dLinwomen Orondrugtreatmentforreduced HDLC >=130mmHgsystolicbloodpressure or>=85mmHgdiastolic Orontreatment Elevatedfastingglucose>100mg/dL Orondrugtreatment

Blood pressure

Glucose

Population
Caucasian

Organization
WHO

MenWC
>=94cm(increasedrisk)
>=102cm(stillhigherrisk)

WomenWC
>=80cm(increasedrisk)
>=88cm(stillhigherrisk)

United States Canada European

AHA/NHLBI(ATPIII) HealthCanada EuropeanCardiovascular Societies IDF

>=102cm >=102cm >=102cm >=90cm >=85cm >=85cm >=94cm >=94cm >=90cm

>=88cm >=88cm >=88cm >=80cm >=90cm >=80cm >=80cm >=80cm >=80cm

Circulation2009;120:16401645

Asian (including Japanese) Japanese China Middle East,Mediterranean SubSaharanAfrican

JapaneseObesitySociety CooperativeTaskForce IDF

IDF

EthnicCentraland SouthAmerican

IDF

Clinical Measure

ConsensustheMetabolic Syndrome(2009)
3of5constituteSxMet

Report 2011???
3of5constituteSxMet

Body weight

Population andcountry andcountryspecific Population andcountryspecific definitions definitions

Elevatedtriglycerides >= 150mg/dL OrOndrugtreatmentforelevated triglycerides Elevatedtriglycerides >= 150mg/dL OrOndrugtreatmentforelevated triglycerides ReducedHDLC< 40mg/dL inmen < 50mg/dLinwomen Orondrugtreatmentforreduced HDLC ??? mmHgsystolicbloodpressureor ???? mmHgdiastolic Orontreatment Elevatedfastingglucose>100mg/dL OrondrugtreatmentOr

Lipid

ReducedHDLC< 40mg/dL inmen < 50mg/dLinwomen Orondrugtreatmentforreduced HDLC >=130mmHgsystolicbloodpressure or>=85mmHgdiastolic Orontreatment Elevatedfastingglucose>100mg/dL Orondrugtreatment

Blood pressure

Glucose

Hb1AC>=6.5%
DIABETESCARE2010:33;supplS62 S69

1.A1C6.5%.Thetestshouldbeperformedina laboratoryusingamethodthatisNGSP certifiedandstandardizedtotheDCCTassay.*

OR 2.FPG126mg/dl(7.0mmol/l).Fastingisdefinedasnocaloricintakeforatleast8h.* OR 3. 2hplasmaglucose200mg/dl(11.1mmol/l)duringanOGTT.Thetestshouldbe hplasmaglucose200mg/dl(11.1mmol/l)duringanOGTT.Thetestshouldbe performedasdescribedbytheWorldHealthOrganization,usingaglucoseload containing theequivalentof75ganhydrousglucosedissolvedinwater.* OR 4.Inapatientwithclassicsymptomsofhyperglycemiaorhyperglycemiccrisis,a random plasmaglucose200mg/dl(11.1mmol/l).

*Intheabsenceofunequivocalhyperglycemia, criteria13shouldbeconfirmedbyrepeattesting 3shouldbeconfirmedbyrepeattesting

DIABETESCARE2010:33;supplS62 S69

Clinical Measure

ConsensusMetabolicSyndrome(2009) 3of5constituteSxMet

Body weight

Population Population andcountryspecificdefinitions Elevatedtriglycerides >= 150mg/dLOrOndrug treatmentforelevatedtriglycerides

Lipid

ReducedHDLC< 40mg/dL inmen < 50mg/dLinwomen Orondrugtreatmentforreduced HDLC >=130mmHgsystolicbloodpressureor>=85mmHg diastolic Orontreatment Elevatedfastingglucose>100mg/dL Orondrugtreatment CurrOpininCardiol2010:25;502512

Blood pressure Glucose

 Makediagnosisofmetabolicsyndrome. CalculateFraminghamriskscore(age,LDL,

HDL,BP,DM,smoke). A:Aspirin Highrisk aspirindefinitelybeneficial Highintermediaterisk(1020%) aspirin Highintermediaterisk(10 likelytobebeneficial Lowintermediaterisk(6 intermediaterisk(610%) individualizeddecisionmaking,depending individualizeddecision onsexandriskofbleeding.
CurrOpininCardiol2010,25:502512

 B:BPcontrol. AimforBP125135/80mmHg. 135/80mmHg. ACEIs/ARBsfirstlinemayreduceincident

diabetesmellitus. Dihydropyridinecalciumchannelblockers secondline. Betablockersandthiazidesthirdlinemay blockersandthiazidesthirdlinemay haveanadverseeffect.

CurrOpininCardiol2010,25:502512

 C:Cholesterol. Firsttarget:LDL

StatinstoachieveLDLC<100mg/dlinhighrisk, StatinstoachieveLDL <130mg/dlinintermediaterisk(6%10yearrisk) <130mg/dlinintermediate patients Secondtarget:nonHDLStatinintensification, HDLStatinintensification, considerniacinandomega3fattyacidsonce considerniacinandomega statinmaximized. Considerfurtherreductionin LDLwithstatintherapytomitigateriskoflow HDL,considerniacin.
CurrOpininCardiol2010,25:502512

 Thirdtarget: HDLConsiderfibrates,especiallyforthose withcombinedhypertriglyceridemia/low HDL, Fourthtarget: CRPStatintherapyforthosewithCRP=o >2mg/dl.

CurrOpininCardiol2010,25:502512

 D:Diabetesprevention/diet D:Diabetesprevention/diet. Intensivelifestylemodificationisthemost importanttherapyWeightloss,reductioninsalt intake. Mediterraneandiet:increaseomega Mediterraneandiet:increaseomega3fatty acids,fruits,vegetables,fiber,nuts Consider dietarysupplementationwitholyunsaturated fattyacids.
CurrOpininCardiol2010,25:502512

 Metforminissecondlineindelayingthe onsetofdiabetesmellitus. Thiazolidinediones,alpha Thiazolidinediones,alphaglycosidase inhibitors,andincretinmimeticshave shownbenefitinsmallerstudiesandare thereforethirdline.

CurrOpininCardiol2010,25:502512

 E:Exercise Dailyvigorousactivity. Recommenduseofpedometerwithgoal

>10000steps/day.

CurrOpininCardiol2010,25:502512