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METABOLICMETABOLIC
SYNDROMESYNDROME
PRESENTED BYPRESENTED BY--
DR.MAHESH MAWLIYADR.MAHESH MAWLIYA
DEPARTMENT OF MEDICINE
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Clustering ofComponents:Clustering ofComponents:
HypertensionHypertension
HypertriglyceridemiaHypertriglyceridemia
Low HDLLow HDL--cholesterolcholesterol
Obesity (central)Obesity (central)
Impaired Glucose HandlingImpaired Glucose Handling Microalbuninuria (WHO)Microalbuninuria (WHO)
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Other Names Used:Other Names Used:
Syndrome XSyndrome X
CardiometabolicCardiometabolic SyndromeSyndrome
CardiovascularCardiovascular DysmetabolicDysmetabolic SyndromeSyndrome
InsulinInsulin--Resistance SyndromeResistance Syndrome
Metabolic SyndromeMetabolic Syndrome Beer BellySyndromeBeer BellySyndrome
ReavensReavens SyndromeSyndrome
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Criteria fordiagnosis:Criteria fordiagnosis:
World Health OrganizationWorld Health Organization
International Diabetes Federation (IDF)International Diabetes Federation (IDF) --
European Association for the Study ofEuropean Association for the Study ofDiabetes (EASD)Diabetes (EASD)
National Cholesterol Education Project,National Cholesterol Education Project,
Adult Treatment Panel (NCEPAdult Treatment Panel (NCEP--ATP III)ATP III)
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WHO:WHO:
Obesity:Obesity:W/H ratio > 0.9 Men >0.85 WomenW/H ratio > 0.9 Men >0.85 Women
BP:BP: > 140/90 mm of Hg> 140/90 mm of Hg
Glucose:Glucose: presence of DM, IGT, IFG,presence of DM, IGT, IFG,Insulin resistanceInsulin resistance
Triglyceride:Triglyceride: > 150 mg/dl> 150 mg/dl
HDL:HDL:
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IDF:IDF: Ob
esity:Ob
esity:waist circumference >90 cm for Asian men,waist circumference >90 cm for Asian men,
>80 cm for women.>80 cm for women.
BP:BP: >130/85 Or Dxed HT Or Medication.>130/85 Or Dxed HT Or Medication. Triglycerides:Triglycerides:>150mg/dl Or med.>150mg/dl Or med.
HDL:HDL:
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NCEP ATP III:NCEP ATP III:
Obesity:Obesity: >102cm in men>102cm in men
>88cm in women>88cm in women
BP:BP: >130/85mm of Hg>130/85mm of Hg
Triglycerides:Triglycerides: >150mg/dl>150mg/dl
HDL:HDL:
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Linked Metabolic Abnormalities:Linked Metabolic Abnormalities:
Impaired glucose handling/insulinImpaired glucose handling/insulinresistanceresistance
Atherogenic dyslipidemiaAtherogenic dyslipidemia Endothelial dysfunctionEndothelial dysfunction
Prothrombotic stateProthrombotic state
Hemodynamic changesHemodynamic changes Proinflammatory stateProinflammatory state
Excess ovarian testosterone productionExcess ovarian testosterone production
SleepSleep--disordered breathingdisordered breathing
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RISK FACTORSRISK FACTORS
ObesityObesity
S
edentary life styleS
edentary life styleAgingAging
DMDM
Coronary Heart DiseaseCoronary Heart Disease
LipodystrophyLipodystrophy
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Obesity:Obesity:
Central obesityCentral obesityis theis the
key feature ofkey feature ofmetabolic syndrome.metabolic syndrome.
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SedentarylifestyleSedentarylifestyle
Individuals who watched TV orIndividuals who watched TV orvideos or used their computervideos or used their computer
> 4 hr/day have 2 fold> 4 hr/day have 2 foldincreased risk of Metabolicincreased risk of Metabolic
syndrome.syndrome.
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Diabetes Mellitus:Diabetes Mellitus:
About 75% of patients withAbout 75% of patients with
DM II or IGT have theDM II or IGT have theMetabolic syndrome.Metabolic syndrome.
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CHDCHD
50% patients of coronary50% patients of coronary
heart disease have metabolicheart disease have metabolic
syndrome.syndrome.
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ETIOLOGYOFETIOLOGYOFMETABOLIC SYNDROMEMETABOLIC SYNDROME
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InsulinresistanceInsulinresistance
Increased circulating free fatty acidsIncreased circulating free fatty acidslead to insulin resistance by acting onlead to insulin resistance by acting on
liver & muscles.liver & muscles.Defect in insulin action lead toDefect in insulin action lead to
postprandial hyperinsulinemia >postprandial hyperinsulinemia >fasting hyperinsulinemia >fasting hyperinsulinemia >hyperglycemia.hyperglycemia.
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HowinsulinresistanceleadstoHowinsulinresistanceleadsto
coronarydiseasecoronarydisease
Genetic inslin resistance enviornmentalGenetic inslin resistance enviornmental
influenceinfluence influenceinfluenceHyperinsulinemiaHyperinsulinemia
Glucose increased increased decreased increasedGlucose increased increased decreased increased
intolerance TG Uric Acid HDL B.P.intolerance TG Uric Acid HDL B.P.
Coronary artery diseaseCoronary artery disease
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Oxidativestresshypothesis.Oxidativestresshypothesis.
In elderly persons. defectiveIn elderly persons. defectivemitochondrial oxidativemitochondrial oxidative
phosphorydation leads tophosphorydation leads toaccumulation of TGs & relatedaccumulation of TGs & related
lipids in muscle > insulinlipids in muscle > insulinresistance.resistance.
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GlucoseintoleranceGlucoseintolerance
Defect in insulin action lead toDefect in insulin action lead toimpaired suppression of glucoseimpaired suppression of glucose
production by liver & reducedproduction by liver & reduceduptake by muscle or adipose tissue.uptake by muscle or adipose tissue.
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HypertensionHypertension
Vasodilatory effect of insulin lostVasodilatory effect of insulin lostin metabolic syndrome.in metabolic syndrome.
Na reabsorption in kidney &Na reabsorption in kidney &increased sympathetic activity leadincreased sympathetic activity lead
to hypertension.to hypertension.
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ProinflammatoryProinflammatory cytokinescytokines
IL 1, IL 6, IL 18, resistin, TNF alfa & CRPIL 1, IL 6, IL 18, resistin, TNF alfa & CRPproduced by adipose tissue derivedproduced by adipose tissue derived
macrophages & associated with M S.macrophages & associated with M S.ADIPONECTIN an anti inflammatoryADIPONECTIN an anti inflammatory
cytokine produced exclusively by adipocytes.cytokine produced exclusively by adipocytes.increased glucose uptake & fatty acidincreased glucose uptake & fatty acidoxydation, reduced in M S.oxydation, reduced in M S.
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Clinical featuresClinical features
Cardiovascular diseaseCardiovascular disease
1.5 to 3 fold increased risk1.5 to 3 fold increased risk
DM Type IIDM Type II
3 to 4 fold increased risk3 to 4 fold increased risk
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Other asso.conditionsOther asso.conditions
Increased apo B & C III,Increased apo B & C III,
uric acid,uric acid,
prothrombotic factor (fibrinogen, PAI 1),prothrombotic factor (fibrinogen, PAI 1), serum viscosity,serum viscosity,
homocysteine,homocysteine,
WBC count,WBC count, proinflammatory cytokines,proinflammatory cytokines,
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microalbuminuria,microalbuminuria,
CRP,CRP,
NAFLD,NAFLD,
NASH,NASH,
PCOS,PCOS,
OSA,OSA,
Ca(liver, breast, prostate)Ca(liver, breast, prostate)
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Diagnosis:Diagnosis:
Physical ExaminationPhysical Examination
BPBP
Waist circumferenceWaist circumferenceW/H ratioW/H ratio
AtheromasAtheromas
Skin tagsSkin tagsAcanthosisAcanthosis nigricansnigricans
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Lab.evaluationLab.evaluation
Fasting glucose levelFasting glucose level
Lipid profileLipid profile
CRP HSCRP HSTSHTSH
Hb A1cHb A1c
LFTLFT HomocysteineHomocysteine
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Lab. EvaluationcontLab. Evaluationcont
Uric acidUric acid
CreatinineCreatinine
FibrinogenFibrinogen Urinary microalbuminUrinary microalbumin
Sleep study of OSASleep study of OSA
TestosteroneTestosterone
FSHFSH
LHLH
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Why TreatWhy Treat
Metab
olicsyndrome?Metab
olicsyndrome?
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BecauseItHoldsthe SameBecauseItHoldsthe Same
Coronary Riskas Diab
etes!!Coronary Riskas Diab
etes!!
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One More ReasonOne More Reason50% of patients with Impaired50% of patients with Impaired
Fasting Glucose will go on to becomeFasting Glucose will go on to become
diabetic within 10 yearsdiabetic within 10 years
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Multiple RiskFactorMultiple RiskFactor
ManagementManagementObesityObesity
Glucose IntoleranceGlucose Intolerance
Insulin ResistanceInsulin ResistanceLipid DisordersLipid Disorders
HypertensionHypertensionGoals:Goals: Minimize Risk of Type 2 DiabetesMinimize Risk of Type 2 Diabetes
and Cardiovascular Disease.and Cardiovascular Disease.
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DiabetesControlDiabetesControl -- HowHow
I
mportant?I
mportant? For every 1% rise in Hgb A1c there is anFor every 1% rise in Hgb A1c there is an
18% rise in risk of cardiovascular events & a18% rise in risk of cardiovascular events & a
28% increase in peripheral arterial disease28% increase in peripheral arterial disease Evidence is accumulating to show that tightEvidence is accumulating to show that tight
blood sugar control in both Type 1 and Typeblood sugar control in both Type 1 and Type2 diabetes reduces risk of CVD2 diabetes reduces risk of CVD
GoalsGoals:: BSBS -- premeal 90premeal 90--130, postmeal130, postmeal
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BP ControlBP Control -- HowImportant?HowImportant?
MRFIT and Framingham Heart Studies:MRFIT and Framingham Heart Studies:
Conclusively proved the increased risk ofConclusively proved the increased risk ofCVD with longCVD with long--term sustained hypertensionterm sustained hypertension
Demonstrated a 10 year risk of cardiovascularDemonstrated a 10 year risk of cardiovasculardisease in treated patients vs nondisease in treated patients vs non--treatedtreated
patients to be 0.40.patients to be 0.40. 40% reduction in stroke with control of40% reduction in stroke with control of
HTNHTN
Goal:Goal:
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LipidControlLipidControl -- HowImportant?HowImportant?
Multiple major studies show 24Multiple major studies show 24 -- 37% reductions in37% reductions incardiovascular disease risk with use of statins andcardiovascular disease risk with use of statins andfibrates in the control of hyperlipidemia.fibrates in the control of hyperlipidemia.
Goals:Goals: LDL
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LifeLife--Style Modification:IsitStyle Modification:Isit
Important?Important?
ExerciseExercise
Improves CV fitness, weight control, sensitivityImproves CV fitness, weight control, sensitivityto insulin,to insulin, reduces incidence of diabetesreduces incidence of diabetes
WeightlossWeightloss
Improves lipids, insulin sensitivity, BP levels,Improves lipids, insulin sensitivity, BP levels,reduces incidence of diabetesreduces incidence of diabetes
Goals:Goals: Brisk walkingBrisk walking -- 30 min./day30 min./day
10% reduction in body wt.10% reduction in body wt.
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SmokingCessation/Avoidance:SmokingCessation/Avoidance:
A risk factor for development in children andA risk factor for development in children andadultsadults
Both passive and active exposure harmfulBoth passive and active exposure harmful
AA majormajor risk factorrisk factor for:for:
insulin resistance and metabolic syndromeinsulin resistance and metabolic syndrome
macrovascular disease (PVD, MI, Stroke)macrovascular disease (PVD, MI, Stroke)
microvascular complications of diabetesmicrovascular complications of diabetes
pulmonary disease.pulmonary disease.
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Antihypertensive Medications:Antihypertensive Medications:
AngiotensinAngiotensin--converting Enzymeconverting EnzymeInhibitors (ACEI)Inhibitors (ACEI)
AngiotensinAngiotensin II Receptor (ARB)II Receptor (ARB)BlockersBlockers
Combination withCombination with ThiazidesThiazides, Calcium, Calcium
Channel Blockers,Channel Blockers, CardioselectiveCardioselective BetaBetaBlockersBlockers
Target BPTarget BP:
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Insulin Resistance/Diabetes:Insulin Resistance/Diabetes:
Insulin Sensitizers:Insulin Sensitizers:
BiguanidesBiguanides -- metforminmetformin
PPAR , & agonistsPPAR , & agonists -- GlitazonesGlitazones,,GlitazarsGlitazars
Can be used in combinationCan be used in combination
InsulinInsulin SecretagoguesSecretagogues::
SulfonylureasSulfonylureas -- glipizideglipizide,, glyburideglyburide,,
glimeparideglimeparide,, glibenclamideglibenclamide
MeglitinidesMeglitinides -- repaglaniderepaglanide,, netiglamidenetiglamide
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InsulinInsulin
Insulin Analogues:Insulin Analogues: LysLys--pro/Aspart/glulysine used with mealspro/Aspart/glulysine used with meals
Glargine as basal insulinGlargine as basal insulin
Continuous Subcutaneous Insulin InfusionContinuous Subcutaneous Insulin Infusion(CSII)(CSII)
NPH/Regular, NPH/logsNPH/Regular, NPH/logs -- Mixed or in fixedMixed or in fixed
combinations (70/30, 75/25, 50/50)combinations (70/30, 75/25, 50/50) Insulin combined with oral agentsInsulin combined with oral agents
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New Pharmacologic Agents:New Pharmacologic Agents:
Incretin Mimetics:Incretin Mimetics:
GLPGLP--1 agonist1 agonist -- exenatideexenatide
Dual PPAR Dual Agonists:Dual PPAR Dual Agonists:
GlitazarsGlitazars
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Lipidloweringdrugs:Lipidloweringdrugs:
StatinsStatins
FibratesFibrates
Nicotinic acidNicotinic acid Bile acid sequestrantsBile acid sequestrants
Cholesterol absorption inhibitorCholesterol absorption inhibitor
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LDL
HDLTRIGLYCERIDES
Small Dense LDL No effect
Effect of insulin
resistanceNone
May
increase
May
Decrease
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Screening/PublicHealthScreening/PublicHealth
ApproachApproach Screening for at risk individuals:Screening for at risk individuals:
Blood Sugar/Hgb A1cBlood Sugar/Hgb A1c
LipidsLipids
Blood pressureBlood pressure
Tobacco useTobacco use
Body habitusBody habitus
Family historyFamily history
Public EducationPublic Education
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Thank youThank you