revised maheshs presentation

8/6/2019 Revised Maheshs Presentation

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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

revised maheshs presentation

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