Met Syndrome

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Cardiometabolic SyndromeNabil Sulaiman

HOD Family and Community Medicine, Sharjah

University and University of Melbourne

&

Dr Dhafir A. MahmoodConsultant EndocrinologistAl- Qassimi & Al-Kuwait Hospital

Sharjah


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Cardiometabolic Syndrome II

Aims Abdominal obesity prevalence

Targeting Cardiometabolic Risk factors

Multiple Risk Factor management A Critical Look at the Metabolic Syndrome


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Clustering of Components:

Hypertension: BP. > 140/90

Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L )

HDL- C < 35 mg/ dL (0.9 mmol/L)

Obesity (central): BMI > 30 kg/M2

Waist girth > 94 cm (37 inch)

Waist/Hip ratio > 0.9

Impaired Glucose Handling: IR , IGT or DM

FPG > 110 mg/dL (6.1mmol/L)2hr.PG >200 mg/dL(11.1mmol/L)

Microalbuninuria (WHO)


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Global cardiometabolic risk*

Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition


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The new IDF definition focusses on abdominal obesity

rather than insulin resistance

International Diabetes Federation(IDF) Consensus Definition 2005


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Why a New Definition of theMeS: IDF Objectives

Needs:

To identify individuals at high risk of developingcardiovascular disease (and diabetes)

To be useful for clinicians

To be useful for international comparisons


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Fat Topography In Type 2

Diabetic Subjects

Intramuscular

Intrahepatic

Subcutaneous

Intra-abdominal

FFA*TNF-alpha*

Leptin*IL-6 (CRP)*Tissue Factor*PAI-1*

Angiotensinogen*


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Abdominal obesity and increased risk ofcardiovascular events

Dagenais GR et al, 2005

Adjustedrelativer

isk

1 1 1

1.17 1.16 1.14

1.29 1.27

1.35

0.8

1

1.2

1.4

CVD death MI All-cause deaths

Tertile 1

Tertile 2

Tertile 3

Men Women

103

98

Waistcircumference (cm):

The HOPE study

Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C;CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index;

DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol


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Abdominal obesity increases the risk ofdeveloping type 2 diabetes

96.3

24

20

16

12

8

4

0

Relativerisk

Waist circumference (cm)

Carey VJ et al, 1997


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Abdominal obesity is linked to anincreased risk of coronary heart disease

Waist circumference has been shown to be independentlyassociated with increased age-adjusted risk of CHD, even after

adjusting for BMI and other cardiovascular risk factors

0.0

0.5

1.0

1.5

2.0

2.5

3.0


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Diabetes in the new millenniumInterdisciplinary problem

Diabetes


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OBESITY


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DIAB

ESITY


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Targeting

Cardiometabolic Risk


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Central obesity: a driving force forcardiovascular disease & diabetes

Balzac by RodinFront

Back


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Insulin Resistance: AssociatedConditions


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Linked Metabolic Abnormalities:

Impaired glucose handling/ insulin

resistance Atherogenic dyslipidemia

Endothelial dysfunction

Prothrombotic state

Hemodynamic changes

Proinflammatory state Excess ovarian testosterone production

Sleep-disordered breathing


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Resulting Clinical Conditions:

Type 2 diabetes Essential hypertension

Polycystic ovary syndrome (PCOS)

Nonalcoholic fatty liver disease

Sleep apnea

Cardiovascular Disease (MI, PVD, Stroke)

Cancer (Breast, Prostate, Colorectal,Liver)


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Multiple Risk Factor Management

Obesity

Glucose Intolerance

Insulin Resistance

Lipid Disorders

Hypertension

Goals:Minimize Risk of Type 2Diabetes and Cardiovascular Disease


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Glucose Abnormalities:

IDF: FPG >100 mg/dL (5.6 mmol. L) or previously

diagnosed type 2 diabetes

(ADA: FBS >100 mg/dL [ 5.6 mmol/L ])


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Hypertension:

IDF:

BP >130/85 or on Rx for previouslydiagnosed hypertension


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Dyslipidemia:

IDF: Triglycerides - >150mg/dL (1.7 mmol /L)

HDL -


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Public Health Approach


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Screening/Public Health Approach

Public Education

Screening for at risk individuals:

Blood Sugar/ HbA1c

Lipids

Blood pressure

Tobacco use

Body habitus

Family history


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Life-Style Modification: Is it Important?

Exercise

Improves CV fitness, weight control, sensitivityto insulin, reduces incidence of diabetes

Weight loss Improves lipids, insulin sensitivity, BP levels,

reduces incidence of diabetes

Goals:

Brisk walking - 30 min./day

10% reduction in body wt.


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Smoking Cessation / Avoidance:

A risk factor for development in children and adults

Both passive and active exposure harmful

A majorrisk factorfor: insulin resistance and metabolic syndrome

macrovascular disease (PVD, MI, Stroke)

microvascular complications of diabetes

pulmonary disease, etc.


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Diabetes Control - How Important?

Goals:

FBS - premeal


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Lifestyle modification

Diet Exercise Weight loss

Smokingcessation

If a 1% reduction in HbA1c

is achieved, you couldexpect a reduction in riskof:

21% for any diabetes-related endpoint

37% for microvascularcomplications

14% for myocardialinfarction

However, compliance is poor and most patients will requireoral pharmacotherapy within a few years of diagnosis

Stratton IM et al. BMJ2000; 321: 405412.


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Overcome Insulin Resistance/ Diabetes:

Insulin Sensitizers: Biguanides metformin

Glitazones, Gltazars

Can be used in combination

Insulin Secretagogues:

Sulfonylurea - glipizide, glyburide,glimeparide, glibenclamide

Meglitinides - repaglanide, netiglamide


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BP Control - How Important?

Goal:BP.


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Lipid Control - How Important?

Goals: HDL >40 mg% (>1.1 mmol /l)

LDL


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Substantial residual cardiovascularrisk in statin-treated patients

PlaceboStatin

Year of follow-up

%p

atients

0 1 2 3 4 5 6

10

20

30

0

Risk reduction=24%(p


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Medications:

Hypertension:

ACE inhibitors, ARBs

Others - thiazides, calcium channel

blockers, beta blockers, alpha blockers Central acting Alfa agonist : Moxolidin

Dylipidemia:

Statins, Fibrates, Niacin Platelet inhibitors:

ASA, clopidogrel


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Individual metabolic abnormalities among Qatari


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Individual metabolic abnormalities among Qataripopulation according to gender (Musallam et al 08)

Men (n = 405) Women (n=412)

Variable n(%) n(%) p-Value

ATP III

Abdominal obesity 227(56.0) 308(74.8)


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Individual metabolic abnormalities among Qataripopulation according to gender

Men (n = 405) Women (n=412)Variable n(%) n(%) p-Value

None 88(21.7) 74(18.0)

One 103(25.4) 100(24.3) 0.033

Two 125(30.9) 111(26.9)

Three or more 89(22.0) 127(30.8)

No of components of ATP III


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Prevalence of MeS in different Countries

Prevalence(%)

SampleYearCountry

235422003Arab Americans

2114192001Oman

3611212002Jordan

20.822502004Saudi Arabia

17*1998Palestine

27.68172007Qatar

33.4*16372004Turkey

33.710368?Iran

* Crude rates Mussallam et al. Int J Food Safety and PH 2008


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A Critical Look at the Metabolic Syndrome

Is it a Syndrome?* too much clinically important information

is missing to warrant its designations as asyndrome.

Unclear pathogenesis, Insulin resistance isnot a consistent finding in some definitions.

CVD risks has not shown to be greater thanthe sum of its individual components.

*ADA


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Research

Until much needed research is

completed, clinicians should evaluate andtreat all CVD risk factors without regard to

whether a patient meets the criteria for

diagnosis of the metabolicsyndrome.


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Lifestyle

The advice remains to treat individual risk

factors when present & to prescribetherapeutic lifestyle changes & weight

management for obese patients with

multiple risk factors.


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Determinants and dynamics of the CVD


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Determinants and dynamics of the CVDEpidemic in the developing Countries

Data from South Asian Immigrant studies

Excess, early, and extensive CHD in persons ofSouth Asian origin

The excess mortality has not been fully explainedby the major conventional risk factors.

Diabetes mellitus and impaired glucose tolerancehighly prevalent. (Reddy KS, circ 1998).

Central obesity, triglycerides, HDL with orwithout glucose intolerance, characterize a

phenotype. genetic factors predispose to lipoprotein(a)

levels, the central obesity/glucoseintolerance/dyslipidemia complex collectively

labeled as the metabolic syndrome

Determinants and dynamics of the CVD


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Determinants and dynamics of the CVDepidemic in the developing countries

Other Possible factors Relationship between early life characteristics and

susceptibility to NCD in adult hood ( Barkershypothesis) (Baker DJP,BMJ,1993)

Low birth weight associated with increased CVD Poor infant growth and CVD relation

Geneticenvironment interactions(Enas EA, Clin. Cardiol. 1995; 18: 1315)

- Amplification of expression of risk to someenvironmental changes esp. South Asian population)

- Thrifty gene (e.g. in South Asians)

CVD epidemic in developing &


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CVD epidemic in developing &developed countries. Are they same?

Urban populations have higher levels of CVD risk

factors related to diet and physical activity(overweight, hypertension, dyslipidaemia and diabetes)

Tobacco consumption is more widely prevalent in ruralpopulation

The social gradient will reverse as the epidemicsmature.

The poor will become progressively vulnerable to theravages of these diseases and will have little access

to the expensive and technology-curative care. The scarce societal resources to the treatment of

these disorders dangerously depletes the resourcesavailable for the unfinished agenda of infectious andnutritional disorders that almost exclusively afflictthe oor


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Burden of CVD in Pakistan

Coronary heart disease

Mortality statistics

Specific mortality data ideal for makingcomparisons with other countries are notavailable

Inadequate and inappropriate death certification,and multiple concurrent causes of death

C l b i d i i f f


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Central obesity: a driving force forcardiovascular disease & diabetes

Balzac by RodinFront

Back


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Why people physically inactive?

Lack of awareness regarding the of physicalactivity for health fitness and prevention ofdiseases

Social values and traditions regardingphysical exercise (women, restriction).

Non-availability public places suitable forphysical activity (walking and cycling path,gymnasium).

Modernization of life that reduce physicalactivity (sedentary life, TV, Computers, tel,cars).


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Prevalence of the Metabolic Syndrome


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Prevalence of the Metabolic SyndromeAmong US Adults NHANES 1988-1994

Prev

alence(%)

0

5

1015

20

25

30

3540

45

20-29 30-39 40-49 50-59 60-69 > 70

MenWomen

Age (years)Ford E et al. JAMA. 2002(287):356.

1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES,

Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+)

NCEP : 33.7% in men and 35.4% in women

IDF: 39.9% in men and 38.1% in women


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Prevention of CVD


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Prevention of CVD

There is an urgent need to establishappropriate research studies, increaseawareness of the CVD burden, and developpreventive strategies.

Prevention and treatment strategies that havebeen proven to be effective in developedcountries should be adapted for developingcountries.

Prevention is the best option as an approachto reduce CVD burden.

Do we know enough to prevent this CVD

Epidemic in the first place.


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The new IDF definition focusses on

abdominal obesity rather than insulinresistance

International Diabetes Federation(IDF) Consensus Definition 2005

International Diabetes Federation (IDF)


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Consensus Definition 2005Central Obesity

Waist circumference ethnicity specific*

for Europids: Male > 94 cm

Female > 80 cm

plus any two of the following:

Raised triglycerides > 150 mg/dL (1.7 mmol/L)

or specific treatment for this lipid abnormality

Reduced HDL cholesterol < 40 mg/dL (1.03 mmol/L) in males

< 50 mg/dL (1.29 mmol/L) in females

or specific treatment for this lipid abnormality

Raised blood pressure Systolic : > 130 mmHg or

Diastolic: > 85 mmHg or

Treatment of previously diagnosed hypertensionRaised fasting plasmaglucose

Fasting plasma glucose > 100 mg/dL (5.6 mmol/L) or

Previously diagnosed type 2 diabetes

If above 5.6 mmol/L or 100 mg/dL, OGTT is stronglyrecommended but is not necessary to define presence of thesyndrome.

Treatment of Metabolic Syndrome: 2005


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Treatment of Metabolic Syndrome: 2005

AspirinDiet,

Exercise,

Lifestylechange

Stopsmoking

CB1 ReceptorBlocker

Oral hypoglycaemics

Antihypertensives

Statins &Fibrates

Insulin

ACEI &/or A2 receptorblockers

R d ti f t t t


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Primary management for the Metabolic Syndrome

is healthy lifestyle promotion. This includes:

moderate calorie restriction (to achieve a 5-10%

loss of body weight in the first year)

moderate increases in physical activity

change dietary composition to reduce saturatedfat and total intake, increase fibre and, ifappropriate, reduce salt intake.

Recommendations for treatment

Management of the Metabolic Syndrome


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Appropriate & aggressive therapy is essential

for reducing patient risk of cardiovasculardisease

Lifestyle measures should be the first action

Pharmacotherapy should have beneficial effectson Glucose intolerance/diabetes

Obesity

Hypertension Dyslipidaemia

Ideally, treatment should address all of thecomponents of the syndrome and not the

individual components

Management of the Metabolic Syndrome

Summary: new IDF definition for the


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yMetabolic Syndrome

clinicalbothThe new IDF definition addresses

and research needs:

provides a simple entry point for primary carephysicians to diagnose the Metabolic Syndrome

providing an accessible, diagnostic toolsuitable for worldwide use, taking into account

ethnic differences

establishing a comprehensive platinum

standard list of additional criteria that should

be included in epidemiological studies and

other research into the Metabolic Syndrome


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Met Syndrome

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