Linked Metabolic AbnormalitiesLinked Metabolic Abnormalities::

• Impaired glucose handling/ insulin resistance

• Atherogenic dyslipidemia

• Endothelial dysfunction

• Prothrombotic state

• Hemodynamic changes

• Proinflammatory state

• Excess ovarian testosterone production

• Sleep-disordered breathing

Resulting Clinical ConditionsResulting 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)

Multiple Risk Factor ManagementMultiple Risk Factor Management

• Obesity

• Glucose Intolerance

• Insulin Resistance

• Lipid Disorders

• Hypertension

• Goals: Goals: Minimize Risk of Type 2 Minimize Risk of Type 2 Diabetes and Cardiovascular DiseaseDiabetes and Cardiovascular Disease

Glucose AbnormalitiesGlucose Abnormalities::

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

diagnosed type 2 diabetes

• WHO:WHO:– Presence of diabetes, IGT, IFG, insulin resistance

• ATP III:ATP III:– FBS >110 mg/dL, <126 mg/dL (6.1-7.1 mmol/L )

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

HypertensionHypertension::

• IDF:IDF:– BP >130/85 or on Rx for previously

diagnosed hypertensionhypertension

• WHO:WHO:– BP >140/90

• NCEP ATP III:NCEP ATP III:– BP >130/80

DyslipidemiaDyslipidemia::

• IDF:IDF:– Triglycerides - >150mg/dL (1.7 mmol /L)– HDL - <40 mg/dL (men), <50 mg/dL

(women)

• WHO:WHO:– Triglycerides - >150 mg/dL (1.7 mmol/L)– HDL - <35 mg/dL (men), >39 mg/dL)

women

• ATP III:ATP III:– Same as IDF

Screening/Public Health ApproachScreening/Public Health Approach

• Public Education

• Screening for at risk individuals:– Blood Sugar/ HbA1c– Lipids– Blood pressure– Tobacco use– Body habitus– Family history

Life-Style Modification: Is it Important?Life-Style Modification: Is it Important?

• Exercise– Improves CV fitness, weight control, sensitivity

to insulin, reduces incidence of diabetes

• Weight loss– Improves lipids, insulin sensitivity, BP levels,

reduces incidence of diabetes

• Goals: Goals: Brisk walking - 30 min./dayBrisk walking - 30 min./day 10% reduction in body wt.10% reduction in body wt.

Smoking Cessation / AvoidanceSmoking Cessation / Avoidance::

• A risk factor for development in children and adults

• Both passive and active exposure harmful

• A major risk factor for:– insulin resistance and metabolic syndrome– macrovascular disease (PVD, MI, Stroke)– microvascular complications of diabetes– pulmonary disease, etc.

Diabetes Control - How ImportantDiabetes Control - How Important??

• For every 1% rise in Hb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease

• Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD

• GoalsGoals:

• FBS - premeal <110, FBS - premeal <110,

• postmealpostmeal <180. <180.

• HbA1c <7%HbA1c <7%

Overcome Insulin Resistance/ DiabetesOvercome Insulin Resistance/ Diabetes::

• Insulin Sensitizers:– Biguanides - metformin– PPAR α, γ & δ agonists – Glitazones, Gltazars Rosiglitazon, Pioglitazon– Can be used in combination

• Insulin Secretagogues:– Sulfonylurea - glipizide, glyburide,

glimeparide, glibenclamide– Meglitinides - repaglanide, netiglamide

BP Control - How ImportantBP Control - How Important??

• MRFIT and Framingham Heart Studies: – Conclusively proved the increased risk of

CVD with long-term sustained hypertension– Demonstrated a 10 year risk of cardiovascular

disease in treated patients vs non-treated patients to be 0.40.

– 40% reduction in stroke with control of HTN

• Precedes literature on Metabolic Syndrome

• Goal: BP.BP.<130/80<130/80

Lipid Control - How ImportantLipid Control - How Important??

• Multiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.

• Goals:Goals: LDL <100 mg/dL (<3.0 mmol /l)LDL <100 mg/dL (<3.0 mmol /l)

(high risk <70 mg/dL- <2.6 mmol/L)(high risk <70 mg/dL- <2.6 mmol/L)

TG <150 mg% (<1.7 mmol /l)TG <150 mg% (<1.7 mmol /l)

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

MedicationsMedications::

• 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

A Critical Look at the Metabolic SyndromeA Critical Look at the Metabolic Syndrome

Is it a Syndrome?*Is it a Syndrome?*• “…too much clinically important information

is missing to warrant its designations as a syndrome.”

• Unclear pathogenesis, Insulin resistance may not underlie all factors, & is not a consistent finding in some definitions.

• CVD risks associated with metabolic syndrome has not shown to be greater than the sum of it’s individual components.

*ADA & EASD

A Critical Look at the Metabolic SyndromeA Critical Look at the Metabolic Syndrome

• “Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the ‘metabolic syndrome’.”

• The advice remains to treat individual risk factors when present & to prescribe therapeutic lifestyle changes & weight management for obese patients with multiple risk factors.

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

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

Variable n(%) n(%) p-ValueATP III

Abdominal obesity 227(56.0) 308(74.8) <0.001

Hypertension 143(35.3) 156(37.9) 0.448

Diabetes 77(19.0) 107(26.0) 0.017

Hypertriglyceridemia 113(27.9) 83(20.1) 0.009

Low HDL 95(23.5) 121(29.4) 0.055

Individual metabolic abnormalities among Qatari population 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

Multivariate logistic regression analysis of factors associated with Metabolic Syndrome according to (ATP III criteria)

Odds ratio 95% CI p-Value

Age 1.07 1.05–1.09 <0.001

Female gender 1.86 1.30–2.67 0.001

Body Mass Index 1.05 1.02–1.07 <0.001

Fam his of DM 1.66 1.12–2.44 0.011

Smoking 3.27 1.63–6.55 0.001

Prevalence of MeS in different Countries

CountryYear SamplePrevalence (%)

Arab Americans200354223

Oman2001141921

Jordan2002112136

Saudi Arabia2004225020.8

Palestine199817*

Qatar200781727.6

Turkey2004163733.4*

Iran?1036833.7

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

Prevalence of MeS in different Countries

CountryYear SamplePrevalence (%)

USA2005200234*

Greece2005141921

South Australia2005406015.3

S. Korea200140,6986.8

China2000277610.2*

Turkey2004163733.4*

Chennai India200347541*

Qatar200181727.6

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