 Eskil Kylin 1923 – HT,  Glucose,  UA

 Reaven 1988 – named Syndrome X (IR)

 WHO definition-1998 – Metabolic syndrome

 NCEP-ATP III – 2001 – MS – strong CV Risk

 First World Congress on IRS – Nov 2003

 Second World Congress on IRS – 2004

 2005 Quarrel about the word “syndrome”

 New IDF definition 2006 - consensus

 Metabolic Syndrome (MS)

 Insulin Resistance Syndrome (IRS)

 Syndrome X (Metabolic), Deadly Quartet

 Dysmetabolic Syndrome, Beer belly syndrome

 Cardiometabolic Syndrome

 Pleuri Metabolic Syndrome

 ICD Code # 277.7

Clustering of CV Risk Factors

Central
Obesity

Insulin
Resistance
 Insulin Resistance

Obesity Metabolic Syndrome Diabetes

2x 4x

Cardio Vascular Disease (CVD)

Reilly MP et al –
Circulation 2003; 108: 1546-1551
 Insulin
Resistance

Inadequate Hyper
Insulin prod Insulinemia

Metabolic
Type 2 DM CAD
Syndrome

HT, Stroke,
CKD
PCOS, NASH
ACE Position Statement on IRS
Endocr Pract. 2003;9(3)
Etiology – not fully elucidated
 Insulin Resistance

 Acquired causes

 Overweight and central obesity

 Physical inactivity, aging, ethnicity

 High CHO diets (>60%)

 Proinflammatory state, hormones

 Poly Genic causes

 IR,  Insulin

IGT, IFG Dyslipidemia

ED, Vessel Increased Hypertension

CV Risk

Pro Thrombotic Visceral obesity

Pro Inflammatory
 Insulin resistance – Hyperinsulinemia

 Abd. Obesity ( WC,  WC / ht ratio),  BMI

 Hyperglycemia – IFG, IGT, T2DM

 Hypertension, Endothelial Dysfunction (ED)

 Dyslipidemia ( TG,  sLDL,  HDL)

 Pro-inflammatory state ( CRP, TNF-, IL-6)

 Pro-coagulant state ( PAI-1,  Fibrinogen)

 Premature atherosclerosis, CAD

 Central
Obesity  TG

 HDL

Hyper-
tension
 FPG
 Subcutaneous fat

Abdominal muscle
layer
Intra-abdominal fat

Is this correct?
M. Davidson, MD.
Previous Criteria Proposed for Clinical Diagnosis of
Metabolic Syndrome
Clinical WHO EGIR ATP III AACE IDF
Measure (1998) (1999) (2001) (2003) (2005)
IGT,IFG,T2DM or Plasma Insulin None, But any 3 of IGT or IFG plus any None
Insulin
Lower insulin sensitivity > 75th percentile the following 5 of following based on
Resistance Plus any 2 of the following Plus any 2 of the Features clinical judgement
following
Men : WHR > 0.90 WC >94 cm in men WC > 102 cm in men BMI > 25 kg/m2 Increase WC
Body
Women : WHR > 0.85 Or Or (population specific)
Weight And/or BMI > 30 kg/m2 >80 cm in women > 88 cm in women Plus any 2 of the
following
TG> 150 mg/.dl or TG >150 mg/dl & TG> 150 mg/.dl or TG> 150 mg/.dl or TG> 150 mg/.dl or
Lipid or
HDL-C<35 mg/dl in men HDL-C<40 mg/dl in men HDL-C<40 mg/dl in HDL-C<40 mg/dl in men
Or < 39 mg/dl in women HDL-C < 39 mg/dl Or < 50 mg/dl in women men Or < 50 mg/dl in women
In men or women Or < 50 mg/dl in
women
> 140/90 mmHg > 140/90 mmHg > 130/85 mmHg 130/85 mmHg > 130 mmHg systolic or
Blood
or non hypertension > 85 mmHg diastolic or
Pressure Non hypertention Rx
IGT, IFG or T2DM IGT or IFG > 110 mg/dl IGT or IFG > 100 mg/dl
Glucose
(but not diabetes) (Include diabetes) (but not diabetes) (include diabetes)
FPG >110 mg/dl (2001)
Microalbuminuria FPG > 100 mg/dl (2004) Other features of
Other
Insulin resistance
(PCOS,T2DM etc)

(Grundy et al, 2005)

Waist Circum  90 (M), 80 (F)

Triglycerides >150 mg

HDL <40 (M) < 50 (F)

2 of 5
Dysglycemia FPG >100 or DM

Hypertension >130 or 85

Rx. for any of the above conditions

Features
Hyperglycemia
Obesity, ↑ WC, ACN
↑ TG, ↓ HDL, ↑ sLDL
Cluster of metabolic factors
Hypertension (>130/80)
Recent weight change
Fasting C peptide / Insulin
Treatment
Insulin Resistance
↑ PPBG, Usually FBG is N
BMI > 23, WC > 90, ACN+
Dyslipidemia Present
Metabolic Syndrome
Usually is a feature
Increase
Increased
Exercise, Sensitizers
 Can we measure insulin resistance ? Yes !

 It will be of use to confirm IR

 Fasting C-Peptide levels, FBG

 CISI – Composite Insulin Sensitivity Index

 QUICKI – Quantitative Insulin Sensitivity Index

 HOMA IR – Homeostasis Model Assessment

 HOMA calculator is available

Normal Visceral Adiposity

Courtesy of Wilfred Y. Fujimoto, MD.

 ADIPONECTIN
Adipose
Tissue

Adiponectin

 FFA
Oxidation
 FFA
↓ FFA Oxidation
↓ TG Influx

 Insulin ↓ Vascular
↓ Glucose ↓ TG
Sensitivity Inflammation
 Insulin
Sensitivity
(Ouchi N, et al, Curr Opin in Lipidol 2003)
 Increased visceral fat
Thiazolidinediones
-
Increased lipolysis

Increased TNF Decreased adiponectin

Increased FFA levels

- -
-
IR
 NO production
Endothelium
Shear stress Vasoconstriction

Adapted from Steinberg H et al. Diabetes. 2000;49:1231.

Atherogenic Dyslipidemia

Elevated Triglycerides > 150 mg

Low HDL <40 (M), <50 (F)
Increase in dense LDL type

Small Dense LDL (sLDL)

Increased Apolipoprotein
‘B’
Lipoprotein ‘a’ - Lp(a)
Abdominal Lipids and
Obesity Insulin BP control
Resistance
 Primary Secondary Drug Rx

Total Lifestyle  TG, sLDL PPAR -Fibrates

Calorie restriction  LDL & Apo B Statins full dose

Physical Activity  HDL Niacin, Aspirin

Change in Diet Attain goal BP ACE/ARB, other

 Statins, Fibrate
ACE/ARB
Exercise

Calorie 

Glitazones
Metformin
 Metabolic syndrome is a hidden volcano

 Evaluate every one >25 years of age for MS

 One manifestation – screen for all the rest

 WC must be measured routinely like taking BP

 Remember MS is the “PRE” for T2DM and CVD

 We should not wait till these killers develop

 There are effective Rx strategies