Pugud Samodro

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

IR

Smoke

BB

MS

CVD

DM

Insulin Resistance

Obesity

Metabolic Syndrome

Diabetes

2x

4x

Cardio Vascular Disease (CVD)

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

Insulin
Resistance
Inadequate
Insulin prod
Type 2 DM

CKD,DPN

Hyper
Insulinemia

CAD

Metabolic
Syndrome
HT, Stroke,
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

Dyslipidemia

IGT, IFG

ED, Vessel

Increased
CV Risk

Pro Thrombotic

Hypertension

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

Hypertension
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
Measure

WHO
(1998)

EGIR
(1999)

ATP III
(2001)

AACE
(2003)

Insulin
Resistance

IGT,IFG,T2DM or
Lower insulin sensitivity
Plus any 2 of the following

Plasma Insulin
> 75th percentile
Plus any 2 of the
following

None, But any 3 of

the following 5
Features

IGT or IFG plus any

of following based on
clinical judgement

Body
Weight

Men : WHR > 0.90

Women : WHR > 0.85
And/or BMI > 30 kg/m2

WC >94 cm in men
Or
>80 cm in women

WC > 102 cm in men

Or
> 88 cm in women

BMI > 25 kg/m2

Lipid

TG> 150 mg/.dl or

HDL-C<35 mg/dl in men
Or < 39 mg/dl in women

TG >150 mg/dl &

or
HDL-C < 39 mg/dl
In men or women

TG> 150 mg/.dl or

HDL-C<40 mg/dl in men
Or < 50 mg/dl in women

TG> 150 mg/.dl or

HDL-C<40 mg/dl in
men
Or < 50 mg/dl in
women

Blood
Pressure

> 140/90 mmHg

> 140/90 mmHg

or non hypertension

> 130/85 mmHg

130/85 mmHg

Glucose

IGT, IFG or T2DM

IGT or IFG
(but not diabetes)

IGT or IFG
(but not diabetes)

Other

Microalbuminuria

> 110 mg/dl

(Include diabetes)
FPG >110 mg/dl (2001)
FPG > 100 mg/dl (2004)

IDF
(2005)
None

Increase WC
(population specific)
Plus any 2 of the
following

TG> 150 mg/.dl or

HDL-C<40 mg/dl in men
Or < 50 mg/dl in women

> 130 mmHg systolic or

> 85 mmHg diastolic or
Non hypertention Rx
> 100 mg/dl
(include diabetes)

Other features of
Insulin resistance
(PCOS,T2DM etc)

(Grundy et al, 2005)

 90 (M), 80 (F)

Waist Circum

2 of 5

Triglycerides

>150 mg

HDL

<40 (M) < 50 (F)

Dysglycemia FPG >100 or DM

Hypertension

>130 or 85

Rx. for any of the above conditions

Features

Insulin Resistance

Hyperglycemia

PPBG, Usually FBG is N

Obesity, WC, ACN

BMI > 23, WC > 90, ACN+

TG, HDL, sLDL

Dyslipidemia Present

Cluster of metabolic factors

Metabolic Syndrome

Hypertension (>130/80)

Usually is a feature

Recent weight change

Increase

Fasting C peptide / Insulin

Increased (HOMA)

Treatment

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
TG

Insulin
Sensitivity

FFA
Influx

FFA
Oxidation

Glucose TG
Insulin
Sensitivity

(Ouchi N, et al, Curr Opin in Lipidol 2003)

Vascular
Inflammation

Increased visceral fat

Thiazolidinediones

Increased lipolysis

Increased TNF
Increased FFA levels

IR

Shear stress

Decreased adiponectin

Endothelium

NO production
Vasoconstriction

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

Fat Cells

Liver
FFA

IR X

CE

TG
Apo B
VLDL

VLDL

(CETP) HDL

(hepatic
lipase)

TG

Apo A-1

CE (CETP) TG

Kidney
Insulin
LDL

sLDL

(lipoprotein or hepatic lipase)

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
Obesity

Insulin
Resistance

Lipids and
BP control

Primary

Secondary

Drug Rx

PPAR -Fibrates

Total Lifestyle

TG, sLDL

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

DEMI LOVATO NEON LIGHTS