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

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

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

Increase
d
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)

Waist
Waist Circum
Circum

2 of
5

90
90 (M),
(M), 80
80 (F)
(F)
Triglycerides
Triglycerides

>150
>150 mg
mg

HDL
HDL

<40
<40 (M)
(M) << 50
50 (F)
(F)

Dysglycemia
Dysglycemia FPG
FPG >100
>100 or
or DM
DM
Hypertension
Hypertension

>130
>130 or
or 85
85

Rx.
Rx. for
for any
any of
of the
the above
above conditions
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
Increased lipolysis
lipolysis

Increased
Increased TNF
TNF
Increased
Increased FFA
FFAlevels
levels

IR

Shear stress

Decreased
Decreased adiponectin
adiponectin

Endothelium
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

(hepatic
(CETP) HDL
lipase)
TG

Apo A-1

CE (CETP) TG

Kidney

Insulin
LDL

sLDL

(lipoprotein or hepatic lipase)

Atherogenic Dyslipidemia
Elevated Triglycerides >
150Low
mg 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
Primary

Secondary
Secondary

Drug
Drug Rx
Rx

Total Lifestyle

TG, sLDL

PPAR

Calorie

LDL & Apo

-Fibrates

restriction

Physical

HDL

Activity

Attain goal BP

Statins full
dose
Niacin,

Change in

Aspirin

Diet

ACE/ARB,

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