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Metabolic Syndrome
Waist circumference:
* New ADA guidelines suggest >100mg/dl increases risk for Metabolic Syndrome
Life style
intervention
Excessive
food intake
Stress
Smoking
Obesity
Risk factor
modification
Hypertension
Diabetes
Dyslipidaemia
Atherosclerosis
Chronic
heart failure
Atherosclerosis
Arrhythmia
No. of deaths
(left axis)
% of all deaths
(right axis)
Male
Female
35
30
25
20
15
10
5
0
Dyslipidaemia
Hypertension
Abdominal
obesity
Metabolic Syndrome
Glucose intolerance
Insulin resistance
Metabolic syndrome
HDL-C
LDL-C
BP
Smoking
Insulin
Glu
TNF IL-6
Abdominal
Obesity
PAI-1
CARDIOVASCULAR DISEASE
TG
T2DM
25
20
25
20
*p<0.001
15
10
*
*
15
Prevalence (%)
*p<0.001
*
10
5
0
0
CHD
Isomaa et al 2001
MI
Stroke
All-cause
mortality
Cardiovascular
mortality
PAR (%)a
49
40
20
20
18
10
0
Abn Lipids
a
Abdom.
Obesity
HTN
Diabetes
Relative risk
2.5
2.0
1.5
2.06
2.31
2.44
1.27
1.0
0.5
0.0
<69.8
69.8-<74.2
74.2-<79.2
79.2-<86.3
86.3-<139.7
Wajchenberg 2000
Dyslipidemia
Hypertension
Abdominal
Obesity
Intra-Abdominal
Adiposity
Adapted from Eckel et al 2005
Glucose Intolerance
Insulin Resistance
Abdominal obesity
(High waist
circumference)
ct
e
r
i
Ind
Intraabdominal
adiposity
Direct
CV
disease
Glucose
Fed
Tg
Tg
Multiple secretory
products
Tg
Fasted
Muscle
Fatty acids
Glycerol
Liver
Pancreas
Lyon CJ et al 2003
Vasculature
suppression of
lipolysis by insulin
FFA
Insulin resistance
Dyslipidaemia
Pro-atherogenic
Heilbronn et al 2004; Coppack 2001;
Skurk & Hauner 2004
Secretion of
metabolically active
substances (adipokines)
PAI-1
Adiponectin
IL-6
TNF
Net result:
Insulin resistance
Inflammation
Agiotensinogen
IL-6
Inflammation
Hypertension
Insulin
TNF
Adipose
tissue
Atherosclerosis
Resistin
Leptin
Adipsin
(Complement D)
Adiponectin
FFA
Atherogenic
dyslipidaemia
Lactate
Plasminogen
activator inhibitor-1
(PAI-1)
Thrombosis
Type
2 diabetes
IL-6
in IAA
TNF
in IAA
PAI-1
in IAA
Anti-atherogenic/antidiabetic:
foam cells vascular remodelling
insulin sensitivity hepatic glucose output
Pro-atherogenic/pro-diabetic:
vascular inflammation insulin signalling
Pro-atherogenic/pro-diabetic:
insulin sensitivity in adipocytes (paracrine)
Pro-atherogenic:
atherothrombotic risk
Hepatic
insulin
resistance
Portal
circulation
Hepatic
glucose
output
FFA
Lipolysis
Small,
dense
LDL-C
TG-rich
VLDL-C
CETP,
lipolysis
Systemic
circulation
FFA: free fatty acids
CETP: cholesteryl ester
transfer protein
Low
HDL-C
Glucose utilisation
Insulin resistance
Short-term
stimulation
of insulin
secretion
FFA: Free fatty acids
Haber et al 2003; Zraika et al 2002
Long-term damage
to -cells
Decreased insulin
secretion
Environmental factors
Abdominal obesity
Adipokines
Adipocyte
Cytokines
Inflammatory markers
Insulin resistance
Tg
Metabolic syndrome
HDL
BP
Atherosclerosis
Plaque rupture/thrombosis
Cardiovascular events
Monocyte/
macrophage
Physical
inactivity
Excessive
food intake
Stress
Smoking
Obesity
Risk factor
modification
Disease
intervention/
secondary
prevention
Hypertension
Diabetes
Dyslipidaemia
Atherosclerosis
Chronic
heart failure
Atherosclerosis
Arrhythmia
Current Treatments
Weight reduction
TLC: Diet and Exercise
Lower BP goals
Lower LDL goals
Statins
Metformin
Aspirin therapy