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SYNDROME
Syndrome X
Cardiometabolic Syndrome
Cardiovascular Dysmetabolic Syndrome
Insulin-Resistance Syndrome
Metabolic Syndrome
Beer Belly Syndrome
Reavens Syndrome
etc.
Pharmacodynamics of insulin
* Affects all major metabolic pathways
carbohydrate, fat, protein
* Major target tissues are
liver, adipose, and skeletal muscle
* Decreases hepatic glucose production
decreases gluconeogenesis, glycogenolysis, ketogenesis,
(also glycogen synthesis)
Shepherd PR et al. Glucose transporters and insulin action. NEJM, July 22, 1999
Insulin Resistance
problem:
* Receptor:
Quantity / function
* Post-receptor (mostly):
Translocation of GLUT:
IRS (insulin receptor substance) / kinase
Synthesis of GLUT
Liver
IR
Adipose
tissue
Muscle
Glucose output
Glucose uptake
Glucose uptake
Hyperglycemia
Prevalence
Risk Factors
Apple
Pear
Age
Race
Obesity
History of
diabetes
Other
diseases
Dyslipidemia
Hypertension/
Microalbuminuria
Atherosclerosis
McFarlane S, et al. J Clin Endocrinol Metab 2001; 86:713718.
Genetic
Influences
Insulin
Resistance
Environmental
Influences
Hyperlipidemia
Glucose
Intolerance
Increase
Triglycerides
Decreased
HDL
Cholesterol
Increased
Blood
Pressure
Small Dense
LDL
PAI-1
Coronary Heart
Disease
Adult
Adult life
life
Sedentary
Sedentarylifestyle
lifestyle
Dietary
Dietaryfactors
factors
Metabolic
Metabolic
Syndrome
Syndrome
Genes
Genes
CARDIOVASCULAR
CARDIOVASCULAR
DISEASE
DISEASE
BMI
BMI
Central
CentralAdiposity
Adiposity
Insulin
Insulin Resistance
Resistance
Hyperinsulinemia
Hyperinsulinemia
Glucose
Glucose
Metabolism
Metabolism
Glucose
intolerance
Uric
UricAcid
Acid
Metabolism
Metabolism
Uric acid
Urinary
uric
acid clearance
Dyslipidemia
Dyslipidemia
TG
PP lipemia
HDL-C
PHLA
Small, dense LDL
Hemodynamic
Hemodynamic
SNS activity
Na retention
Hypertension
CORONARY
CORONARY HEART
HEART DISEASE
DISEASE
Adapted from Reaven G. Drugs. 1999;58 (suppl):19-20
Novel
Novel Risk
Risk
Factors
Factors
CRP
PAI-1
Fibrinogen
WHO
EGIR
ATPIII
Main criteria
Insulin resistance
OR
DM / IGT / IFG
Main criteria
Insulin resistance
Other components
1)Blood pressure
140/90
2)Dyslipidemia
3)Central obesity
4)Microalbuminura
(two or more)
Other components
1)Hyperglycemia
2) Blood pressure
140/90
3)Dyslipidemia
4)Central obesity
(two or more)
1)Abdominal
obesity
2)High triglycerides
3)Low HDL
cholesterol
4)Blood pressure
130/85
5)High fasting
glucose
(three or more)
Reduced HDL
cholesterol
Adiponectin
BP
Insulin
Resistance*
TG
Abdominal
Obesity
Microalb
HDL
PAI-1
Apo B
Little LDL
OGTT
IFG &
Diabetes
MANAGEMENT:
Life-Style Modification
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: Brisk walking - 30 min./day
10% reduction in body wt.
Drug Treatment of
The Metabolic Syndrome
Type 2 Diabetes
Hyperinsulinemia
IGT
Dyslipidemia
Hypertension
Coagulation
abnormality
IGT = impaired glucose tolerance