metabolic syndrome

METABOLIC SYNDROME

PREVALENCE: in Pakistan• 46 – 48 % in overall population• 27 – 54 % of population have

dyslipemia and hyperlipidemia• 68 – 81 % of population has low

levels of HDL. • 50% are at high risk of metabolic

syndrome and hypertension. • the prevalence in reported to be

from 18% to 46% of the population.

SIGNS AND SYMPTOMS:• High blood sugar level : hyperglycemia• High cholesterol : hyperlipidemia,

Dyslipidemia• Obesity, with body fat concentration

around waist (visceral fat)• Increased blood pressure.• Atherosclerosis and high susceptibility of

CVD• Gout

SIGNS AND SYMPTOMS• Atherosclerosis and high susceptibility of CVD

• Gout -side effect of high blood sugar, associated with high cholesterol and obesity

• Other associated diseases and signs are:

• Hyperuricemia, ketonuria and acidosis

• Hyperinsulinemia

• Wasting of skeletal muscles

• Non Alcoholic Fatty liver

DIAGNOSIS:presence of three or more of these components:• Central or abdominal obesity• Fasting blood triglycerides greater than or

equal to 150 (mg/dL) of blood• Blood HDL cholesterol:

– Men - Less than 40 mg/Dl– Women - Less than 50 mg/dL

• Blood pressure greater than or equal to 130/85 mmHg• Fasting glucose greater than or equal to 100 mg/dL

RISK FACTORS:• Age.

• Race.

• Physical inactivity

• Diet. (high fructose drinks, high-fat diets)

• Sleep apnea

• Hormonal imbalance

• Stress. (upsetting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis).

• Obesity.

• Genetics

• Other diseases. schizophrenia or other psychiatric illnesses by exhausting the

insulin secretion and its transduction

• Smoking and narcotics addiction

PATHOGENESIS :• Metabolic syndrome is a cascade of

events indicating several metabolic anomalies occurring simultaneously in type II Diabetes Mellitus.

• Clinical features resulting from Insulin resistivity

INSULIN RESISTIVITY:• It is described as the gradual loss in the

sensitivity of the insulin receptor which is a transmembrane receptor 4 insulin receptor substrate 1-4 and cytosolic domains of tyrosine kinase (part of 2nd messenger system)

• lost expression of insulin receptors and distortion of signal transduction pathway of insulin in type II Diabetes.

Less no. of receptors on cell surface in obese people is found as compared to lean individuals • hyperinsulinemia (high conc. of insulin in plasma) develops which is itself toxic.

All functions reversed in Metabolic Syndrome

In Liver and Muscles:• Reduced Glucokinase activity• reduced expression of Glut receptors and co-

transporters• Limited uptake of glucose and and amino acid• Limited energy storing processes after

meal• Decrease in Glycogenesis• Decrease in Lipid Kinase activity

Energy crises in b/w meals• Activation of insulin antagonists• Glucagon • Lipase activation beta-oxidation of fats

instead of glycolysis• Accetoacetic acid accumulation• Acidosis • Blood PH reduces• Ketonemia and microalbuminurea• Muscles undergo wasting • Liver secretes abnormal fats resulting

Dyslipidemia

In Adipose Tissue• Reduced activation of Lipid Kinase

• Activation of Lipases

• Lipolysis

• FFAs and TGs in plasma

• Hypergylcemia

• Adipokines – leptin, TnF, IL-6, Resistin, adiponectin in plasma.

In All Cells:• Long term reduction in gene expression• DnA repair and synthesis • Reduced insulin like growth factors• Cell become prone to aging, inflammation• Increased prothrombic factors and cytokines• Reduce secretion of e nitric oxide Synthase • Vasoconstriction and High blood pressure

Special Thanks for illustrations and References:

• http://www.revespcardiol.org/en/aterogenesis-diabetes-resistencia-insulina-e/articulo/90113980/

• http://www.medbio.info/horn/time%203-4/homeostasis_2.htm

• http://themedicalbiochemistrypage.org/insulin.php• http://biocadmin.otago.ac.nz/fmi/xsl/bioc2/learnbitslect

ure.xsl?-db=BIOC2web.fp7&-lay=Lectures&-recid=5263&-find=

Presented by:

Sara siddiqui