metabolic syndrome pathophysiology

Metabolic Syndrome: Pathophysiology International Diabetes Center What to call the syndrome? • • • • • • Reaven’s Syndrome Deadly Quartet Insulin Resistance Syndrome Syndrome X Dysmetabolic Syndrome X Multiple Metabolic Syndrome • Metabolic Syndrome International Diabetes Center Clinical Identification Metabolic Syndrome Any Three of the Following: Risk Factor Defining Level Abdominal obesity Men Women Waist circumference >40 in (>102 cm) >36 in (90 cm) >32 in (80 cm) >35 in (>88 cm) Triglycerides ≥150 mg/dL (1.7 mmol/L) HDL-C Men Women 18 Years of Age 25 25% 20 20% 15 10 14% Without Baseline Microalbuminuria With Baseline Microalbuminuria 14% No Diabetes (n=5545) Diabetes (n=3498) Patients followed avg 4.5 years as part of Heart Outcomes Prevention Evaluation (HOPE) Study Gerstein et al., JAMA 2001:286:421-426 International Diabetes Center Components of the Metabolic Syndrome Hyperglycemia Dyslipidemia Hypertension Insulin Resistance Abnormal vascular behavior Thrombotic Risk Thrombotic Risk Fat Mass International Diabetes Center Abnormal Vascular Behavior in the Metabolic Syndrome • Impaired vasodilatation due to endothelial dysfunction • Potential causes – Hyperglycemia – Dyslipidemia-high levels of FFA impairs Nitric oxide synthase activity – Impaired insulin signaling International Diabetes Center Components of the Metabolic Syndrome Hyperglycemia Dyslipidemia Hypertension Resistance Abnormal Thrombotic risk vascular behavior Fat Mass International Diabetes Center Thrombus International Diabetes Center Thrombotic Risk in Metabolic Syndrome Elevated fibrinogen levels – Plasma protein secreted by liver – Converted into fibrin during clotting of blood – Increase correlated with BMI, WHR, triglycerides, and low HDL Fibrinogen Fibrin Thrombus Imperatore et al Diabetes Care 1998;21:649-654 Trovati and Anfossi, J Diabetes Comp 2002;16:35-40 International Diabetes Center Thrombotic Risk in Metabolic Syndrome Platelet dysfunction – – – – Increased platelet adhesiveness Increased platelet aggregation Increased production of vasoconstrictors (prostanoids) Mechanism– increased glycosylation of platelet membrane proteins G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G Thrombus Imperatore et al Diabetes Care 1998;21:649-654 Trovati and Anfossi, J Diabetes Comp 2002;16:35-40 International Diabetes Center Thrombotic Risk in Metabolic Syndrome Elevated plasminogen activator inhibitor (PAI-1) – Associated with increased risk of coronary vascular events – Causes formation of unstable plaques Plasminogen Activators Plasminogen (inactive) PAI-1 Plasmin (active) Fibrinolysis Juhan-Vague et al., Circulation 1996;94:2057-2063 International Diabetes Center Additional Components of Metabolic Syndrome • Acanthosis Nigricans • Polycystic Ovary Syndrome (PCOS) • Hyperuricemia International Diabetes Center Acanthosis Nigricans on the Neck International Diabetes Center Polycystic Ovary Syndrome (PCOS) • Clinical Features – Chronic anovulation (infertility) – Hyperandrogenism • Elevated total or free testosterone • Hirsutism or acne • Affects 5% to 10% of women of childbearing age in the U.S • Most common cause of female infertility (approximately 50% to 60%) • Insulin resistance and hyperinsulinemia occurs in both obese and non-obese women with PCOS International Diabetes Center Summary: Components of the Metabolic Syndrome Hyperglycemia IFG/IGT Type diabetes IFG/IGT Type diabetes Dyslipidemia PCOS CVD Hypertension Insulin Resistance LDL - Trigs - HDL LDL - Trigs - HDL Microalbuminuria Microalbuminuria ↑ Uric acid TNF α - FFA TNF α - FFA Abnormal Thrombotic risk ↑PAI-1 ↑ Fibrinogen vascular behavior Acanthosis PAI-1 ↑ Fibrinogen Endothelial dysfunction Endothelial dysfunction ↑Platelet aggregation Platelet aggregation Fat Mass Visceral // Subcutaneous Visceral Subcutaneous Obesity Obesity International Diabetes Center ...What to call the syndrome? • • • • • • Reaven’s Syndrome Deadly Quartet Insulin Resistance Syndrome Syndrome X Dysmetabolic Syndrome X Multiple Metabolic Syndrome • Metabolic Syndrome International... the Metabolic Syndrome Hyperglycemia Dyslipidemia Hypertension Insulin Resistance Abnormal Thrombotic Risk vascular behavior Fat Mass International Diabetes Center Components of the Metabolic Syndrome. .. Obesity In Metabolic Syndrome • Central obesity is critical factor – Waist to hip ratio >1 – Waist >40 inches in men – Waist >35 inches in women • Abdominal adipose tissue is more metabolically