1 / 28

New Insights and Therapies for the Metabolic Syndrome

New Insights and Therapies for the Metabolic Syndrome. Thomas Alexander, M.D. New Features of ATP III. Identification of metabolic syndrome Abdominal obesity; men more than 40 inches; women more than 35 inches Triglycerides; >150 mg HDL cholesterol for men <40 mg; women <50 mg

norwood
Download Presentation

New Insights and Therapies for the Metabolic Syndrome

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. New Insights and Therapies for the Metabolic Syndrome Thomas Alexander, M.D.

  2. New Features of ATP III • Identification of metabolic syndrome • Abdominal obesity; men more than 40 inches; women more than 35 inches • Triglycerides; >150 mg • HDL cholesterol for men <40 mg; women <50 mg • Blood pressure >130/85 • Fasting glucose >110

  3. Definition of Metabolic Syndrome • Insulin resistance • Life style especially obesity • Sub clinical inflammation • Diabetes and prior myocardial infarction carry the same mortality risk

  4. Risk Factors – Not routinely measured • Insulin resistance • Small dense LDL • Endothelial dysfunction • Abnormal sympathetic nervous activity • Prothrombotic markers – fibrinogen • Proinflamatory markers

  5. Features of Diabetes Mellitus • Hyperglycemia - Secondary to defect in insulin secretion or insulin action or both • Diagnosis – Fasting plasma glucose of 110 to 126 – pre diabetes • Blood sugar > 126 or plasma glucose > 200 on a GTT.

  6. Etiology • Type 1 Diabetes – β-cell destruction due to immune mediated or idiopathic • Type 2 Diabetes – with relative insulin deficiency to a predominant secretory defect with insulin resistance • Gestational • Genetic defects in β–cell function • Drug induced • Infections

  7. Type 1 Diabetes Mellitus • Insulin deficiency – secondary to β-cell destruction • Markers – islet cell auto antibodies, auto antibodies to insulin, auto antibodies to glutamic acid decarboxylase

  8. Type 2 Diabetes Mellitus • Has strong genetic predisposition • Obesity can cause some insulin resistance • Ketoacidosis seldom occurs • Hyperglycemia may develop gradually • At increase risk for micro & macro vascular complications • Increase levels of tumor necrosis factor-α and free fatty acids produce insulin resistance

  9. Progress of Pathogenic Type 2 Diabetes Mellitus Initiation Factors Progression Factors -Insulin resistance -Obesity -Insulin secretion -β-cell Toxins -β-cell capacity genes -Diet/toxins -Obesity genes -Activity/age Type 2 Diabetes Failing insulin secretion, glucose desensitization of β-cell, decreased glucose sensitivity

  10. Treatment of Diabetes Mellitus Type 2 • Oral anti diabetic agents 1. Sulfonylureas and meglitinides – augment insulin levels 2. Metformin – inhibit hepatic gluconeogenesis and glycogenolysis, improve insulin sensitivity 3. Thiazolydinediones – suppress expression of specific genes & lower triglycerides 4. Acarbose – reduces absorption of CHO 5. Combination Therapy preferred 6. Insulin Therapy

  11. Complications • Acute -Diabetic ketoacidosis, dehydration, K depletion, cerebral edema, non ketotic hyperosmolar coma • Long Term -Cardiovascular disease causes 75% of disabilities and deaths in diabetes caused by insulin resistance, hypertrigl: HTN, low HDL. Target LDL < 100, triglycerides < 150, HDL >50, BP < 130/80 -PVD -Micro vascular – diabetic retinopathy, nephropathy, neuropathy, cardiovascular autonomic neuro: GI neuro: -Diabetic foot > 50% of all non traumatic complications in U.S. is secondary to diabetes

  12. Macro Vascular Complications • Mortality from CVD 2 fold > in men 4 fold > in women • 7 yr incidence of MI = non DM with MI • Reduction in BP, reduced MI by 21% and stroke by 44% • Cholesterol lowering, reduced CVD by 24% • In secondary prevention reducing cholesterol, reduced CVD by 42%

  13. Hyperlypoproteinemia Exo Endo LDL -Dietary fat LDL LDL Receptor Intestine Extra, Tissue Capillary FFA Remnants VLDL HDL Adipose tissue IDL and muscle Capillary Plasma FFA Adip: Tissue Liver Endo: Chol: Diet: Chol:

  14. ATP III Guidelines • Step 1 -Determine lipoprotein levels after 9 to 12 hour fast -LDL Cholesterol – Primary target, <100 optimal, 100-129 near optimal, 130-159 borderline high, 160-189 high, >190 very high -Total Cholesterol - <200 desirable, 200-239 borderline high, >240 High -HDL Cholesterol - <40 low

  15. Step 2 -Identify presence of atherosclerotic disease -Clinical CHD -Carotid artery disease -PVD -AAA

  16. Step 3 -Determine major risk factors other than LDL -Cigarette smoking -Hypertension, BP >140/90 -Low HDL -Family history of premature CHD -Age, Men >45 & women >55 -HDL Cholesterol >60 – count as a negative risk factor

  17. Step 4 - If 2+ risk factors (other than LDL) present without CHD assess 10 year CHD risk (see Framingham tables) -Three levels of 10 year risk - >20% - CHD risk equivalent - 10 to 20% - <10%

  18. Step 5 -Determine risk category -Establish LDL goal of therapy -Determine need for therapeutic lifestyle changes -Determine level for drug consideration

  19. LDL Cholesterol Goals and Cut points for TLC and Drug Therapy in different Risk Categories

  20. Step 6 -Initiate TLC in LDL is above goal -TLC Diet: -Saturated fat <7% of calories, cholesterol <200 mg/day -Weight management -Increased physical activity

  21. Step 7 -Consider drug simultaneously with TLC for CHD -Consider adding drug to TLC after 3 months for other risk categories

  22. Drugs Affecting Lipoprotein Metabolism

  23. Step 8 -Identify metabolic syndrome and treat after 3 months of TLC Risk Factor Defining Level Abdominal obesity Waist Circumference Men >102 cm Women >88 cm Triglycerides > 150 mg/dL HDL cholesterol Men < 40 mg/dL Women < 50 mg/dL Blood Pressure > 130/ >85 mmHg Fasting Glucose > 110mg/dL

  24. Step 9 -Treat elevated triglycerides ATP III Classification of Serum triglycerides <150 Normal 150-199 Borderline 200-499 High >500 Very high Treatment of elevated triglycerides -Reach LDL goal -Intensify weight management -Increase physical activity Comparison of LDL Cholesterol & Non-HDL Cholesterol Goals for 3 risk Categories

  25. If triglycerides 200-449 mg/dL after LDL goal is reached, consider adding drug if needed to reach non-HDL goal: -intensify therapy with LDL-lowering drug -add nicotinic acid of fibrate to further lower VLDL If triglycerides >500 mg/dL, first lower triglycerides to prevent pancreatitis: -very low-fat diet -weight management and physical activity -fibrate or nicotinic acid When trigly. <500 mg/dL, turn to LDL-lowering therapy Treatment of low HDL cholesterol -First reach LDL goal -Intensify weigh management and increase physical activity -If trigly. 200-449 mg/dL, achieve non-HDL goal -If trigly. <200 mg/dL in CHD or CHD equiv. consider nicotinic acid or fibrate.

  26. Estimate of 10 yr Risk for Men (Framingham Point Scores)

  27. Diet for the Metabolic Syndrome • Primary emphasis is to reduce saturated fats • Total fat should range 25-30% for most cases • Those with metabolic syndrome avoid very high fat intake also avoid very low fat intake (low HDL & high TG) • Total fat intake can range from 30-35% if extra fat in unsaturated • May reduce some lipid and non lipid risk factors • Clinical judgment required

  28. QUESTIONS????

More Related