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Training. Metabolic S yndrome November 2014. Contents. 1. Metabolic Syndrome – General information a) Symptoms of Affluent Society b) The 4 Core Components of Metabolic Syndrome (M.S.) c) Metabolic Syndrome d) “Obesity ” e) “Central Obesity”
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Training Metabolic Syndrome November 2014
Contents • 1. MetabolicSyndrome – General information • a) Symptoms ofAffluent Society • b) The 4 Core Components of Metabolic Syndrome (M.S.) • c) Metabolic Syndrome • d) “Obesity” • e) “Central Obesity” • f) Waist Circumference (IDF 2006) • g) Abdominal Obesity IDF 2006 • h) Abdominal Obesity & Visceral Fat • i) BMI – WHO Definition of Obesity • j) What Shape Are You In? • k) Multiple Complications From Obesity • l) Obesity-Associated Morbidity • m) WHO Global Health Risk Report • n) Obesity Trends Among U.S. Adults • o) Estimated Overweight Prevalence • 2. Definitions of Metabolic Syndrome • a) Definitions of Metabolic Syndrome • b) Clinical Diagnosis of Metabolic Syndrome • c) Worldwide Definition of IDF 2006 • d) Worldwide Def. – Children & Adolescents • e) “Platinum Standard” Definition • f) IDF: Worldwide Definition • g) Prevalence of Metabolic Syndrome • h) Prevalence of individual Abnormalities • 3. Pathogenesis • a) Pathogenesis of Metabolic Syndrome • b) Adipose Tissue: An Endocrine Organ • c) Elevated NFA contribute to • d) Pathogenesis: Vicious Circle • e) History of Typ 2 Diabetes (T2DM) • f) Pathophysiology of Hyperinsulinaemia • g) IDF and Novel CVD-Risk Factors • h) CVD Mortality Increase • i) What are Cardiovascular Diseases? • j) Deaths of CVD • k) Obesity – Development of NASH • 4. Summary Metabolic Syndrome • 5. Primary Intervention for Met. Syndrome • a) Life-Style Modifications – Important? • b) Weight Loss – Important? • 6. Secondary Intervention (IDF) • 6.1. AtherogenicDyslipidaemia • a) Treatment of Atherog. Dyslipidaemia • b) Simvastatin • c) Pleiotropic Effects of Statins • d) Equivalent Daily Doses for Statins • e) LDL Reduction (%) of Different Statins in Different Doses • f) Summary of Evidence • g) Simva-Denk • h) FDA Announcement 2/28/2012
Contents • 6.2. Elevated Blood Pressure • a) Treatment of Elevated BP • b) Losar-Denk (ARB) • c) Ena-Denk (ACEI) • d) Captopril-Denk (ACEI) • 6.3. Insulin Resistance and Hyperglycaemia • a) Treatment of IR and Hyperglycaemia • b) Diabetes Prevention Program – DPP • c) Treatment of IR and T2DM – Summary • d) Metformin Denk • e) Glimepiride Denk • f) Treatment of ProthromboticState • g) Clopi-Denk • 6.4. Traditional Treatment Approach • 6.5. New Treatment Approach • a) Treatment of Atherog. Dyslipidaemia • b) Treatment of Elevated BP • 7. DenkPharma Met. Syndrome Portfolio • 8. Take Home Messages • 9. Train the Brain – Quiz • 10. References Click on thetitle toredirecttothepageswithfurtherinformation! Click toreturntothispage!
1a) Symptoms of Affluent Society? CVD Syndrome Insulin Resistance Syndrome Dysmetabolic Syndrome DeadlyQuartet 2001 ICD-9-CM Diagnosis Code 277.7 „Dysmetabolic Syndrome X “ Cardiometabolic Syndrome Syndrome X Reaven´s Syndrome MetabolicSyndrome (2013 ICD 10) Plurimetabolic Syndrome
b) The 4 Core Components ofMetabolicSyndrome (M.S.) Main Causes 1.Central Obesity 2.Insulin resistance 2.Insulin resistance 2.Insulin resistance X Several risk factors cluster together => => „Syndrome“ 3.Hypertension 4.Dyslipidaemia 4.Dyslipidaemia 4.Dyslipidaemia “Deadly Quartet” and “Syndrome X”
c) Metabolic Syndrome (1) “The clustering of cardiovascular disease risk factors typifies the metabolic syndrome and is now considered to be the driving force for a new CVD epidemic.” (International Diabetes Federation IDF) => A multiplex riskfactorfor CVD
3xrisk to develop CVD 2xriskto develop CVD c) MetabolicSyndrome (2) • Other potentiating effects • 3x risk to have • a heart attack or stroke • 2x risk to die from • 5x risk to develop • T2DM • >35% of worlds adult population have M.S.
d) „Obesity“ “Obesity itself has become a life-long disease, not a cosmetic issue, nor a moral judgment—and it is becoming a dangerous epidemic.” (1998)1 “In response to ….the American Heart Association (AHA) has reclassified obesity as a major, modifiable risk factor for coronary heart disease.“(1998)2 “Obesity is a major risk factor for cardiovascular disease and has been strongly associated with insulin resistance. Weight loss can improve cardiovascular risk, decrease insulin concentration and increase insulin sensitivity. Obesity and insulin resistance also have been associated with other risk factors, including high blood pressure.” (2012)3
e) „Central Obesity“ (1) Waist circumference! 94 80
e) „Central Obesity“ (2) Waist circumference!
f) WaistCircumference (IDF 2006) Basic requirement for worldwide “Metabolic syndrome”- definition! “Gender and, for the first time, ethnicity specific cut-off points for central obesity as measured by waist circumference are included.” (IDF)
g) Abdominal Obesity IDF 2006 A better predictor of development of the Met. Syndr. than BMI
h) Abdominal Obesity & VisceralFat (CT) Normal weight (CT) adiposity
i) BMI – WHO Definition ofObesity Body Mass Index The International Classification of adult underweight, overweight and obesity according to BMI
j) What Shape areyouin? Height (feet and inches) Height (feet and inches) Height (feet and inches) Underweight<18,5 Normal weight 18,5 -24,9 Weight (kilograms) Weight (kilograms) Weight (pounds) Weight (pounds) Overweight 25-29,9 Obese > 30 Height (centimeters) Height (centimeters) BMI = weight/height2
k) Multiple ComplicationsfromObesity Metabolic syndrome Insulin resistance syndrome Diabetes Fatty liver, abnormalities of liver function and inflammation Hypertension Infertility Gout Gall bladder disease Polycystic ovary syndrome • Arthritis and inflammation Arteriosclerosis (Stroke/Heart attack) several cancers (endometrial, breast, and colon) damage to joints (ankle, knees, hips)/osteoarthritis Sleep apnoea (fat enclosure in pharynx) Depression Anxiety, social stigmatisation risk of suicide BMI ↑ →risk for these noncommunicable diseases ↑
n) Obesity Trends Among U.S. Adults (1) BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 5’4” person) • About one-third of U.S. adults (33.8%) are obese.Approximately 17% (or 12.5 million) of children and adolescents aged 2—19 years are obese.
o) EstimatedOverweightPrevalence Estimatedoverweight & obesity (BMI ≥ 25 kg/m2) prevalence, Females, Aged 15+, 2010
c) Worldwide Definition of IDF 2006 Men: > 94 cm Women: > 80 cm or RX for high TG or RX for low HDL or RX for high BP or RX for high glucose 94 80 => Narrow confines for early detection of each risk factor! => Narrow confines for early detection of each risk factor!
e) „Platinum Standard“ Definition (2) Additional metabolic measurements for research (of IDF 2006): „….The consensus group has highlighted a number of other parameters that appear to be related to the metabolic syndrome (table 3) which should be included in research studies to help determine the predictive power of these extra criteria for CVD and/or diabetes.... ...The use of these additional factors in the research will also allow further modification of the definition if necessary and the validation of the new clinical definition in different ethnic groups.”
f) IDF: Worldwide Definition Addresses worldwide clinicians, researchers and epidemiological studies.
g) PrevalenceofMetabolic Syndrome (1) => UsingIDF criteria (?) => Nowadays it affects 35% of the adults (American Heart Assoc. in 11/2011)2
g) PrevalenceofMetabolic Syndrome (2) Prevalenceworldwide in adults IDF facts: in childrenandadolescentsincreasingnumbers!
g) PrevalenceofMetabolic Syndrome (3) • Higher prevalenceofmetabolicsyndrome in certainethnicgroups: • Hispanicand Native Americans • Asians (esp. South Asians)
g) PrevalenceofMetabolicSyndrome (4) IDF vs. ATP III
h) Prevalenceof Individual Abnormalities Prevalenceof individual abnormalitiesofmetabolicsyndrome* 8814 adultsdiff. ethnicity IDF higher
3a) PathogenesisofMetabolic Syndrome • Elevated plasma glucose or/and • hyperinsulinaemia giveriseto Underlying risk factors Metabolic risk factors and abnormalities • Elevated high blood pressure • Endothelial dysfunction • Excess ovarian testosterone production • Atherogenic dyslipidaemia • Hemodynamic changes, manifestation of a prothrombotic state and proinflammatory state • Insulin resistance * Sturatedfatandcholesterol
b) AdiposeTissue: An EndocrinOrgan Adipocytokines (adipokines) Antiatherogenic Atherogenic CRP IL-1,6,8, 10,18, PAI-1 Angiotensinogen Leptin Resistin MCP-1 TNF-α Adiponectin glucose flux (decreased gluconeogenesis, increased g.uptake), lipid catabolism (ß-oxidation,TGclearence), protection from endothelial dysfunction, insulin sensitivity, weight loss, control of energy metabolism CRP: C-reactiveprotein IL: Interleukin MCP-1: Monocytechemoattractant protein-1 TNF: Tumor-necrosisfactor PAI-1: Plasminogenactivator inhibitor-1
c) Elevated NEFA contributeto Hypertension/CVD Atherogenesis Dyslipidaemia/CVD Nonalcoholic fatty liver disease NFLD; NASH Insulin resistance/T2DM/CVD CVD/ T2DM overloadedorgans/tissues ectopic lipid accumulation multiple adipocytokines
d) Pathogenesis: Vicious Circle Downregulation of Insulinreceptors Increased requirements of Insulin Overweight, Genetics, Ageing, Physical inactivity, Hyper-alimentation Hyperinsulinism Insulin resistance Person is constantly hungry → Obesity Hyperglycaemia (worn out ß-cells!), high risk of developing T2DM Dyslipidaemia, Hypertension and Metabolic Syndrome Very high risk of developing AteriosclerosisandCardiovasculardisease! Secretion of Insulin
e) Historyof Typ 2 Diabetes (T2DM) Physical damages started already!! ß-cell-dysfunction At risk forT2 DM
f) PathophysiologyofHyperinsulinaemia Insulin triggers -Insulin resistance e.g.in liver, skeletal muscle, adipose/fat tissue -Synthesisof FFA, Triglycerides, Cholesterol -Lipoprotein-Lipase activity -Cellular uptake of FFA, cholesterol rich lipoproteins in vascular walls -Proliferation of smooth muscle tissue -Sodium reabsorption in kidneys -Stimulation of sympathic system -endothelial dysfunction Dysglycaemia or Diabetes Mellitus Dyslipidaemia Hypertension Atherosclerotic cardiovascular disease (ASCVD) • Hyperinsulinaemic individuals are at risk for developing Diabetes, • Dyslipidaemia, Hypertension and ultimately CVD
h) CVD MortalityIncrease WithnumberofMetabolicSyndrome riskfactors
i) WhatAre CardiovascularDiseases? Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels and include: Coronary heart disease – disease of the blood vessels supplying the heart muscle Cerebrovascular disease - disease of the blood vessels supplying the brain Peripheral arterial disease – disease of blood vessels supplying the arms and legs Rheumatic heart disease – damage to the heart muscle and heart valves from rheumatic fever, caused by streptococcal bacteria Congenital heart disease - malformations of heart structure that exist at birth Deep vein thrombosis and pulmonary embolism – blood clots in the leg veins, which can dislodge and move to the heart and lungs. Heart attacks and strokes - usually acute events and are mainly caused by a blockage that prevents blood from flowing to the heart or brain.(CHD/CerebroVD) - More people die annually from CVDs than from any other cause! - An estimated 17.3 million people died from CVDs in 2008, representing 30% of all global deaths. By 2030, almost 23.6 million people will die from CVDs.
j) Deathsof CVD IHD: characterized by ischaemia (reduced blood supply) of the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries) => “CVD”! Cerebrovascular disease: means Stroke => Caused by “AS(C)VD”!
k) Obesity – Development of NASH => Transplantation => Scar tissue makes liver hard,unable to work properly; jaundiced skin =nonalcoholic fatty liver disease (NAFLD). Scar tissue forms, liver cell injury occurs NASH causeliverenlargement
IDF Worldwide Definition focuses abdominal obesity => adipose tissue is emerging as an endocrine organ and leads to different metabolic disorders! 4. Summary MetabolicSyndrome • Expansion of visceral adipocytes leads to release of many “bad” adipokines, decreased sectretion of “good” adiponetcin, low HDL, high LDL, and a lot of other cascades.... • Elevated FFA levels act on liver, heart, skeletal muscle and other organs topromote hypertension, dyslipidaemia, insulin resistance, cancers, NASH, CVD, T2DM and METABOLICSYNDROME...
5. Primary Intervention for Met. Syndrome IDF recommends “healthy lifestyle promotion”: moderate calorie restriction (to achieve a 5–10 per cent loss of body weight in the first year) moderate increase in daily physical activity change in dietary composition Increase vegetable, fruits, legumes Decrease fat and salt Fish (Omega 3 fatty acids!) Poultry Whole grains No/reduced alcohol, smoking cessation
a) Life-Style Modifications – Important? Physical activity and exercise Improves CV fitness, weight control, sensitivity to insulin (+ its cascade), reduces incidence of diabetes (+ complic.) makes you feel and look better! Weight loss Improves lipids and liver function, sensitivity to insulin, BP levels, reduces incidence of diabetes =>makes you feel and look better! • Goals: • - brisk walking – 30 min /day (“run your risks of diabetes • and CVD away!”) • - 5 - 10 % reduction in body weight in the first year • - BMI ≤ 25