Metabolic syndrome november 2014


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Macrovascular complications in diabetes

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  • Atherosclerosis: An Inflammatory Disease*
    Atherosclerosis, once regarded largely as a disorder of lipid accumulation, is now generally viewed as an inflammatory disease. The process begins with endothelial dysfunction caused, for example, by modified LDL, an infectious microorganism, or free radicals associated with cigarette smoking. Modified LDL is a major cause of endothelial injury in patients with type 2 diabetes and results from such factors as oxidation and glycation.
    Post-insult endothelial changes include increased leukocyte adhesion and migration into the arterial wall, increased permeability to lipoproteins and other plasma constituents, a switch from anticoagulant to procoagulant activity, and formation of cytokines, growth factors, and vasoactive molecules. As the inflammation continues, circulating monocytes and lymphocytes migrate into the subendothelial space, and macrophages ingest oxidized LDL and are transformed into foam cells. The resulting fatty streak is augmented by migrating/proliferating smooth muscle cells and adherent / aggregating platelets to form an intermediate atherosclerotic lesion. Activation of T lymphocytes and macrophages also leads to the release of hydrolytic enzymes, cytokines, chemokines, and growth factors, which induce further damage. Eventually, a fibrous cap, which represents a healing response, will form over the mixture of leukocytes, lipid, and debris to wall off the lesion from the lumen. The core of such an advanced lesion may become necrotic. Subsequent thinning and rupture of the fibrous cap appears to be caused by the continued influx and activation of macrophages. Their release of metalloproteinases and other proteolytic enzymes causes degradation of the matrix, followed by possible hemorrhage, thrombus formation, and arterial occlusion.
    Ross R. N Engl J Med. 1999;340:115-126.
    *An animated version of this slide is located in the folder “Animated Slides.”
  • In addition to type 2 diabetes, insulin resistance is associated with the development of a broad spectrum of clinical conditions. These include hypertension, atherosclerosis, dyslipidemia, decreased fibrinolytic activity, impaired glucose tolerance, acanthosis nigricans, hyperuricemia, polycystic ovary disease, and obesity.
    Adapted from Consensus Development Conference of the
    American Diabetes Association. Diabetes Care. 1998;21:310-314.
  • Malik and colleagues demonstrated that the cardiometabolic risk factors associated with metabolic syndrome increase the CVD mortality rate. Relative to an individual with no metabolic syndrome risk factors, having 1 to 2 risk factors increased a patient’s hazard ratio by more than 70%. Persons with metabolic syndrome (having ≥3 of the 5 risk factors) were found to have a hazard ratio of 2.71. The ratio increased with the onset of type 2 diabetes, CVD, and was greatest in persons with existing CVD and T2DM.
    Malik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110:1245-1250.
  • 1. Paolisso G, Howard BV. Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes mellitus. Diabet Med 1998; 15(5):359
    2. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104(6):787-94
    3. Maedler K, Spinas GA, Lehmann R, et al. Glucose induces beta-cells apoptosis via upregulation of the Fas receptor in human islets. Diabetes 2001; 50(8):1683-90
    4. DeFronzo RA, Bonadonna R, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992; 15(3):318-68
    1. Weyer C, Bogardus C, Mott DM et al. J Clin Invest 1999; 104: 787–94.
    2. UK Prospective Diabetes Study Group. Diabetes 1995; 44: 1249–58.
    3. Maedler K, Spinas GA, Dyntar D et al. Diabetes 2001; 50: 69–76.
    4. Paolisso G, Howard BV. Diabet Med 1998; 15: 360–66.
    5. Jones NP, Charbonnel B, Lönnqvist F et al. Diabetologia 1999; 42(suppl 1): A229, Abs 859 and
  • This analysis from the Heart Outcomes Protection Evaluation (HOPE) study evaluated the effects of abdominal obesity (tertiles of waist circumference) on the risk of all-cause or cardiovascular death, or MI in 6,620 men and 2,182 women followed for an average of 4.5 years. Results were adjusted for BMI, age, smoking, sex, previous MI, stroke, peripheral arterial disease, microalbuminuria, use of antiplatelet agents, diuretics, lipid-lowering agents, and anti-hypertensives, history of hypertension, diabetes, or total cholesterol >5.2 mmol/L, or HDL-cholesterol <0.9 mmol/L.
    The risk of cardiovascular death, MI, or death from any cause increased in line with increasing tertiles of waist circumference. These data from this major intervention study add to the growing database of evidence linking high waist circumference with a clinically significant increase in the risk of an adverse cardiovascular outcome.
  • These data are from the Nurses’ Health Study (Carey VJ et al, 1997), an observational study that followed a cohort of 43,581 women between 1986 and 1994 in the USA. The analysis presented here was designed to define the association between waist circumference and the risk of developing type 2 diabetes.
    The risk of developing type 2 diabetes increased linearly with an increasing waist circumference. The relative risk for women at the 90th percentile of waist circumference (equivalent to a waist measurement of 92 cm [36 in]) was 5.1 (95% CI 2.98.9) compared with women at the 10th percentile (waist measurement of 67 cm [26.2 in]). High waist circumference is a powerful predictor of an increased risk of developing type 2 diabetes (Wang Y et al, 2005).
  • The prospective Nurses Health Study set out to assess the impact of factors such as waist circumference in determining risk of CHD in a cohort of 44,702 US female registered nurses, aged 40 to 65 years, recruited between 1986 and 1994. Study subjects were free of prior CHD at baseline.
    During 8 years of follow-up, there was a direct, independent and continuous relationship between waist circumference and age-adjusted risk of CHD.
  • We have understood for decades the roles of ‘classical’ risk factors – elevated LDL-cholesterol, hypertension, elevated blood glucose and smoking – in the pathogenesis of cardiovascular disease. More recent research is continuing to define the contribution of emerging risk factors to the risk of developing type 2 diabetes and cardiovascular disease, particularly in the setting of insulin resistance. Abdominal obesity is associated with multiple cardiometabolic risk factors such as atherogenic elevated blood glucose (hypertriglyceridaemia and low HDL-cholesterol), elevated blood glucose and inflammation, which are major drivers of cardiovascular disease and type 2 diabetes. In addition, atherosclerosis is increasingly regarded as an inflammatory condition.
  • Public education is key!
    Recognizing risk factors and dealing with them is important,
    Recognizing clusters of risk factors is important, i.e, when some of the factors are recognized others should be investigated.
    Using the correct drugs to treat the various risk factors is important.
    ACEI or ARB
    TZD’s or Glitazars
    Statins with or without fibric acid derivatives
    Treating to goal.
    Smoking cessation.
  • Public education is key!
    Recognizing risk factors and dealing with them is important,
    Recognizing clusters of risk factors is important, i.e, when some of the factors are recognized others should be investigated.
    Using the correct drugs to treat the various risk factors is important.
    ACEI or ARB
    TZD’s or Glitazars
    Statins with or without fibric acid derivatives
    Treating to goal.
    Smoking cessation.
  • Public education is key!
    Recognizing risk factors and dealing with them is important,
    Recognizing clusters of risk factors is important, i.e, when some of the factors are recognized others should be investigated.
    Using the correct drugs to treat the various risk factors is important.
    ACEI or ARB
    TZD’s or Glitazars
    Statins with or without fibric acid derivatives
    Treating to goal.
    Smoking cessation.
  • Section VI, “Prevention and Management of Diabetes Complications,” includes 48 slides(1 slide unless otherwise noted):
    Cardiovascular Disease (CVD) in Individuals with Diabetes
    Recommendations: Hypertension/Blood Pressure Control (8 slides)
    Recommendations: Dyslipidemia/Lipid Management (7 slides)
    Secondary Prevention: Reduction in 10-Year Risk of Major CVD Endpoints
    Primary Prevention: Reduction in 10-Year Risk of Major CVD Endpoints
    Recommendations: Glycemic, Blood Pressure, Lipid Control in Adults
    Recommendations: Antiplatelet Agents (3 slides)
    Recommendations: Smoking Cessation
    Recommendations: Coronary Heart Disease Screening
    Recommendations: Coronary Heart Disease Treatment (2 slides)
    Recommendations: Nephropathy
    Recommendations: Nephropathy Screening
    Recommendations: Nephropathy Treatment (5 slides)
    Definitions of Abnormalities in Albumin Excretion
    Stages of Chronic Kidney Disease
    Management of CKD in Diabetes
    Recommendations: Retinopathy
    Recommendations: Retinopathy Screening (4 slides)
    Recommendations: Retinopathy Treatment (2 slides)
    Recommendations: Neuropathy Screening/Treatment (2 slides)
    Recommendations: Neuropathy Foot Care (4 slides)
  • Type 2 diabetes is a progressive disease and lifestyle adjustments alone are rarely sufficient in the long term – almost all patients will eventually require drug treatment to control their glucose levels.1
    1.Turner RC et al. JAMA 1999; 281: 2005–2012.
  • Carroll S, Dudfield M. Wath is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Sports Med 2004; 34(6):371-418
    Park HS, Lee K. Diabet Med 2005
    Busetto L. Nutr Metab Cardiovascular Dis 2001
  • Clinical guidelines. National Institute of Health.
    Website: http: //
  • “Standards of Medical Care in Diabetes—2011” contains all of the current and key clinical recommendations of the American Diabetes Association (ADA)
    These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care
    While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided
    These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed
    The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to affect health outcomes of patients with diabetes favorably
    The slides are organized to correspond with sections within the “Standards of Medical Care in Diabetes—2011”
    While not every section in the document is represented, these slides do incorporate the most salient points from the Position Statement
    These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence; subsequently, they are reviewed and approved by the Executive Committee of ADA’s Board of Directors
  • The American Diabetes Association has developed a grading system for clinical recommendations (Table 1)
    This grading system was used to clarify and codify evidence that forms the basis for each of the recommendations in the “Standards of Medical Care in Diabetes—2011”
    The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E
    This slide summarizes the description for each of these levels of evidence
  • This slide represents a summary of recommendations for glycemic, blood pressure, and lipid control for most adults with diabetes
  • Diagnostic criteria from ATP III, WHO and IDF vary enough that different segments of populations are identified as having MS .
    Emphasizes the need to treat individually all components of the syndrome.
    It is still important to recognize that clustering of CVD risk factor does occur and to be astute in looking for and addressing all the factors.
    As more research is done the underlying common biochemical denominators are being identified and medications are being developed that address the root causes of the various components of the syndrome.
  • Metabolic syndrome november 2014

    2. 2. PBRC 2005 What Are the Potential BenefitsWhat Are the Potential Benefits of Personalized Medicine?of Personalized Medicine?  Earlier disease protection  Optimize therapeutic selection and dosing  Reduce adverse drug reactions  Increase patient compliance with therapy  Reduce the time, cost, and failure rate of clinical trials by  improving the selection of targets for drug discovery  “Save” therapeutics  Shift the emphasis in medicine from reaction to prevention  Reduce the overall cost of healthcare
    3. 3. PBRC 2005 Tools Needed for Prediction and Personalized CareDiseaseBurden Time Cost 1/reversibility Typical Current Intervention Earliest Clinical Detection Earliest Molecular Detection Initiating Events Baseline Risk Decision Support Tools: Baseline Risk Preclinical Progression Disease Initiation and Progression Assess Risk Refine Assessment Predict/Diagnose Monitor Progression Predict Events Inform Therapeutics Sources of New Biomarkers: Stable Genomics: Single Nucleotide Polymorphisms (SNPs) Haplotype Mapping Gene Sequencing Dynamic Genomics: Gene Expression Proteomics Therapeutic Decision Support
    4. 4. PBRC 2005 Macrovascular complications
    5. 5. PBRC 2005
    7. 7. Why accelerated NO Definite Answers Many factors Risk factors
    8. 8. Is it preventable or at least delayed yes
    9. 9. Atherosclerosis: An Inflammatory Disease III.2 © 2002 PPS® C
    10. 10. PBRC 2005 1. Atherosclerotic lesions Fatty streaks. Gelatinous plaques. Fibrous plaques. Complicated plaques. 2. Theories of atherogenesis Lipid hypothesis. Thrombogenetic hypothesis. Mesenchymal hypothesis. Monoclonal hypothesis. Response to injury hypothesis.
    11. 11. PBRC 2005 C – Peptide and atherosclerosis   C-peptide protects endothelial cells from apoptosis and inflammation triggered by high glucose conditions [62]. The situation can be totally different in patients with insulin resistance and type 2 diabetes where high levels of C-peptide could have opposite effects.
    12. 12. PBRC 2005 Cardiometabolic Risk Global Diabetes / CVD Risk Overweight / Obesity Inflammation Hypercoagulation Elevated Blood Pressure Smoking Age, Race, Sex, Family History ↑Glucose↑BP↑ Lipids Age Genetics Insulin Resistance Abnormal Lipid Metabolism. LDL ↑ or ↑ ApoB HDL ↓ Triglycerides ↑
    13. 13. PBRC 2005 Prevalence of MeS in different Countries Country Year Sample Prevalenc e (%) Arab Americans 2003 542 23 Oman 2001 1419 21 Jordan 2002 1121 36 Saudi Arabia 2004 2250 20.8 Palestine 1998 17* Qatar 2007 817 27.6 Turkey 2004 1637 33.4* Iran ? 10368 33.7 * Crude rates Mussallam et al. Int J Food Safety and PH 2008
    14. 14. PBRC 2005
    15. 15. PBRC 2005
    16. 16. PBRC 2005 What are the clinical outcomes of the metabolic syndrome? Cardiovascular disease  Relative risk = 2x Type 2 diabetes  Relative risk = 5x  Fatty liver  Obstructive sleep apnea  Cholesterol gallstone  Polycystic ovarian disease
    17. 17. PBRC 2005 Definitions of the Metabolic Syndrome  We get a new definition about every 2 years  We now have 7 definitions  No definition has been accompanied by data on its sensitivity, specificity and positive predictive value
    18. 18. PBRC 2005 Metabolic Syndrome: Overview  Metabolic Syndrome is not a disease, but rather a cluster of disorders of your body’s metabolism, including: o High blood pressure o High insulin levels o Excess body weight o Abnormal cholesterol levels  Each of these disorders is by itself a risk factor for other diseases.  In combination, however, these disorders dramatically boost the chances of developing potentially life-threatening illnesses, such as diabetes, heart disease or stroke.
    19. 19. PBRC 2005 What are unresolved questions about the MetS? (Kahn et al. 2005)  Metabolic syndrome name?  Existence of metabolic syndrome?  More than some of its parts?  MetS vs. prediabetes & type 2 diabetes  Diagnostic utility?  Pathogenesis?  Clinical utility?
    20. 20. PBRC 2005 Is the metabolic syndrome a “syndrome”?  A collection of things  Clustering of signs and symptoms  Three or more related entities
    21. 21. PBRC 2005  Plurametabolic syndrome (Crepaldi)  Syndrome X (Reaven)  Deadly Quartet (Kaplan)  Metabolic syndrome (WHO; NCEP: IDF)  Insulin resistance syndrome (EGIR; AACE)  Dysmetabolic syndrome  Cardiometabolic syndrome  CHAOS (Australia) What should the metabolic syndrome be called?
    22. 22. PBRC 2005 What is the metabolic syndrome? Clustering of Metabolic Risk Factors (3+)  Atherogenic dyslipidemia  Elevated blood pressure  Elevated plasma glucose  Prothrombotic state  Proinflammatory state
    23. 23. PBRC 2005 Diagnosing Metabolic Syndrome  Waist Circumference o Greater than 35 inches in women and 40 inches in men (abdominal obesity)  Triglyceride o Levels of 150 milligrams per deciliter (mg/dl) or higher  Blood Pressure o 130/85 millimeters of mercury or higher  Fasting blood glucose o Level of 110 mg/dl or higher  High-density lipoprotein cholesterol (HDL) o Lower than 50 mg/dl in women and 40 mg/dl for men According to the National Cholesterol Education Program (NCEP), the presence of three or more of the following traits indicates metabolic syndrome:
    24. 24. PBRC 2005 ATP III Clinical Identification of the Metabolic Syndrome  Waist circumference:  Men>102 cm (>40 in)  Women>88 cm (>35 in)  Triglycerides >150 mg/dL  HDL cholesterol:  Men<40 mg/dL  Women<50 mg/dL  Blood pressure 130/ 85 mm Hg  Fasting glucose >110 mg/dL* * New ADA guidelines suggest >100mg/dl increases risk for Metabolic Syndrome
    25. 25. PBRC 2005 International Diabetes Federation (IDF) Definition  Modified ATPIII definition  Fasting Glucose > 100mg/dl  Adjusted waist circumference based on ethnicity (i.e. asians with lower waist circumference threshold than pacific islanders)
    26. 26. PBRC 2005 Clinical Measure WHO (1998) AACE (2003) AHA/NHLBI (2005) IDF (2005) Insulin resistance IGT, IFG, T2DM, or ins. resist. And 2 of the below IGT or IFG. And any of the below. Clinical judgment None. 3 of the below None Obesity WHR >0.90 in men or >0.85 in women and/or BMI >30 BMI > 25 Waist ≥102 cm in men or ≥88 cm in women Waist (population specific). And any 2 of the below TG (mg/dl) TG >150 and/or HDL-C <35 in men or < 39 in women TG >150 and HDL-C <40 in men or <50 in women ≥150 or Rx ≥150 or Rx HDL (mg/dl) <40 in men, <50 in women or Rx <40 in men, <50 in women or Rx Blood pressure (mm Hg) >140/90 > 130/85 mm Hg ≥130 or ≥85 or Rx ≥130 or ≥85 or Rx Glucose (mg/dl) IGT, IFG, or T2DM IGT or IFG (not diabetes) > 100 or Rx > 100 or Rx Other Microalbuminuria Other features of insulin resistance
    27. 27. PBRC 2005 References  Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). (2)Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.  International Diabetes Federation  Insulin-sensitising drugs, The Cochrane Database of Systematic Reviews Date of last Substantial Update: December 31. 2002  Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia, NEJM. Nov 2005
    28. 28. PBRC 2005 Insulin-resistance andInsulin-resistance and ββ-cell function-cell function Amiloyd storeAmiloyd store GlucotoxicityGlucotoxicity (hyperglycemia(hyperglycemia)) Hyper-Hyper- insulinaemiainsulinaemia ProteinProtein GlycosilationGlycosilation LipotoxicityLipotoxicity ((↑↑ FFA e TG)FFA e TG) Insulin-Insulin- resistanceresistance ⇩⇩ ββ-cell-cell functionfunction
    29. 29. PBRC 2005 The new IDF definition focusses on abdominal obesity rather than insulin resistance International Diabetes Federation (IDF) Consensus Definition 2005
    30. 30. PBRC 2005 Fat Topography In Type 2 Diabetic Subjects Intramuscular Intrahepatic Subcutaneous Intra- abdominal FFA* TNF-alpha* Leptin* IL-6 (CRP)* Tissue Factor* PAI-1* Angiotensinogen*
    31. 31. PBRC 2005 NEFA  Cytokines (TNFα & IL-6) Adiponectin  PAI-1  Leptin  Resistin  Angioten- sinogen Adipos e Tissue Adipos e Tissue Metabolic Risk Factors Elevated Blood Pressure Atherogenic Dyslipidemia Elevated Glucose Pro- thrombotic State Pro- inflammatory State How does obesity contribute to MetS?
    32. 32. PBRC 2005 Diabetes Obesity Dia Besity Diabesity Up–regulation of adiponectin and its receptor, through the use of thiazolidinediones, has been found to be partially related to insulin sensitization and thus antidiabetic effects.
    33. 33. PBRC 2005 Abdominal obesity and increased risk of cardiovascular events Dagenais GR et al, 2005 Adjustedrelativerisk 1 1 1 1.17 1.16 1.14 1.29 1.27 1.35 0.8 1 1.2 1.4 CVD death MI All-cause deaths Tertile 1 Tertile 2 Tertile 3 Men Women <95 95–103 >103 <87 87–98 >98 Waist circumference (cm): The HOPE study Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C; CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index; DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol
    34. 34. PBRC 2005 Abdominal obesity increases the risk of developing type 2 diabetes <71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3 24 20 16 12 8 4 0 Relativerisk Waist circumference (cm) Carey VJ et al, 1997
    35. 35. PBRC 2005 Abdominal obesity is linked to an increased risk of coronary heart disease Waist circumference has been shown to be independently associated with increased age-adjusted risk of CHD, even after adjusting for BMI and other cardiovascular risk factors 0.0 0.5 1.0 1.5 2.0 2.5 3.0 <69.8 69.8−<74.2 74.2−<79.2 79.2−<86.3 86.3−<139.7 1.27 2.06 2.31 2.44p for trend = 0.007 Relativerisk Quintiles of waist circumference (cm) Rexrode KM et al, 1998 CHD: coronary heart disease; BMI: body mass index
    37. 37. PBRC 2005 MS Excel Program for Risk Assessment From The Framingham Heart Study Enter Values Here CHD(MI and Coronary Death) Risk Prediction National Cholesterol Education Program Adult Treatment Panel III Risk Factor Units (Type Over Placeholder Values in Each Cell) Notes Gender male (m) or female (f) M Age years 52 Total Cholesterol mg/dL 220 HDL mg/dL 45 Systolic Blood Pressure mmHg 146 Treatment for Hypertension {Only if SBP>120} yes (y) or no (n) N Current Smoker yes (y) or no (n) Y Time Frame for Risk Estimate 10 years 10 Your Risk (The risk score shown is derived on the basis of an equation. Other NCEP materials, such as ATP III print products, use a point-based system to calculate a risk score that approximates the equation-based one.) 0.17 17% Tab If value is < the minimum for the field, enter the minimum value. If value is > the maximum for the field, enter the maximum value. These functions and programs were prepared by Ralph B. D'Agostino, Sr., Ph.D. and Lisa M. Sullivan, Ph.D., Boston University and The Framingham Heart Study and Daniel Levy, M.D., Framingham Heart Study, National Heart, Lung and Blood Institute. 0.17 0.04 0.02 0.00 0.05 0.10 0.15 0.20 0.25 0.30 Your Risk Estimate, Comparative Risks for Lowest = Total Chol<160, HDL>60, Optimal SBP (<120), No Trt for Htn, Non-Smoker Same Age and Gender Low = Total Chol 160-199, HDL 50-59, Normal SBP (<130), No Trt for Htn, Non-Smoker
    38. 38. PBRC 2005 TargetingTargeting Cardiometabolic RiskCardiometabolic Risk
    39. 39. PBRC 2005 Six Aims for Improvement  Safe – avoiding injuries to patients from the care that is intended to help them.  Effective – providing services based on scientific knowledge to all who could benefit and refraining from providing services to those not likely to benefit (avoiding underuse and overuse)  Patient-centered – providing care that is respectful of and responsive to individual patient preferences, needs and values and ensuring that patients values guide all clinical decisions.  Timely – reducing waits and sometimes harmful delays for both those who receive and those who give care.  Efficient – avoiding waste, including waste of equipment, supplies, ideas and energy.  Equitable – providing care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographic location, and socio-economic status.
    40. 40. PBRC 2005 Global cardiometabolic risk* Gelfand EV et al, 2006; Vasudevan AR et al, 2005 * working definition
    41. 41. PBRC 2005 Intensive therapyIntensive therapy AggressiveAggressive TTOTTO Maximum TherapMaximum Therap dosedose
    42. 42. PBRC 2005 Public HealthPublic Health ApprachApprach
    43. 43. PBRC 2005 Diabetes prevention
    44. 44. PBRC 2005  Public Education  Screening for at risk individuals:  Blood Sugar/ HbA1c  Lipids  Blood pressure  Tobacco use  Body habitus  Family history Screening/Public Health ApproachScreening/Public Health Approach
    45. 45. PBRC 2005 Prevention of type 2 diabetes Before people develop type 2 diabetes, they almost always have "pre-diabetes" -- blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes Take our diabetes risk test to see if you are at risk for developing diabetes. Diabetes is more common in African Americans, Latinos, Native Americans, Asian Americans and Pacific Islanders. is a powerful new risk assessment tool. It can be used to explore the effects of a wide variety of health care interventions, including losing weight, stopping smoking, and taking certain medications. Diabetes Prevention Program study conclusively showed that people with pre-diabetes can prevent the development of type 2 diabetes by making changes in their diet and increasing their level of physical activity. Keeping an eye on these risk factors -- keeping them "in check" -- can help you prevent diabetes and heart disease. Keeping an eye on these risk factors -- keeping them "in check" -- can help you prevent diabetes and heart disease.
    47. 47. PBRC 2005 Lifestyle modification  Diet  Exercise  Weight loss  Smoking cessation If a 1% reduction in HbA1c is achieved, you could expect a reduction in risk of: • 21% for any diabetes-related endpoint • 37% for microvascular complications • 14% for myocardial infarction However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis Stratton IM et al. BMJ 2000; 321: 405–412.
    50. 50. PBRC 2005 Weight loss may be obtainedWeight loss may be obtained through:through: • Therapeutic lifestyle changeTherapeutic lifestyle change • Drug therapyDrug therapy (if Therapeutic lifestyle change is not sufficient)(if Therapeutic lifestyle change is not sufficient) • Bariatric surgeryBariatric surgery (in selected cases; to estimate the risk/benefit ratio)(in selected cases; to estimate the risk/benefit ratio)
    51. 51. PBRC 2005 ↓↓ glycemia ed insulinaemiaglycemia ed insulinaemia ↓↓ HbAHbA1C1C ↓↓ VLDL and triglyceridesVLDL and triglycerides ↑↑ HDL-cholesterolHDL-cholesterol ↓↓ blood pressureblood pressure ↓↓ microalbuminuriamicroalbuminuria .. EFFECTIVE LONG TERM WEIGHT LOSS:EFFECTIVE LONG TERM WEIGHT LOSS: ACHIEVABLE OBJECTIVES and HEALTH BENEFITSACHIEVABLE OBJECTIVES and HEALTH BENEFITS
    53. 53. PBRC 2005 ADA Evidence Grading System for ClinicalADA Evidence Grading System for Clinical RecommendationsRecommendations Level ofLevel of EvidenceEvidence DescriptionDescription A Clear or supportive evidence from adequately powered well-conducted, generalizable, randomized controlled trials Compelling nonexperimental evidence B Supportive evidence from well-conducted cohort studies or case-control study C Supportive evidence from poorly controlled or uncontrolled studies Conflicting evidence with the weight of evidence supporting the recommendation E Expert consensus or clinical experience ADA. Diabetes Care 2011;34(suppl 1):S12. Table 1.
    54. 54. PBRC 2005 Recommendations: Glycemic, Blood Pressure,Recommendations: Glycemic, Blood Pressure, Lipid Control in AdultsLipid Control in Adults A1C <7.0%* 6.5 Blood pressure <130/80 mmHg† Lipids LDL cholesterol <100 mg/dl (<2.6 mmol/l)‡ *More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on: duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient considerations. †Based on patient characteristics and response to therapy, higher or lower systolic blood pressure targets may be appropriate. ‡In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l), using a high dose of statin, is an option. ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31. Table 12.
    55. 55. PBRC 2005 J Am Coll Cardiol. 2012;60(14):1231- 1238. doi:10.1016/j.jacc.2012.05.019  Clinical Research | October 2012  Statins, Risk of Diabetes, and Implications on Outcomes in the General Population  Kang-Ling Wang, MD; Chia-Je  Conclusions Risk of diabetes was increased after statins, but outcomes were favorable.
    56. 56. PBRC 2005 Diabetes. 2012 Feb;61(2):463-73.  Silence of TRIB3 suppresses atherosclerosis and stabilizes plaques in diabetic ApoE-/-/LDL receptor-/- mice.  Toll-like receptor (TLR)4 TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic apoE-/- mice and lowered serum cholesterol and triglyceride levels in non- diabetic apoE-/- mice.
    57. 57. PBRC 2005 A Critical Look at theA Critical Look at the Metabolic SyndromeMetabolic Syndrome Is it a Syndrome?*Is it a Syndrome?*  “…too much clinically important information is missing to warrant its designations as a syndrome.”  Unclear pathogenesis, Insulin resistance is not a consistent finding in some definitions.  CVD risks has not shown to be greater than the sum of it’s individual components. *ADA
    58. 58. PBRC 2005 A Critical Look at theA Critical Look at the Metabolic SyndromeMetabolic Syndrome
    59. 59. PBRC 2005