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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

Diabetes Mellitus 101 for Cardiologists (and Alike): 2015. An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: The Role of Anti-Diabetes Medications in Reducing CV Risk and Outcomes in Patients with Diabetes:

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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

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  1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: The Role of Anti-Diabetes Medications in Reducing CV Risk and Outcomes in Patients with Diabetes: Diabetes Medications May be a Cardiologist’s Best Friend Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000

  2. Natural History of ALLDM Age 0-15 15-40+ 15-50+ 25-70+ Macrovascular Complications Disability IR Phenotype MICVAAmp IGT ALL DM DEATH BlindnessAmputationCRF EyeNerveKidney ETOHBPSmoking Disability Microvascular Complications Risk of Dev. Complications

  3. Type2 diabetesisincreasinglyprevalent • Globally, 387 million people • • are living with diabetes1 At least 68% of people >65 years with diabetes die of heart disease2 Mortality risk associated with diabetes(n=820,900)3 3 Hazardratio(95%CI) (diabetesvsnodiabetes) 2 1 0 This will rise to 592 million by 20351 All-cause mortality CVdeath 1. IDF Diabetes Atlas 6th Edition 2014 http://www.idf.org/diabetesatlas; 2. Centers for Disease Control and Prevention 2011; 3. Seshasai et al. N Engl J Med 2011;364:829-41

  4. Hyperglycemia Leads to Complications: May Be Present Prior to Diagnosis Hyperglycemia Spike (+variability) Argument for Early Discovery Pre-diabetes, Early Treatment, Determine on Hospital Admission Continuous PPG A1C Chronic toxicity Acute toxicity Tissue lesion Diabetic complications Microvascular Macrovascular Nephropathy MI Stroke Retinopathy Neuropathy PVD American Diabetes Association. At: http://www.diabetes.org/diabetes-statistics/complications.jsp. Brownlee M. Diabetes mellitus: theory and practice. Elsevier Science Publishing Co., Inc; 1990:279-291. Ceriello A. Diabetes. 2005;54:1-7. 4

  5. Diabetes is associated with significant loss of life years Men Women 7 7 Non-vascular deaths Vascular deaths 6 6 Starts with inc. PPG 5 5 Yearsof lifelost 4 4 3 3 2 2 1 1 0 0 040 50 60 70 Age (years) 80 90 040 50 60 70 Age (years) 80 90 On average, a 50-year-old individual with diabetes and no history of vascular disease will die 6 years earlier compared to someone without diabetes . Seshasaiet al. N EnglJ Med2011;364:829-41

  6. Cardiovascular disease and diabetes No A1C threshold is apparent Finnish study by Kuusisto et al; UKPDS epidemiologic analysis; EPIC-Norfolk Study ~65% of deaths are due to CV disease Cardiovascular complications of T2DM Coronary heart disease deaths2- to 4-fold Stroke risk 2- to 4-fold Impaired glucose tolerance (IGT) and postprandial hyperglycemia are CV risk factors Funagata Diabetes Study; Honolulu Heart Program; DECODE Study; Rancho Bernardo Study Heart failure 2- to 5-fold Bell DSH. Diabetes Care. 2003;26:2433-41. Centers for Disease Control (CDC). www.cdc.gov. T2DM = type 2 diabetes mellitus

  7. Early Treatment Decreases Micro and Macro Vascular RISK

  8. Impact of Intensive Therapy in Type 2 Diabetes Summary of Major Clinical Trials: BUT Subset Evaluations Show Reduced CV Outcomes if shorter duration of DM, without significant pre-existing complications Initial Trial Long Term Follow-up ↑- likely due to hypoglycemia and weight gain

  9. Meta-analysis of intensive glucose control in T2DM: major CV events including heart failure Numberofevents More intensive Less intensive Differencein HR(95%CI) HbA1c(%) -0.88 0.96 (0.83,1.10) Stroke 378 370 Myocardialinfarction 730 745 -0.88 0.85 (0.76,0.94) Hospitalisation for or death from heart failure 459 446 -0.88 1.00 (0.86,1.16) 0,50 1,00 2,00 Favoursmoreintensive Favourslessintensive • Meta-analysis of 27,049 participants and 2370 major vascular events from: – – – – ADVANCE UKPDS ACCORD VADT HR, hazard ratio; CV, cardiovascular Turnbull FM et al. Diabetologia 2009;52:2288–2298

  10. But Why was there an apparent increase in Mortality in ACCORD, lack of benefit in ADVANCE • Weight Gain • Hypoglycemia • ACCORD • recorded PRIOR history mild severe events- • NO DOCUMENTATION OF GLUCOSE AT TIME OF DEATH

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