Therapy of Type 2 Diabetes Mellitus: UPDATE Glycemic Goals in the Care of Patients with Type 2 Diabetes ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM) Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System Clinical Associate Professor of Medicine, Emeritus, U of Pa

Duggal, Evidence-Based Medicine in Practice,, Int’l j. Clinical Practice,65: ,2011 Sniderman, A. et al. The Necessity for Clinical Reasoning in the Era of Evidence-based Medicine, Mayo Clinic Proceedings, 2013, 8:1108 Lecture Based on Evidence -Based PRACTICE EBM=Evidence Based Medicine Has Led to Students/MDs who don’t Think- Eg: if no evidence, continue doing same old dangerous therapy (SU); Specialists are abrogating their responsibility to evaluate and lead in use of new medications, processes of care = Evidence Based Practice EBM=Evidence Based Medicine Research Evidence Randomized, Prospective Publication Trials Critical Appraisal Patient-Based Experience Clinical expertise Expert Opinions Guidelines + +

Natural History of Type 2 Diabetes IR phenotype Atherosclerosis obesity hypertension  HDL,  TG, HYPERINSULINEMIA Endothelial dysfunction PCO,ED Envir.+ Other Disease Obesity (visceral) Poor Diet Inactivity Insulin Resistance Risk of Dev. Complications ETOH BP Smoking Eye Nerve Kidney  Beta Cell Secretion Genes Blindness Amputation CRF Disability MI CVA Amp Age Macrovascular Complications IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia Microvascular Complications DEATH pp>7.8

‘Ominous Octect: Pathophysiological Contributions to Hyperglycemia in Type 2 Diabetes 5.Gut carbohydrate absorption Peripheral glucose uptake Hepatic glucose production Pancreatic insulin secretion 2.Pancreatic glucagon secretion HYPERGLYCEMIA 6.Fat- increased lipolysis, inc FFA 7.Brain- Inc. Appetite Insulin Resistance, Decrease, GLP-1 8.Kidney- 3.Muscle 4.Liver

Natural History of Type 2 Diabetes IR phenotype Atherosclerosis obesity hypertension  HDL,  TG, HYPERINSULINEMIA Endothelial dysfunction PCO,ED Envir.+ Other Disease Obesity (visceral) Poor Diet Inactivity Insulin Resistance Risk of Dev. Complications ETOH BP Smoking Eye Nerve Kidney  Beta Cell Secretion Genes Blindness Amputation CRF Disability MI CVA Amp Age Macrovascular Complications IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia Microvascular Complications DEATH pp>7.8

Why Bother to Treat Agressively?

One third of adults with diabetes are undiagnosed  ~10% of US adults have diabetes/~20 million persons in 2005  Nearly one third don’t know they have diabetes  26% of US adults have impaired fasting glucose (IFG)* *100–125 mg/dL Cowie CC et al. Diabetes Care. 2006;29: NIDDK. National Diabetes Statistics. Total: 35% of US adults with diabetes or IFG ~73.3 million persons SCREEN/ IDENTIFY

9 Hyperglycemia Spike PPG Continuous A1C Acute toxicity Chronic toxicity Tissue lesion Diabetic complications Microvascular Macrovascular RetinopathyNephropathyNeuropathyPVD MIStroke American Diabetes Association. At: Brownlee M. Diabetes mellitus: theory and practice. Elsevier Science Publishing Co., Inc; 1990: Ceriello A. Diabetes. 2005;54:1-7. Hyperglycemia Leads to Complications

Each of the increments of mean glucose level is subdivided into four quartiles of glycemic variability. Q1 represents the lowest quartile; Q4 represents the highest quartile Glucose Variability as a predictor of mortality within different ranges of mean glucose Higher sugars/ higher Variability Higher the Mortality Hermanides, Critical Care Med,38:838, 2010

FBS>126 Ppg>200 New Hyperglycemia #223 (12%) Known Diabetes #495 (26%) Normo- Glycemia #1168 Mortality, total Mortality, ICU Mortality, non-ICU LOS ICU Admission D/c Dispo. Home Transition Care Nursing Home RISK OF UNRECOGNIZED HYPERGYCEMIA: Effect of Hyperglycemia on Mortality, LOS, ICU admission, D/C Disposition Umpierrez, JCEM 2002;87:978