1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: Looking at Diabetes Medications with a Cardiologists Eye Part 4

2. CV Risk of SU and Insulin Pharmacoepidemiology and Drug Safety. 2008;(17):753-759. So benefit of both SU/Insulin in research studies –UKPDS, DCCT/EDIC But adverse risk in ‘real world’ use

3. So given epidemiologic data, CV risk/glucose data and now ADVANCE, VADT, ACCORD, implications of weight gain and hypogycemia, what are/ should be goals (SSS) 1. ADA- stayed at <7.0 AACE – stayed at < 6.5 Lowest possible as long as no undue risk of hypoglycemia and visceral weight gain 2. ADA and AACE- a.Start early in DM - implications for prevention- lifestyle and drug therapy of metabolic syndrome and IGT b. do not aim for aggressive control in those with significant pre-existing CV disease Disagree- lowest possible without hypoglycemia, weight gain 3.Modify goals for ‘elderly’ Disagree- lowest possible without hypoglycemia, weight gain

4. Intensive treatment/ standard treatment Weight of study size Odds ratio (95% CI) ParticipantsEvents UKPDS3071/1549426/2598.6%0.75 (0.54–1.04) PROactive*2605/2633164/20220.2%0.81 (0.65–1.00) ADVANCE5571/5569310/33736.5%0.92 (0.78–1.07) VADT892/89977/909.0%0.85 (0.62–1.17) ACCORD5128/5123205/24825.7%0.82 (0.68–0.99) Overall17267/157731182/1136100%0.85 (0.77–0.93) 0.40.60.81.01.21.41.61.8 Intensive treatment betterStandard treatment better *Included on-fatal MI and death from all-cardiac mortality Probability of events of CAD with intensive glucose-lowering vs. standard treatment 2.0 Intensive treatment/ standard treatment Weight of study size Odds ratio (95% CI) ParticipantsEvents UKPDS3071/1549221/14121.8%0.78 (0.62–0.98) PROactive*2605/2633119/14418.0%0.83 (0.64–1.06) ADVANCE5571/5569153/15621.9%0.98 (0.78–1. 23) VADT892/89964/789.4%0.81 (0.58–1.15) ACCORD5128/5123186/23528.9%0.78 (0.64–0.95) Overall17267/15773743/754100%0.83 (0.75–0.93) Intensive treatment betterStandard treatment better Probability of events of non-fatal MI with intensive glucose-lowering vs. standard treatment www.thelancet.com. Vol 373 May 23, 2009. Lancet Meta-analysis 0.40.60.81.01.21.41.61.82.0 0.9% Dec. HbA 1c, 17% Dec. non-fatal MI, 15% Dec. CV events of CAD

5. Trends in Age-Standardized Rates of Diabetes-Related Complications among U.S. Adults with and without Diagnosed Diabetes, 1990–2010. Gregg EW et al. N Engl J Med 2014;370:1514-1523

8. Perioperative Glycemic Control: Improves Mortality  Portland Diabetic Project: Furnary, et al. ’87-’91: SQI (< 200 mg/dL) ’91-’98: CII (150-200 mg/dL) ’99-’01: CII (125-175 mg/dL) ’01  : CII (100-150 mg/dL) Post Intra + Post

10. VALUE OF CONTROLLING HYPERGLYCEMIA IN HOSPITAL

11. RISK OF TOO TIGHT CONTROL OF HYPERGLYCEMIA IN HOSPITALS