1. 1 Part 1 Importance of Identifying and Managing Postprandial Hyperglycemia An Educational Service from G LYCO M ARK G LYCO M ARK is a registered trademark of GlycoMark, Inc. © GlycoMark, Inc. All rights reserved NOTE: Please see slide notes below each page for study and slide details

2. 2 4 Part Series - Identifying and Managing Postprandial Hyperglycemia (PPH) 1.Importance of identifying and managing postprandial hyperglycemia (PPH) 2.Routinely identifying PPH – challenges and tools 3.Interpretation and clinical use of a new biomarker for PPH 1,5-Anhydroglucitol 4.1,5-Anhydroglucitol outcomes research

3. 3 The Glycemic Triad 1 Postprandial Hyperglycemia 60-90 day mean glucose Fasting Glucose Baseline/preprandial glucose HbA1C ADA: <7.0% AACE: <6.5% ADA: <180 mg/dL AACE: <140 mg/dL ADA: 70-130 mg/dL AACE: <110 mg/dL Nearly 40% of patients in “good control” have significant glucose variability 2 1 Monnier et al. Current Diabetes Reports 2008, 8:368–374 2 Bonora et al. Diabetologia, 2006

4. 4 Attaining A1C below 7% is difficult but important DCCT and UKPDS demonstrated every 1% reduction in A1C significantly reduces complications Postmeal glucoses often not available for safe adjustment of fasting vs. prandial medications in patients with similar A1Cs Postprandial hyperglycemia (PPH) has been proven to independently contribute to diabetes complications 1-9 1 Gimeno-Orna J, Castro-Alonso F, Boned-Juliani B, Lou-Arnal L. Fasting plasma glucose variability as a risk factor of retinopathy in Type 2 diabetic patients. J Diabetes Complications. 2003;17(2):78-81 2 DCCT Research Group. N Engl J Med. 1993;329:977-986 3 DCCT Research Group, The relationship of glycemic exposure (HbA1C) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968-83 4 DECODE Study Group. Lancet 1999; 354:617–621 5 Hanefeld M, et al., for the DIS Group. Riskfactors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up.Diabetologia 1996;39:1577-83 6 Gerich J., Clinical Significance, Pathogenesis and Management of Postprandial Hyperglycemia, Arch Intern Med 2003; 163:1306-1316 7 Esposito K. Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in T2DM,Circulation, 2004;110;214-2198 8 Cavalot, et al. Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose inType 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study, Clin Endocrinol Metab 91: 813–819,2006 9 Emoto, et al. Effect of 3-Month Repeated Administration of Miglitol on Vascular Endothelial Function in Patients With Diabetes Mellitus and Coronary Artery Disease, J Cardiol 2011

5. 5 Postprandial Hyperglycemia and Coronary Artery Disease Reduction in Coronary Lumen Diameter with each PPG increase Mellen PB et al. Poster Presentation at American Heart Association. 2006

6. 6 Postprandial Hyperglycemia and Relative Risk of Death (regardless of FPG) 126 mg/dL >200 mg/dL 140-199 <140 Fasting plasma glucose 2-hour plasma glucose 2.5 2.0 1.5 1.0 0.5 0.0 Hazard ratio Adjusted for age, center, sex ; 7 year followup study DECODE Study Group. Lancet 1999;354:617–621 N=25,364

7. 7 Impact of Glycemic Variability, Glucose and A1C on Major Adverse Cardiac Events (MACE) After Acute MI Mean Amplitude Glycemic Excursion (MAGE) > 70 mg/dL was more important than A1C or glucose in predicting 1-year MACE (MI, Death, Acute heart failure) after initial AMI G Su, et al., Impact of Admission Glycemic Variability, Glucose, and Glycosylated Hemoglobin on Major Adverse Cardiac Events After Acute Myocardial Infarction, Diabetes Care, January 2013 MAGE > 70 mg/dL MAGE < 70 mg/dL p=0.001 A1C > 6.5% A1C < 6.5% p=0.091 (NS)

8. 8 Fewer Older T2D Experienced a Cardiovascular Event on Prandial Insulin Therapy vs. Basal Therapy Raz, Ceriello, et al. Post Hoc Subgroup Analysis of the HEART2D Trial Demonstrates Lower Cardiovascular Risk in Older Patients Targeting Postprandial Versus Fasting/Premeal Glycemia. Diabetes Care (34), Jul 2011 Prandial Basal Log-rank P = 0.029 Primary CV Outcomes CV death Non-fatal stroke Non-fatal MI Coronary revascularization Hospitalized acute coronary syndromes

9. 9 Increased PPG (Lower 1,5-AG) Correlates with Increased Carotid Artery Stiffness in Non-Diabetics Intima-media thickness (IMT) p=NS Pulsatility Index (PI) *p<0.05 Watanabe, et al. BMC Cardiovascular Disorders, Relationship between postprandial glucose level and carotid artery stiffness in patients without diabetes or cardiovascular disease, Feb 2013, 13:11 1,5-AG 12.71 + 3.54 A1C 5.66 + 0.32 1,5-AG 23.16 + 3.82 A1C 5.57 + 0.28 1,5-AG 12.71 + 3.54 A1C 5.66 + 0.32 1,5-AG 23.16 + 3.82 A1C 5.57 + 0.28

10. 10 33 Year Survival Depends on Baseline Glucose Tolerance Status using 2 Hour 50 g OGTT Age-adjusted survival over 33 years of follow up was dose- dependent from as low as 83 mg/dL 2 hours post glucose load Normoglycemia <96 mg/dL N=16,826 Years at Risk Survival IGT >96-199 mg/dL N=987 T2DM >200 mg/dL N=56 Brunner, et al. Relation Between Blood Glucose and Coronary Mortality Over 33 Years in the Whitehall Study. Diabetes Care 29:26–31, 2006

11. 11 For more information For a listing of postprandial hyperglycemia outcome studies, please visit www.glycomark.com/postprandialhyperglycemiawww.glycomark.com/postprandialhyperglycemia For a listing of studies about the 1,5-anhydroglucitol biomarker for postprandial hyperglycemia, please visit www.glycomark.com/product/studies www.glycomark.com/product/studies For a 3-minute overview about the 1,5-anhydroglucitol biomarker, please visit www.glycomark.com/moviewww.glycomark.com/movie