1. 1 Part 2 Routinely Identifying Postprandial Hyperglycemia - Challenges & Tools 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 Looking Beyond a “Good” A1C of 7% 70 180 200 300 400 50 mg/dL BreakfastLunchDinnerBedtime 185 154 123 Range of Estimated Average Glucose A1C may not reflect postprandial extremes due to blood glucose averaging and individual variability D Nathan et al, Translating the A1C Assay into Average Glucose Values, Diabetes Care, Vol. 31, No. 8, Aug 2008        Fingerstick tests may miss glucose peaks due to timing A1C 7% 

3. 3 Postprandial Hyperglycemia Assessment Tools ToolDescriptionDrawbacks HbA1CMean of last 60-90 days Can mask extremes; cannot change quickly Interferences (hemoglobinopathies) Individual variability in glycosylation rates FructosamineMean of last 3-4 weeks Can mask extremes Individual variability in glycosylation rates Oral Glucose Tolerance Test (75 gr load) Multiple data points on one day Good measure of postprandial glucose but time-consuming for patients and providers Only measures one day in time so could be skewed by illness or stress Continuous Glucose Monitors 24/7 continuous blood glucose measurements Excellent tool but cost and reimbursement is issue for T2D and some T1D Time-consuming training and report review Some patients will not wear sensor 24/7 Frequent Fingerstick Blood Glucoses Single data points Can miss peaks due to timing Patient adherence to frequent PPG testing Cost and insurance limits on BG strip quantity Unreadable/inaccurate glucose logbooks 1,5-Anhydroglucitol (1,5-AG; G LYCO M ARK ) 1-2 week measure of average peak blood glucose Not accurate in advanced kidney or liver disease Individual variability in renal thresholds especially during pregnancy

4. 4 1,5-Anhydroglucitol (1,5-AG) Provides an estimated average peak glucose (eAPG) over the previous 1-2 weeks Used when continuous glucose monitor or frequent postprandial fingerstick glucose tests not available Non-fasting serum or plasma test that can be used as routine marker for PPH Typically ordered when A1C is 6-8% and to monitor therapy change impact on PPH

5. 5 1,5-Anhydroglucitol (1,5-AG) A monosaccharide similar to glucose O OH HO OH O HO 1,5-anhydroglucitol 1,5-anhydro-D-glucitol 1-deoxyglucose D-glucose

6. 6 1,5-Anhydroglucitol Found in Most Foods Highest content - soybeans, grains, rice, pasta, beef, pork, tea

7. 7 Physiology of 1,5-Anhydroglucitol (1,5-AG) Why 1,5-AG decreases with hyperglycemia 1,5-AG Food intake (5-10 mg) Blood stream Urinary 1,5-AG excretion limited (5-10 mg) 1,5-AG Food intake (5-10 mg) Blood stream Large amounts of 1,5-AG excreted in urine Normoglycemia Hyperglycemia Excess glucose blocks 1,5-AG reabsorption Most 1,5-AG is reabsorbed in renal tubules Serum 1,5-AG stays HIGH Serum 1,5-AG is LOW 1,5-AG Digested 1,5-AG Digested Tissue pool of 1,5-AG Tissue pool of 1,5-AG Tissue pool of 1,5-AG Tissue pool of 1,5-AG Kidney Liver Production Liver Production

8. 8 1,5-Anhydroglucitol – The “Good” Sugar Inverse relationship to glucose Mean Max Glucose 1,5-AG <140 mg/dL 300+ mg/dL 20+µg/ml 1 µg/ml Extreme hyperglycemic excursions Normoglycemia <10µg/mL frequent peaks over 180 mg/dL <6µg/mL frequent peaks over 200 mg/dL >20µg/mL Median - No diabetes <14µg/mL normally found in diabetes

9. 9 Dungan, K., Buse, J. et al. Diabetes Care, June 2006 Authors’ Conclusions 1,5-AG reflects CGM glycemic excursions (MPMG and AUC/180) more robustly than fructosamine or A1C 1,5-AG reflected varying postmeal glucose levels, despite similar A1Cs 1,5-AG may be a useful adjunct to A1C in moderately controlled T2D where SBGM is infrequent and often only in fasting state Patients sorted by glycemic excursions as measured by CGMS (AUC-180) and subdivided into two populations – bottom 50 th percentile (Group 1) and top 50 th percentile (Group 2) 1,5-AG Correlation with CGM Mean Postmeal Maximum Glucose (MPMG) CGM MPMG (mg/dL) P < 0.05 A1C (%) P < 0.05 Not statistically different Group 1 Group 2 1,5-AG (µg/mL)

10. 10 A1C Can Mask Hyperglycemic Excursions Renal Threshold 52 year old female A1C 7.43% 7 Days of Continuous Glucose Monitoring 49 year old male A1C 7.27% Ave. CGM Max Glucose 195 mg/dL Ave. CGM Max Glucose 235 mg/dL 1,5-AG marker measures blood glucoses >180 mg/dL Dungan, K., Buse, J. et al. Diabetes Care, June 2006 6 spikes 18 spikes 1,5-AG 12.4 µg/mL 1,5-AG 4.5 µg/mL

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