3 The Glycemic Triad HbA1c FPG PPG Long term average glucose level Basal glucose levelPeak Glucose Level
4 Duration of daily metabolic conditions BreakfastLunchDinner0:00 am4:00 amPostprandialPostabsorptiveFastingMonnier L. Eur J Clin Invest 2000;30(Suppl. 2):3–11
5 As Patients Get Closer to A1C Goal, the Need to Successfully Manage PPG Significantly Increases Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasnma glucose increments to the overall diurnal hyper glycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Diabetes Care. 2003;26:
6 Moving from A1C 8.0% to 7.0% Difficult and Important!! 20-25% of Patients Have A1Cs between 8.0% and 7.0%Moving from A1C 8.0% to 7.0% - Reduces Serious ComplicationsUKPDS Study ResultsReduced microvascular complications (kidney, eye, etc.) by 17-33%Reduced risk of heart attack by 16%Reduced diabetes-related deaths by 21%Challenge: More difficult to make improvements as A1C gets closer to 7.0%
7 Reducing A1C Levels: Reduces Incidence of Complications DCCT9 7.2%63%54%60%41%Kumamoto9 7%69%70%Improved-HbA1cRetinopathyNephropathyNeuropathyCardiovascular diseaseUKPDS8 7%17-21%24-33%-16%*NCSDCCT Research Group. N Engl J Med. 1993;329:Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:UKPDS 33: Lancet 1998; 352,Slide modified from J. Buse
8 Coronary Artery Disease and Postprandial Hyperglycemia Mellen PB et al. Arterioscler Thromb Vasc Biol. 2006;26:
9 SummaryPostprandial glycemia plays a clinically important role in the complications of diabetesPostprandial glycemia is a major contributor to overall glycemic control ESPECIALLY in moderately-well to well controlled patients
10 A1C values can be “misleading” Nearly 40% of diabetes patients in “good control” have persistently elevated glucose levels(Bonora et al. Diabetologia 2006)These patients are at high risk of developing of developing serious complications!!!!
11 So How Can We Assess Post-Prandial Glucose Control Clinically ?? Frequent fingersticksHbA1CFructosamineContinuous Glucose Monitoring SystemsSensor-Augmented Insulin Pumps
12 A New Approach to Monitoring Postprandial Hyperglycemia 1,5-Anhydroglucitol (1,5-AG)GlycoMark
16 Relationship of Blood Glucose and 1,5-AG As postprandial glucose rises in blood over the renal threshold of mg/dL glucosuria occurs.Excessive glucose in urine competitively inhibits the reabsorption of 1, 5–AG into the bloodstream at the proximal renal tubules.GLUCOSE>180 mg/dLAs glucose blood levels increase, 1,5–AG blood levels decrease.1,5–AG blood levels less than 10 µg/ml are abnormal.GLYCOMARK
17 Glycemic control markers 1,5AGFructosamine10897564312HbA1CBloodglucoseWeeks before measurement
18 GlycoMark Monitors Postprandial Hyperglycemia Dungan, K., Buse, J. et al. Diabetes Care (June 2006)Patients were sorted by glycemic excursions as measured by CGMS (AUC-180) and subdivided into two populations – bottom 50th percentile (17 patients) and top 50th percentile (17 patients).Authors’ Conclusions1,5-AG (GlycoMark) assay reflects glycemic excursions, often in the postprandial state, more robustly than other established glycemic assays.1,5-AG was reflective of varying postmeal glucose levels, despite similarities in A1Cs.In clinical practice, A1C and 1,5-AG may be used sequentially, first employing the A1C assay to identify patients who are moderately controlled and then using the 1,5-AG assay to determine the extent of postprandial glycemic excursions.18
19 GlycoMark Reveals Elevated PPG Levels in Patients with “Good” A1Cs 52 year old female with type 1 DMA1C 7.43%1,5-AG 12.4mcg/dLPPG max 195 mg/dL49 year old male with type 2 DMA1C 7.27%1,5-AG 4.5mcg/dLPPG max 235 mg/dL
20 Relationship of 1,5-Anhydroglucitol (1,5-AG) to Baseline Characteristics in Insulin-naïve Type 2 Diabetes (T2DM) Patients in the DURABLE TrialBaseline CharacteristicHbA1c ≤ 8.0%HbA1c ,5-AGHbA1c >8.0%Mean Premeal Glucosen = 5030.113*n = 527-0.179**n = 14390.403**n = 1422-0.295**Mean Postprandial Glucosen = 5020.098*n= 526n = 14370.364**n = 1421-0.270**Mean Glucosen=5030.101*n=527-0.186**n = 14410.394**n = 1424-0.293**All values are r correlations * p <0.05; ** p <0.001Authors’ Conclusions:1,5_AG had stronger correlation than HbA1c with all self-monitored plasma glucose (SMPG) parameters, particularly PPG.Additionally, at HbA1c ≤ 8.0%, 1,5-AG has a stronger correlation with blood glucose values compared with HbA1c. As such, these data support the use of 1,5-AG in conjunction with HbA1c in moderately controlled patients with T2DM.
21 GlycoMark Values vs. PPG Levels 1,5-AG (ug/ml)Approximate Mean PostmealMaximum Blood Glucose (mg/dl)> 12< 18010185819062004225< 2> 290
23 Target Glycemic GoalsGlycoMark > 10 ug/mlA1C <7.0% (6.5% AACE Goal)GlycoMark may be tested monthly
24 Clinical Study Revealing Underlying Treatment Effects Exenatide
25 Revealing Underlying Treatment Effects Exenatide Objective: To assess 1,5-AG as a marker of PPG control in Exenatide-treated patients with type 2 diabetes (T2DM)144 PatientsInitial A1C levels: 8.2 +/-1%Randomized to Exenatide (5 or 10 ug) or placeboThirty week studyPresented at ADA 2007 Annual Meeting
26 Revealing Underlying Treatment Effects Exenatide Comparison of Changes in Values from Baseline to Study EndExenatide (5 ug)Exenatide (10 ug)1,5-AG+2.7 +/- 0.6 ug/ml*45.3 +/-11.9 %+2.9 +/-0.6 ug/ml**69.4 +/-14.6 %A1C-0.5 +/-0.1 %-0.9 +/-0.1 %*** P < 0.05; ** P < 0.01Correlations: Changes from baseline1,5-AG vs. HbA1C: r = ; P <0.00011,5-AG vs. fasting plasma glucose (FPG): r = -0.54; P <0.0001
27 The Use of 1,5 – anhydroglucitol (GlycoMark) to monitor new classes of therapies for managing postmeal glucose in patients with diabetesComparison of % Changes in Values from Baseline to Study End – Treated Populations1,5-AG(Absolute % Change)A1CExenatide 5 ug(30 weeks)+ 45.3%-6.1%Pramlintide(29 weeks)+30.0%-2.4%Sitagliptin(12 weeks)+83.1%-8.6%BIAsp 70/30(28 weeks)+273.5%-29.9%
28 Patient Cases Patient HbA1c (%) GlycoMark (µg/ml) Intrepretation Male – age 1513.80.7Tests Consistent – Poor ControlFemale – age 115.622.7Tests Consistent – Good ControlFemale – age 197.42.7Tests Inconsistent – Poor PPG control indicated by GlycoMarkMale – age 145.553.3Female – age 136.24.0Female – age 155.722.214.171.124GlycoMark values <10 µg/ml are abnormal
30 “A1C is currently the gold standard measure of the quality of glycemic control.” “Alchemy is a complex subject with many different facets – literature, chemistry, fraud; searching for a gold standard in diabetes care from among the currently available tools is perhaps as futile as the quest for the Philosophers' Stone to change base metals into gold. Each tool has its limitations and the most complete picture emerges from careful application of at least two.” John Buse
31 The Glycemic Triad HbA1c FPG PPG Long term average glucose level Basal glucose levelGLYCOMARK
32 CME CREDITS FOR 1,5-ANHYDRO-D-GLUCITOL ARE NOW AVAILABLE FROM DiabetesWRAP Focus on 1,5-anhydroglucitol for Monitoring and Clinical Management of Patients with Diabetes: Implications and Relationship to Other Critical Biomarkers of Diabetes ControlPresented by Steven D. Wittlin, M.D. , Associate Professor of Medicine, Clinical Director of the Endocrine-Metabolism Division, University of Rochester School of Medicine and Dentistry, Strong Memorial Medical Center, Rochester, NY.Enrollment for this HealthWRAP is complimentary. The University of Massachusetts Medical School designates this activity for a maximum of 2 AMA PRA Category 1 Credit(s).Access atThis activity is supported by an Independent Educational Grant from Quest Diagnostics.
33 GLYCOMARKThank you for your interest in GlycoMark
Your consent to our cookies if you continue to use this website.