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GLYCOMARK A NEW BLOOD TEST FOR PPG. Importance of Postprandial Glucose Control. The Glycemic Triad. HbA1c. Long term average glucose level. FPG. PPG. Basal glucose level. Peak Glucose Level. Breakfast. Dinner. 0:00 am. 4:00 am. Breakfast. Lunch. Postprandial.
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GLYCOMARK A NEW BLOOD TEST FOR PPG
The Glycemic Triad HbA1c Long term average glucose level FPG PPG Basal glucose level Peak Glucose Level
Breakfast Dinner 0:00 am 4:00 am Breakfast Lunch Postprandial Duration of daily metabolic conditions Postabsorptive Fasting Monnier L. Eur J Clin Invest 2000;30(Suppl. 2):3–11
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;26:881-885.
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 Complications UKPDS Study Results • Reduced 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%
Reducing A1C Levels: Reduces Incidence of Complications DCCT 9 7.2% 63% 54% 60% 41% Kumamoto 9 7% 69% 70% Improved - HbA1c Retinopathy Nephropathy Neuropathy Cardiovascular disease UKPDS 8 7% 17-21% 24-33% - 16% *NCS DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117. UKPDS 33: Lancet 1998; 352, 837-853. Slide modified from J. Buse
Coronary Artery Disease and Postprandial Hyperglycemia Mellen PB et al. Arterioscler Thromb Vasc Biol. 2006;26:189-193.
Summary • Postprandial glycemia plays a clinically important role in the complications of diabetes • Postprandial glycemia is a major contributor to overall glycemic control ESPECIALLY in moderately-well to well controlled patients
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!!!!
So How Can We Assess Post-Prandial Glucose Control Clinically ?? • Frequent fingersticks • HbA1C • Fructosamine • Continuous Glucose Monitoring Systems • Sensor-Augmented Insulin Pumps
A New Approach to Monitoring Postprandial Hyperglycemia 1,5-Anhydroglucitol (1,5-AG) GlycoMark
HO HO O O OH OH OH HO HO OH OH The structure of 1,5-anhydroglucitol (1,5AG) D-glucose 1,5-anhydro-D-glucitol (1-deoxyglucose)
Physiology of 1,5-AG Oral Supply 1,5AG (5-10mg/day) Normoglycemia Oral Supply 1,5AG (5-10mg/day) Hyperglycemia Tissues Internal Organs (500- 1000 mg) Tissues Internal Organs (500- 1000 mg) Blood Stream (1,5-AG Level Lower) Blood stream Glucose Blocks Reabsorption Kidney Kidney Urinary excretion (5-10mg/day) Urinary excretion (INCREASED)
Relationship of Blood Glucose and 1,5-AG • As postprandial glucose rises in blood over the renal threshold of 180 mg/dLglucosuria occurs. • Excessive glucose in urine competitively inhibits the reabsorption of 1, 5–AG into the bloodstream at the proximal renal tubules. GLUCOSE >180 mg/dL • As glucose blood levels increase, 1,5–AG blood levels decrease. • 1,5–AG blood levels less than 10 µg/ml are abnormal. GLYCOMARK
Blood glucose 1,5AG Fructosamine HbA1C 1 10 9 8 7 6 5 4 3 2 0 Weeks beforemeasurement Glycemic control markers
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’ Conclusions • 1,5-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
GlycoMark Reveals Elevated PPG Levels in Patients with “Good” A1Cs 52 year old female with type 1 DM A1C 7.43% 1,5-AG 12.4mcg/dL PPG max 195 mg/dL 49 year old male with type 2 DM A1C 7.27% 1,5-AG 4.5mcg/dL PPG max 235 mg/dL
Relationship of 1,5-Anhydroglucitol (1,5-AG) to Baseline Characteristics in Insulin-naïve Type 2 Diabetes (T2DM) Patients in the DURABLE Trial All values are r correlations * p <0.05; ** p <0.001 • Authors’ 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.
Target Glycemic Goals • GlycoMark > 10 ug/ml • A1C <7.0% (6.5% AACE Goal) • GlycoMark may be tested monthly
Clinical StudyRevealing Underlying Treatment EffectsExenatide
Revealing Underlying Treatment EffectsExenatide • Objective: To assess 1,5-AG as a marker of PPG control in Exenatide-treated patients with type 2 diabetes (T2DM) • 144 Patients • Initial A1C levels: 8.2 +/-1% • Randomized to Exenatide (5 or 10 ug) or placebo • Thirty week study Presented at ADA 2007 Annual Meeting
Revealing Underlying Treatment EffectsExenatide Comparison of Changes in Values from Baseline to Study End * P < 0.05; ** P < 0.01 Correlations: Changes from baseline 1,5-AG vs. HbA1C: r = - 0.74; P <0.0001 1,5-AG vs. fasting plasma glucose (FPG): r = -0.54; P <0.0001
The Use of 1,5 – anhydroglucitol (GlycoMark) to monitor new classes of therapies for managing postmeal glucose in patients with diabetes Comparison of % Changes in Values from Baseline to Study End – Treated Populations
Patient Cases GlycoMark values <10 µg/ml are abnormal
Moderately Controlled Patients (A1C <8.5%) GlycoMark (>10 mg/ml) Normal PPG GlycoMark (<10 mg/ml) Elevated PPG Target After-Meal Glucose Exenatide Sitagliptin Prandial Insulin Maintain Fasting Therapy Target Fasting Glucose Metformin Sulfonylurea Basal Insulin Utilizing GlycoMark to Reach Glycemic Goals
“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
The Glycemic Triad HbA1c Long term average glucose level FPG PPG Basal glucose level GLYCOMARK
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 Control Presented 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 at http://www.clinicalwebcasts.com/cvr_051.htm. This activity is supported by an Independent Educational Grant from Quest Diagnostics.
GLYCOMARK Thank you for your interest in GlycoMark