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Part 2 Routinely Identifying Postprandial Hyperglycemia - Challenges & Tools

An Educational Service from GLYCOMARK

GLYCOMARK 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

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Looking Beyond a “Good” A1C of 7%

70

180200

300

400

50

mg/dL

Breakfast Lunch Dinner Bedtime

185

154

123

Range ofEstimatedAverageGlucose

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%

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Postprandial Hyperglycemia Assessment ToolsTool Description Drawbacks

HbA1C Mean of last 60-90 days

• Can mask extremes; cannot change quickly• Interferences (hemoglobinopathies)• Individual variability in glycosylation rates

Fructosamine Mean 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; GLYCOMARK)

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

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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

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1,5-Anhydroglucitol (1,5-AG)A monosaccharide similar to glucose

O

OH

OH

HO

HO OH

O

OH

OH

HO

HO

1,5-anhydroglucitol1,5-anhydro-D-glucitol

1-deoxyglucoseD-glucose

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1,5-Anhydroglucitol Found in Most Foods

Highest content - soybeans, grains, rice, pasta, beef, pork, tea

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Physiology of 1,5-Anhydroglucitol (1,5-AG)Why 1,5-AG decreases with hyperglycemia

1,5-AGFood 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 excretedin urine

Normoglycemia Hyperglycemia

Excess glucoseblocks 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-AGDigested

Tissue pool of 1,5-AG

Tissue pool of 1,5-AG

Kidney Kidney

LiverProduction

LiverProduction

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1,5-Anhydroglucitol – The “Good” SugarInverse relationship to glucose

Mean Max Glucose

1,5-AG

<140 mg/dL

300+ mg/dL

20+µg/ml

1 µg/ml

Extremehyperglycemic

excursionsNormoglycemia

<10µg/mLfrequent

peaks over180 mg/dL

<6µg/mL frequent

peaks over200 mg/dL

>20µg/mL Median - No

diabetes

<14µg/mL normally found in diabetes

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180230

0

50

100

150

200

250

Patient Group 1 Patient Group 2

CGM Postmeal Glucose (mg/dL)(P<0.05)

7.20 7.38

0.00

2.00

4.00

6.00

8.00

Patient Group 1 Patient Group 2

A1C (%)8.00

5.58

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

Patient Group 1 Patient Group 2

GlycoMark 1,5-AG (mg/ml)(P<0.05)

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 50th percentile (Group 1) and top 50th percentile (Group 2)

1,5-AG Correlation with CGMMean Postmeal Maximum Glucose (MPMG)

CGM MPMG (mg/dL)P < 0.05

A1C (%)P < 0.05Not statistically different

Group 1 Group 2 Group 1 Group 2 Group 1 Group 2

1,5-AG (µg/mL)

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A1C Can Mask Hyperglycemic Excursions

0

50

100

150

200

250

300

350

400

2/15 2/16 2/17 2/18 2/19 2/20 2/21 2/22

Time (days)

Glu

co

se (m

g/d

L)

0

50

100

150

200

250

300

350

400

2/8 2/9 2/10 2/11 2/12 2/13 2/14 2/15

Time (days)

Glu

co

se (

mg

/dL

)

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

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For more information

• For a listing of postprandial hyperglycemia outcome studies, please visit www.glycomark.com/postprandialhyperglycemia

• For a listing of studies about the 1,5-anhydroglucitol biomarker for postprandial hyperglycemia, please visit www.glycomark.com/product/studies

• For a 3-minute overview about the 1,5-anhydroglucitol biomarker, please visit www.glycomark.com/movie