The document summarizes research on using estimated average glucose (eAG) levels derived from HbA1c measurements to help patients better understand their diabetes control. A large international study found a strong correlation between HbA1c levels and average glucose levels over time across different populations with diabetes. Reporting eAG values alongside HbA1c test results can help patients and clinicians interpret HbA1c in terms of average blood sugar, improving diabetes education and management.

1. Use of the
Estimated Average
Glucose (eAG) in
Patient Care
www.diabetes.org 1-800-DIABETES

2. A Typical Patient Encounter
“So, Mrs. Smith, it looks like
you do have diabetes. Your
repeat fasting blood sugar was
178, and as you recall the first
one was 187. Over 126 is
diabetes. Also, your
hemoglobin A1c was way too
high at 8.6%. Normal is less
than 6%. We need to get it
below 7%.”
www.diabetes.org 1-800-DIABETES

3. A Typical Patient Encounter
“What’s a hemoglobin A…
whatever you said? I
remember my hemoglobin
was low when I was
pregnant. What were those
other numbers? What do
you mean, 7%...of what?”
www.diabetes.org 1-800-DIABETES

4. G G G G
G G
G
G
G
G G
G ÷ G = __%
GG
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5. Uh…
???
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6. It’s Not Just Confusing for
Newly Diagnosed Patients
• High levels of testing of HbA1c for
patients with known diabetes (> 90%).
• Of patients with test in past 6 months:
– 66% did not know result
– 25% accurately reported within 1% range
(< 7%, 7-8%, 8-9%)
– 9% inaccurately reported within 1% range
Heisler, Diabetes Care 28:816,2005
www.diabetes.org 1-800-DIABETES

7. The Clinical Dilemma
• HbA1c: useful for research, risk
prediction, target of therapy
• Well standardized
• HOWEVER, difficult to explain to patients
• Concept of % is not intuitive
• Glucose more familiar to patients from
self-monitoring or from laboratory glucose
results
www.diabetes.org 1-800-DIABETES

8. The Concept of Average Glucose
• We tell patients the HbA1c reflects their
“average glucose over 2-3 months”
• But: do we know this for sure?
www.diabetes.org 1-800-DIABETES

9. Study Year Cohort Study period Number of
(weeks) glucose tests
per patient
per 1-3 months
Svendsen 1982 15 T1DM 5 200-300
Nathan 1984 21 T1DM 8 200-300
DCCT 2002 1439 T1DM 12 7
Hempe 2002 128 T1DM 4 80
Murata 2004 182 T2DM 8 180
Nathan 2007 22 T1DM 12 24,000
3 Normals (CGMS)
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10. The A1C-Derived Average Glucose
(ADAG) Study
International study designed to:
• Carefully look at relationship between HbA1c and
average glucose
• Determine the mathematical relationship between
the two for reliable conversion
• Establish that the relationship is valid across:
- Diabetes types
- A wide range of HbA1c levels and age
- Different races/ethnicities
Nathan et al, Diabetes Care 31:1473, 2008
www.diabetes.org 1-800-DIABETES

11. ADAG Study Centers
• Cameroon • United States
• Denmark – Boston
– New York
• Italy – San Antonio
– Seattle
• The Netherlands
• India (site dropped
due to specimen
handling issues)
www.diabetes.org 1-800-DIABETES

12. Participants in ADAG
• Goal was to recruit people with
– Type 1 diabetes
– Type 2 diabetes
– No diabetes
• With a range of
– Ethnicity/race
– HbA1c levels
• Excluded those with conditions that
would interfere with
measurement/interpretation of HbA1c or
glucose
www.diabetes.org 1-800-DIABETES

13. Measures of Glycemia in ADAG Study
• CGM (calibrated by 8-point glucose profiles with
Hemocue meter) for at least 48 hours at baseline
and every month for 3 months
• 7-point glucose profiles for 3 days per week with
One Touch Ultra meter
• HbA1c at baseline and monthly X 3 months with
DCCT-aligned assay in a central laboratory
• Four measures of HbA1c to assure stable control,
but only final value used for correlation with prior
3 months’ glucose readings
www.diabetes.org 1-800-DIABETES

14. ADAG Study Flow
Total Enrolled 661
Eliminated from analysis 154 (23%)
- Dropped out or excluded 91 (14%)
during study
- Inadequate CGM 11 (2%)
- Inadequate HbA1c samples 52 (8%)
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15. Baseline Characteristics of ADAG
Participants
Type 1 Type 2 Non-DM Total
Number 268 159 80 507
Age 43 + 13 56 + 9 40 + 14 46 + 14
Gender (% F) 52% 50% 69% 54%
Race/Ethnicity
White 93% 73% 71% 83%
African/Af-Am 2% (5) 13% (21) 15% (12) 8% (38)
Hispanic 6% (15) 8% (12) 15% (12) 8% (39)
Treatment
Pump / ≥3 inject/day 47% / 53%
Diet only/ 10%
Oral agent only 52%
Insulin only 19%
Insulin & oral 19%
www.diabetes.org 1-800-DIABETES

16. ADAG Study: Distribution of Baseline
HbA1c
400
350
Number 300
44%
of
38%
250
subjects Normal
200
150 D
i
18%
a
100 b
e
50 t
i
0 c
4-6.5 6.6-8.5 >8.5
Baseline HbA1c (%)
www.diabetes.org 1-800-DIABETES

17. ADAG Study: Glucose Monitoring
• CGM – mean of ~ 2,400 measurements per
participant
• LifeScan meter ~ mean of 300 measurements per
participant
– Mean of ~ 25 measurements per week
– Goal was a minimum of 21 tests per week
• Total ~ 2,700 measurements/participant during 12
weeks
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18. ADAG Study: Analyses
• CGM results corrected upward by 5% to be
consistent with BG
• Each glucose measure weighted in proportion to
the inverse of total number of measurements on
that day (each day had equal weight)
• Arithmetic mean glucose calculated for each
participant
• Linear regression model used to estimate
relationship between average glucose and the
3-month HbA1c
www.diabetes.org 1-800-DIABETES

19. ADAG Study: Study Success
18
16
90% of
14 cohort values
Calc. AG (mmol/
12 fall in this range
10
8
6
4
L)
2
0
HbA1c (%)
90% of values fell within +/- 15%
www.diabetes.org 1-800-DIABETES

20. ADAG Study: Correlation of AG
With HbA1c
AG (mg/dl) = 28.7 x HbA1c – 46.7
R2 = 0.84
AG (mg/dl)
P < 0.0001
HbA1c (%)
www.diabetes.org 1-800-DIABETES

21. ADAG Study: Correlation of AG
with HbA1c: CGM data vs. Meter
18
CGM calc. AG = 1.649x - 2.645
16 2
R = 0.768
14
Calc. AG (mmol/L)
12
10 No difference in
8
relationship (P=0.18)
whether LifeScan or
6
CGMS data used
Lifescan calc. AG = 1.574x HbA1c- 2.547
4
R2 = 0.802
2
0
3 4 5 6 7 8 9 10 11 12 13
HbA1c (%)
www.diabetes.org 1-800-DIABETES

22. ADAG Study: Other Factors Examined
• Does the HbA1c-Average Glucose relationship
differ by:
- Type 1 or type 2 diabetes NO
- Diabetes or no diabetes NO
- Amount of glucose variability NO
- Gender NO
- Age NO
- Ethnicity/Race NO
(but trend toward higher HbA1c per AG in African
and African-American participants vs. whites, P=0.07)
- Smoking NO
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23. ADAG Study Excluded Known Sources
of “Inaccuracy” of HbA1c
• Hemoglobinopathy
• Anemia
• Pregnancy
• Hepatic or renal disease
• Etc.
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24. ADAG Study Conclusion:
HbA1c Correlates Highly With AG
450
400
350 AG (mg/dl) = 28.7 x HbA1c – 46.7
AG (mg/dl)
300
250
200
150
100
50
3 4 5 6 7 8 9 10 11 12 13
Measured HbA1c (%)
www.diabetes.org 1-800-DIABETES

25. Implications
• Tight correlation between HbA1c and AG
allows us to translate HbA1c into an
estimated Average Glucose (eAG)
• eAG will apply to the majority of patients
with diabetes
– Barring “traditional” conditions interfering
with the assay or the relationship between
glycemia and HbA1c
www.diabetes.org 1-800-DIABETES

26. ADAG Study: “Translation” of
HbA1c into eAG
eAG
HbA1c (%) (mg/dl) (mmol/l)_
5 97 5.4
6 126 7.0
7 154 8.6
8 183 10.2
9 212 11.8
10 240 13.4
www.diabetes.org 1-800-DIABETES

27. Note that the numbers are different
ADAG DCCT
HbA1c (%) (mg/dl)___(mg/dl)______
6 126 135
7 154 170
8 183 205
9 212 240
10 240 275
www.diabetes.org 1-800-DIABETES

28. Consensus Statement FCC, EASD, IDF, ADA
Sept 2007)
• HbA1c assay to be standardized
worldwide using the new IFCC standard
and expressed as:
– % as currently used (DCCT values)
– IFCC units in mmol HBA1c/mol HbA
– eAG in mmol/l or mg/dL (if ADAG study meets its data
acceptability goals)
• This paved the way for reporting both
HbA1c and EAG on lab reports
Diabetes Care and Diabetologia, 2007
www.diabetes.org 1-800-DIABETES

29. What Won’t Change…And What’s New
• To a clinician, there is no change in the
HbA1c assay
• To clinical chemists, there is a new IFCC
standard in the background
• We have the potential for a valuable
educational tool for patients
www.diabetes.org 1-800-DIABETES

30. A Typical Patient Encounter
“So, Mrs. Smith, it looks like you do
have diabetes. Your average blood
sugar is around 200. When people
don’t have diabetes, this number
is below 125. We need to work
with you to try to get this number,
the average glucose, down below
150 over the next few months with
some weight loss, exercise, and a
medication. Let’s talk some more
about what you can do…”
www.diabetes.org 1-800-DIABETES

31. A Typical Patient Encounter
“Wow, I’m not happy to hear
that…I know that diabetes
can do some bad things. Tell
me what I can do to get my
average glucose down.”
www.diabetes.org 1-800-DIABETES

32. What is ADA Doing to Promote
Use of eAG in Patient Care?
• Health care provider education
– ADA Scientific Sessions, June ’08
– American Association of Clinical Chemists, August ‘08
– AADE Annual Meeting, August ‘08
– eAG calculators (handheld and on professional.diabetes.org)
• Patient education
– Website
– Diabetes Forecast magazine, books
– Pamphlets and brochures
– ADA will include term “average glucose” in all consumer pieces
www.diabetes.org 1-800-DIABETES

33. What Can Clinicians and
Educators Do?
• Choose which term—A1C or Average Glucose—
to use with each patient (some may already be
used to A1C)
• In verbal communications, no need to say
“estimated”
• We want to keep the A in A,B,Cs
• Use updated table, calculator on
www.diabetes.org, or other tools to convert A1C
to average glucose
• “Lobby” your lab to report both numbers
www.diabetes.org 1-800-DIABETES

34. What Can Clinical Chemists Do?
• Even with tools, most clinicians will not take the
time to calculate conversions
• Reporting both HbA1c (DCCT-aligned) AND eAG
on lab reports will do the most to promote wide
use of the term
• Professional and patient education may drive
demand
• Conversion is a simple regression equation
www.diabetes.org 1-800-DIABETES

35. Average Glucose
Blood pressure
Cholesterol
to help make the “A” understandable!
www.diabetes.org 1-800-DIABETES