Use of the
Estimated Average
Glucose (eAG) in
Patient Care
www.diabetes.org
1-800-DIABETES
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
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
G
G
G
G
G
G
G
G
G G
G
www.diabetes.org
G

G
GG
=
__%
1-800-DIABETES
Uh…
???
www.diabetes.org
1-800-DIABETES
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
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
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
Year
Cohort
Study period
(weeks)
Number of
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
3 Normals
12
24,000
(CGMS)
Study
www.diabetes.org
1-800-DIABETES
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
ADAG Study Centers
• Cameroon
• Denmark
• Italy
• The Netherlands
• United States
–
–
–
–
Boston
New York
San Antonio
Seattle
• India (site dropped
due to specimen
handling issues)
www.diabetes.org
1-800-DIABETES
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
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
ADAG Study Flow
Total Enrolled
661
Eliminated from analysis
154 (23%)
- Dropped out or excluded
during study
91 (14%)
- Inadequate CGM
11 (2%)
- Inadequate HbA1c samples
52 (8%)
www.diabetes.org
1-800-DIABETES
Baseline Characteristics of ADAG
Participants
Type 1
Type 2
Non-DM
Total
268
159
80
507
43 + 13
56 + 9
40 + 14
46 + 14
52%
50%
69%
54%
93%
73%
71%
83%
African/Af-Am
2% (5)
13% (21)
15% (12)
8% (38)
Hispanic
6% (15)
8% (12)
15% (12)
8% (39)
Number
Age
Gender (% F)
Race/Ethnicity
White
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
ADAG Study: Distribution of Baseline
HbA1c
400
350
Number 300
of
250
subjects
200
38%
Normal
150
18%
D
i
a
b
e
t
i
c
100
50
0
44%
4-6.5
6.6-8.5
>8.5
Baseline HbA1c (%)
www.diabetes.org
1-800-DIABETES
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
www.diabetes.org
1-800-DIABETES
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
ADAG Study: Study Success
18
16
90% of
cohort values
fall in this range
14
12
10
8
6
4
2
0
HbA1c (%)
90% of values fell within +/- 15%
www.diabetes.org
1-800-DIABETES
AG (mg/dl)
ADAG Study: Correlation of AG
With HbA1c
AG (mg/dl) = 28.7 x HbA1c – 46.7
R2 = 0.84
P < 0.0001
HbA1c (%)
www.diabetes.org
1-800-DIABETES
ADAG Study: Correlation of AG
with HbA1c: CGM data vs. Meter
18
CGM calc. AG = 1.649x - 2.645
Calc. AG (mmol/L)
16
2
R = 0.768
14
12
No difference in
relationship (P=0.18)
whether LifeScan or
CGMS data used
10
8
6
4
2
0
3
4
5
6
7
8
9
10
11
12
HbA1c (%)
www.diabetes.org
1-800-DIABETES
13
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
www.diabetes.org
1-800-DIABETES
ADAG Study Excluded Known Sources
of “Inaccuracy” of HbA1c
•
•
•
•
•
Hemoglobinopathy
Anemia
Pregnancy
Hepatic or renal disease
Etc.
www.diabetes.org
1-800-DIABETES
ADAG Study Conclusion:
HbA1c Correlates Highly With AG
450
400
AG (mg/dl)
350
AG (mg/dl) = 28.7 x HbA1c – 46.7
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
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
ADAG Study: “Translation” of
HbA1c into eAG
HbA1c (%)
5
6
7
8
9
10
www.diabetes.org
eAG
(mg/dl)
(mmol/l)_
97
5.4
126
7.0
154
8.6
183
10.2
212
11.8
240
13.4
1-800-DIABETES
Note that the numbers are different
HbA1c (%)
6
7
8
9
10
www.diabetes.org
ADAG
DCCT
(mg/dl)___(mg/dl)______
126
135
154
170
183
205
212
240
240
275
1-800-DIABETES
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
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
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
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
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
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
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
Average Glucose
Blood pressure
Cholesterol
to help make the “A” understandable!
www.diabetes.org
1-800-DIABETES