Performance of the DCA 2000®+ Analyzer

for Measurement of Hemoglobin A1c Levels

in Children with T1DM in a DirecNet

Outpatient Clinical Trial.

Performance of the DCA2000 for Measurement of Hemoglobin A1c Levels in Children with T1DM in a DirecNet

Outpatient Clinical Trial.William Tamborlane1, Dongyuan Xing2, Michael Steffes3, Craig Kollman2, Katrina Ruedy2, Roy Beck2, Rosanna Fiallo-Scharer4, Larry Fox5, Darrell Wilson6, Eva Tsalikian7, and the Diabetes Research In Children Network (DirecNet) Study Group. 1Yale University, New Haven, CT; 2Jaeb Center for Health Research, Tampa, FL; 3University of Minnesota Central Laboratory, Minneapolis, MN; 4Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO; 5Nemours Children’s Clinic, Jacksonville, FL; 6Stanford University, Stanford, CA; 7University of Iowa, Iowa City, IA Iowa City, IA.  Background: The Bayer DCA2000 is a very popular device for measuring A1c levels that uses an immunoassay method. It requires only a small blood sample and results are available within six minutes. Objective: How DCA values compare with “gold standard” A1c values measured by ion-exchange high performance liquid chromatography in the DCCT/EDIC Central Laboratory has not been determined.Design/Methods: To examine this question, the Diabetes Research in Children Network (DirecNet) measured baseline A1c levels with the DCA2000 in 126 youth with T1DM (aged 12.2±2.7 yr.) who were participating in an outpatient clinical trial. At the same visit, a fingerstick blood sample was obtained, refrigerated, and within 7 days shipped to the DCCT/EDIC Central Laboratory. Results: The central laboratory A1c value averaged 7.9% ± 0.9% (mean ± SD), with a median (25th, 75th quartiles) of 7.7% (7.3%,

8.4%). The DCA2000 A1c values were strongly correlated (r= 0.93) but significantly higher than Central Laboratory values with a

mean difference of +0.2% (95% confidence interval +0.15 to 0.26%, p < 0.001). The absolute difference was within 0.3% for 65% of patients and within 0.5% for 86% of patients. There was some variation by clinical center (p < 0.001) with mean differences ranging between –0.1 to 0.3% at the 5 centers, but the absolute difference did not vary significantly by center (p=0.19). The mean difference also varied slightly by A1c level (slope=0.08% decrease in mean difference per 1% increase in A1c; p=0.01) but the absolute difference did not vary significantly by A1c (p=0.33). Mean and absolute differences did not vary significantly by age or gender.Conclusion: The accuracy of the DCA2000 compares very favorably with HPLC measurements of A1c performed in the

DCCT/EDIC Central Laboratory, albeit with slightly higher values.  

This research has been supported by the following NIH/NICHD Grants: HD041919-0; HD041915; HD041890; HD041918-01; HD041908-01; HD041906-01; and by Nemours Research Programs.

AbstractAbstract

BackgroundBackground

Hemoglobin A1c (A1c) was established by the Diabetes Control and Complications Trial (DCCT) as a surrogate marker for the risk of microvascular complications of Type 1 diabetes (T1DM).

DCCT and its follow-up study (EDIC) used high performance liquid chromatography (HPLC) to measure A1c in a central laboratory at the University of Minnesota.

The DCA 2000®+ Analyzer (Bayer, Inc.), which uses a cartridge method to measure A1c by immunoassay, is a popular method for measuring A1c in children with diabetes as it can be done using capillary blood and it provides results rapidly at the point of care.

ObjectivesObjectives

To examine how A1c levels measured by the DCA 2000 compare with DCCT/EDIC Central Laboratory values that have been generally considered to be the “gold standard”

To assess accuracy of DCCT/EDIC Central Laboratory results from duplicate, masked quality control samples.

MethodsMethods As part of a randomized clinical trial to assess the merits of the

GlucoWatch G2® Biographer in youth with T1DM, A1c levels were measured at baseline for 200 subjects ranging in age from 7 to 17 years (mean 12.4±2.8).

A1c was measured from a fingerstick blood sample with the DCA 2000.

A second fingerstick blood sample was obtained, refrigerated, and shipped as lysed whole blood to the Central Laboratory for measurement.

For 19 of the samples, a split-sample was collected for quality control and sent to the central laboratory as a masked sample.

Distribution of DCA 2000 and Central Laboratory A1c Values

Box plots denote minimum, 25th percentile, median, 75th percentile and maximum values. The dots in boxes denote mean values.

P-Value from paired t-test indicates mean DCA 2000 value is significantly higher than mean central laboratory value.

A1C

Val

ue

(%)

6

7

8

9

10

11

12

DCA 2000 Central Lab

. .

P-Value < 0.001

Mean=8.0% Mean=8.2%

DCA 2000 versus Central Laboratory A1c Values

6

7

8

9

10

11

12

6 7 8 9 10 11 12

Central Lab A1c Value (%)

DC

A20

00 V

alue

(%

)

Identity Line

Regression Line

DCA 2000 values correlated well with central laboratory values (Spearman correlation coefficient =0.92, p<0.001).

00.10.20.30.40.50.60.70.80.9

1

6 7 8 9 10

Central Lab A1c Value (%)

Disc

repa

ncy

(%)

Mean Discrepancy Values by A1c

Absolute Difference (p=0.50)

Difference (p<0.001)

Subjects were divided into 5 groups according to central laboratory A1c values, from low to high. Each group contains 40 subjects.

P-values are from least squares regressions. The mean difference varies significantly by A1c level.

Difference (DCA 2000 – Central Lab Value) by Clinical Sites

Dif

fere

nce

(%

) A

bso

lute

Dif

fere

nce

(%

)

Overall(N=200)

Site #1(N=40)

Site #2(N=40)

Site #3(N=40)

Site #4(N=40)

Site #5(N=40)

0.0

0.5

1.0

1.5Absolute Difference by Clinical Sites

P-Value = 0.12

P-Value < 0.001

Overall(N=200)

Site #1(N=40)

Site #2(N=40)

Site #3(N=40)

Site #4(N=40)

Site #5(N=40)

-1.0

-0.5

0.0

0.5

1.0

1.5

P-values from ANOVA indicate significant variation in mean difference but not absolute difference across clinical sites.

00.10.20.30.40.50.60.70.80.9

1

7 8 9 10 11 12 13 14 15 16 17Age (Years)

Dis

crep

ancy

(%

)Mean Discrepancy Values by Age

Difference (p=0.78)

Absolute Difference (p=0.08)

Subjects were divided into 5 groups according to age, from low to high. Each group contains 40 subjects.

P-values are from least squares regressions.

Difference (DCA 2000 – Central Lab Value) by Gender

Dif

fere

nce

(%

)

-1.0

-0.5

0.0

0.5

1.0

1.5

Female Male

P-Value = 0.90

Ab

solu

te D

iff e

ren

ce (

%)

Absolute Difference by Gender

0.0

0.5

1.0

1.5

Female Male

P-Value = 0.25

P-Values are from ANOVA.

6

7

8

9

10

6 7 8 9 10

Original Sample Value ( % )

QC

Val

ue (

% )

Duplicate Quality Control A1c Samples Measured at Central Laboratory (N=19)

Identical for 10 of 19 (53%)

Within 0.1% for 9 of 19 (47%)

ConclusionsConclusions DCA 2000 values are highly correlated with DCCT/EDIC Central

Laboratory values.

The results of this study found a small, but statistically significant tendency for the DCA 2000 to read slightly higher than the HPLC method used by the DCCT/EDIC Central Laboratory (mean difference was +0.2%).

Significant differences by clinical site in this study may suggest some variation between devices or possibly differences in technique.

Results of the split, quality control samples that were measured in this study provide further evidence of the accuracy of the Central Laboratory A1c measurements.

Barbara Davis Center

– H. Peter Chase– Rosanna Fiallo-Scharer– Jennifer Fisher– Barb Tallant

University of Iowa– Eva Tsalikian– Michael Tansey– Linda Larson– Julie Coffey– Amy Sheehan

Nemours Children’s Clinic– Tim Wysocki– Nelly Mauras– Larry Fox– Keisha Bird– Kelly Lofton

Stanford University– Bruce Buckingham– Darrell Wilson– Jennifer Block– Paula Clinton

Yale University– William Tamborlane– Stuart Weinzimer– Elizabeth Doyle– Kristin Sikes– Amy Steffen

Jaeb Center for Health Research– Roy Beck– Katrina Ruedy– Craig Kollman– Dongyuan Xing– Cynthia Silvester