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Effects of sickle cell trait and hemoglobin C trait on determinations of HbA1c by an immunoassay method
W L Roberts1, M McCraw, C B Cook
1Department of Pathology, University of Mississippi Medical Center, Jackson 39216, USA. wroberts@pathology.umsmed.edu
Insights
The Bayer DCA 2000 immunoassay overestimates HbA1c in patients with HbC trait, potentially leading to overly strict diabetes management and increased hypoglycemia risk, especially in African-Americans.
Area of Science:
- Clinical Chemistry
- Diabetes Mellitus Management
- Biomarker Standardization
Background:
- Good glycemic control, measured by GHb, reduces diabetes complications.
- The National Glycohemoglobin Standardization Program (NGSP) ensures comparability of GHb measurements.
- Measurement of HbA1c in patients with hemoglobin variants is not fully addressed by NGSP.
Purpose of the Study:
- To assess the comparability of two DCCT-traceable methods for HbA1c measurement in samples with hemoglobin variants.
- To evaluate potential biases in HbA1c measurement due to hemoglobin variants.
Main Methods:
- Collected samples from diabetic and nondiabetic patients with HbAA, HbAC, and HbAS.
- Measured HbA1c using high-performance liquid chromatography (Bio-Rad Diamat) and an immunoassay (Bayer DCA 2000).
Main Results:
- Both methods showed good comparison for HbAA and HbAS samples.
- The DCA 2000 immunoassay exhibited significant positive bias (8.4-10.4%) for HbAC samples at clinically relevant HbA1c levels.
- The two methods were not comparable for HbAC samples per NGSP guidelines.
Conclusions:
- The DCA 2000 immunoassay overestimates HbA1c in individuals with HbC trait.
- This overestimation may lead to overly aggressive glycemic control and increased hypoglycemia risk.
- Clinical implications are significant for populations with high HbC trait prevalence, like African-Americans.
Objective:
A number of studies, including the Diabetes Control and Complications Trial (DCCT), have shown that good glycemic control, as assessed by GHb measurements, can reduce the chronic complications of diabetes. The National Glycohemoglobin Standardization Program (NGSP) was established to insure that GHb measurements by different methods were comparable and could be related to the candidate reference method used in the DCCT. The measurement of HbA1c in patients with Hb variants is one area not directly addressed by the NGSP. Therefore, we assessed the comparability of two DCCT-traceable methods in samples with Hb variants.
Research Design And Methods:
Samples containing HbAA, HbAC, and HbAS were collected from diabetic and nondiabetic patients. HbA1c concentrations were measured by a high-performance liquid chromatography method (Bio-Rad Diamat) and an immunoassay that is suitable for use in a physician's office (Bayer DCA 2000).
Results:
The two methods compared well for samples with HbAA and HbAS. However, for samples containing HbAC the immunoassay method showed relative positive biases of 8.4 and 10.4% at HbA1c levels of 7 and 9%, respectively, such that the two methods would not be judged comparable according to NGSP guidelines.
Conclusions:
The DCA 2000 HbA1c immunoassay method showed significant positive bias in patients with HbC trait. One possible clinical implication of this overestimation is overly rigorous glycemic control with a concomitant increase in hypoglycemia. This may be especially important in certain ethnic populations, such as African-Americans, who have a relatively high prevalence of HbC trait.
