Comparison of Percent Total GHb With Percent HbA1c in People With and Without Known Diabetes
Abstract
OBJECTIVE: To directly compare results obtained using an ion-exchange high-performance liquid chromatography (HPLC) HbA1c method used in the Diabetes Control and Complications Trial with two different affinity chromatography methods in which ”total GHb” is determined. RESEARCH DESIGN AND METHODS: Blood was obtained from a large number of people with and without known diabetes. The specimens were divided and assayed for HbA1c and for total GHb. Total GHb was determined using a semi-automated gravity-elution boronate affinity chromatography method and an automated boronate affinity HPLC method. The results obtained with the two methods were also compared. RESULTS: In subjects without known diabetes, the mean percentage HbA1c and the range of values were similar to the total GHb values in the same subjects when assayed using the semi-automated affinity gravity-elution method (mean 5.2 ± 0.4 and 5.1 ± 0.4% [SD], respectively). With the affinity HPLC method, results were 5.3 ± 0.4%. The similarity in results was surprising. However, analysis of the data suggests that a large proportion of the material in the HbA1c fraction measured using this ion-exchange HPLC method is not GHb, as pointed out by others. Although the results were similar in people without known diabetes, in the people with diabetes, the incremental increase was ∼25% greater for the total GHb when compared with the increase in HbA1c. When corrected for the non-GHb being measured by the HbA1c method, it can be calculated that ∼40% more GHb is measured using affinity chromatography over the entire range of GHb values. CONCLUSIONS: The similarity in the mean and range of percent HbA1c and in percent total GHb using these different methods can be attributed to two factors: 1) the HbA1c ion-exchange method measures only ∼ 50–60% of the total GHb present, and 2) ∼ 40–50% of the material being measured in the HbA1c fraction is not GHb, i.e., offsetting factors fortuitously resulted in values similar to the more specific affinity methods. The greater incremental increase in percent total GHb compared with percent HbA1c in people with diabetes can be attributed to the greater amount of GHb being measured with the affinity methods.
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Boronate affinity chromatography is generally robust and less affected by hemoglobin variants, but its broader detection scope theoretically includes multiple glycated species beyond the IFCC-defined β-N-terminal glycation.
“Although this method is generally robust and less affected by hemoglobin variants, its broader detection scope theoretically includes multiple glycated species beyond the IFCC-defined β-N-terminal glycation (38,39).”
From Comparison of point‑of‑care HbA1c devices with laboratory HPLC methods: A systematic review and meta‑analysis (2026) · cites this paper as [39]
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“N‑terminal glycation (38,39).”
- Authors
- Nuttall, F. Q.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Nuttall, Frank Q
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1998-09-01
- Volume
- 21
- Issue
- 9
- Pages
- 1475-1480
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2074014290
- Cited by
- 63
- References
- 0
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- HbA1c, affinity chromatography, boronate affinity chromatography, ion-exchange HPLC, method comparison, diabetes mellitus, glycated hemoglobin measurement
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Chromatography, Affinity, Chromatography, High Pressure Liquid, Diabetes Mellitus, Female, Glycated Hemoglobin, Hemoglobins, Humans, Male, Middle Aged
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