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Golden S, Boulware LE, Berkenblit G, et al. Use of Glycated Hemoglobin and Microalbuminuria in the Monitoring of Diabetes Mellitus. Rockville (MD): Agency for Healthcare Research and Quality (US); 2003 Oct. (Evidence Reports/Technology Assessments, No. 84.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Use of Glycated Hemoglobin and Microalbuminuria in the Monitoring of Diabetes Mellitus.

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Appendix C. Glycohemoglobin (GHb) Testing

GHb (glycated hemoglobin, HbA1c, HbA1) describes a series of stable minor hemoglobin components formed slowly and nonenzymatically from hemoglobin and glucose. This alteration in HbA is a post-translational modification [4644].

Rahbar et al. demonstrated elevation in the minor HbA fractions in patients with diabetes using gel electrophoresis (Rahbar, et al. 1969; [92177]; Rahbar, et al. 1986 [92178]).

Historical perspective:

HbA1 can be separated into three minor components that have a more negative charge:

  1. HbA1a
  2. HbA1b
  3. HbA1c

HbA1c was the component resulting from post-translational modification of HbA by glucose at the N-terminus of the β chain. HbA1c has been correlated with:

  1. fasting plasma glucose
  2. glucose peak during glucose tolerance test
  3. area under the curve of glucose tolerance test
  4. mean glucose levels over preceding few weeks

[4644].

Glycohemoglobin nomenclature:

Terminology
HbAThe major form of hemoglobin; a native, unmodified tetramer consisting of two α- and β-chains
GHbGeneral term for glucose bound nonenzymatically to hemoglobin with a ketoamine structure
HbA1GHb species that are more negatively charged forms of HbA detected by cation-exchange chromatographic and electrophoretic methods, which include HbA1a, HbA1b, and HbA1c, “fast” hemoglobins
HbA1cSpecific GHb that is an adduct of glucose attached to the β-chain terminal valine residue
Total GHbTerm used to describe all GHb species as measured by affinity chromatographic methods

Glycated hemoglobin measurement methods available in US as of 2002

Common interferences
Glycated Hb MeasuredNGSP CertifiedHbSHbCElevated HbFHbE
Ion Exchange Chromatography
 Bio-Rad DiaStatHbA1c
 Bio-Rad VariantHbA1cYesYesNo-No
Total GHbNoNo--
 Bio-Rad Variant IIHbA1cYesNoNoNo (HbF≤24%)Yes
 Tosoh A1c 2.2 PlusHbA1cYesNoNo-Yes
 Tosoh G7 AutoHbA1cYes
 Other: MinicolumnsNo
Boronate Affinity
 Abbott IMxHbA1cNoYes--
Total GHb
 Abbott VisionTotal GHb
 Primus HPLCHbA1cYesNoNo-No
 Axis ShieldYesNoNo--
  NycoCard (Primus)
 Provalis GlycosalYes
  Bio-Rad MicroMat IINoYes--
  Cholestech
 Other: Minicolumns
Electrophoresis
 Beckman DiatracHbA1c
Immunoassay
 Bayer DCA 2000HbA1cYesNoNo-No
 Beckman SynchronHbA1cYesNoNo--
 Dade Behring DimensionHbA1cYes
 Roche Cobas IntegraHbA1cYesYesYes--
 Roche UnimateYesYesYes--
 Roche Tina-quant IIYesNoNoNo (HbF≤30%)No
 Metrika A1c NowYes

Adapted from National Glycohemoglobin Standardization Program Website(www​.ngsp.org).

College of American Pathologists (CAP) Survey Data (updated 5/02)

The American Diabetes Association (ADA) recommends that laboratories use only GHB assay methods that have been NGSP certified and report results as “%HbA1c” or “%HbA1c equivalents”. The ADA also recommends that all laboratories performing GHB testing participate in the College of American Pathologists (CAP) fresh sample proficiency testing survey (see ADA Recommendations section on this website for more details). The following methods were included in the recent 2002 CAP GH2 survey:

Methods reporting HbA1c or equivalent:

Bayer DCA 2000

Beckman Synchron Syst

Bio-Rad Diastat

Bio-Rad Variant A1c

Bio-Rad Variant II A1c

Dade Behring Dimension

Primus (affinity)

Roche Cobas Integra

Roche/Hitachi (Tina Quant II)

Tosoh A1c 2.2 Plus

Tosoh G7 Auto HPLC

Abbott IMX

Beckman Diatrac

Methods reporting total GHb:

Abbott IMX

Bio-Rad Variant

Helena Glyco-Tek

Primus

Adapted from NGSP Website (www.ngsp.org).

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