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I agree completely with Jonathan Middle's comments about DCCT
"standardisation" of methods.

I understand the argument that the DCCT method must be kept as a reference
because there is so much clinical data that is based upon it.  In that
case, would it have been acceptable to use an ancient gravimetric technique
as a reference method for calcium, simply because the original reference
ranges were derived using that method, and then correct the results from
more modern techniques forever afterwards?

The problem is that the DCCT method was first published in 1985. 
Chromatography has moved on since then, and there are HPLC methods
available which can separate more minor fractions from HbA1c.  These
fractions co-elute with HbA1c in the DCCT method, so it gives higher
results than most other chromatographic methods.

The calibrators that some manufacturers provide for "DCCT correction" are
lyophilised, yet we know that many methods are affected by the sample
matrix (see WEQAS reports).

The method I use (in-house : PolyCAT weak cation exchange column) provides
virtual baseline separation of HbA1c from the fraction which elutes next,
although I know that there is an acetylated fraction which co-elutes with
HbA1c, as it does in most HPLC methods.  This method still gives results,
however, which are 1.0 to 1.5% lower than a "DCCT method".  If I add on the
percentage area of the fraction which elutes after HbA1c, the results are
much closer to "DCCT values"!!  Nevertheless, I have been forced into
deriving a "fiddle factor" so that we can report "DCCT-corrected" HbA1c
values.

I can envisage that there will still be problems even after the
introduction of a true HbA1c standard by the IFCC.  If a chromatographic
method suffers from co-elution of minor fractions with HbA1c, then
calibration of these will still be a fudge, bearing in mind that there is
inter-individual variation in these fractions.

We need better methods in addition to a true HbA1c calibrant.

Phillip Jordan
Clinical Scientist
Royal Devon and Exeter Hospital



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