2.2.0.0 A1C Lim­i­ta­tions

The A1C test is an in­di­rect mea­sure of av­er­age glycemia and, as such, is sub­ject to lim­i­ta­tions. As with any lab­o­ra­to­ry test, there is vari­abil­i­ty in the mea­surement of A1C. Al­though such vari­abil­i­ty is less on an in­train­di­vid­u­al basis than that of blood glu­cose mea­surements, clin­i­cians should ex­er­cise judg­ment when using A1C as the sole basis for as­sess­ing glycemic con­trol, par­tic­u­lar­ly if the re­sult is close to the thresh­old that might prompt a change in med­i­ca­tion ther­a­py. Con­di­tions that af­fect red blood cell turnover (hemolyt­ic and other ane­mias, glu­cose-‍6-‍phos­phate de­hy­dro­ge­nase deficien­cy, re­cent blood trans­fu­sion, use of drugs that stim­u­late ery­thro­poe­sis, end-‍stage kid­ney dis­ease, and preg­nan­cy) may re­sult in dis­crep­an­cies be­tween the A1C re­sult and the pa­tient’s true mean glycemia. Hemoglobin vari­ants must be con­sid­ered, par­tic­u­lar­ly when the A1C re­sult does not cor­re­late with the pa­tient’s SMBG lev­els. How­ev­er, most as­says in use in the U.S. are ac­cu­rate in in­di­vid­u­als het­erozy­gous for the most com­mon vari­ants (www.ngsp.org/‍interf.asp). Other mea­sures of av­er­age glycemia such as fruc­tosamine and 1,5-‍an­hy­droglu­ci­tol are avail­able, but their trans­la­tion into av­er­age glu­cose lev­els and their prog­nos­tic significance are not as clear as for A1C. Though some vari­abil­i­ty in the re­la­tion­ship be­tween av­er­age glu­cose lev­els and A1C ex­ists among dif­fer­ent in­di­vid­u­als, gen­er­ally the as­so­ci­a­tion be­tween mean glu­cose and A1C with­in an in­di­vid­u­al cor­re­lates over time (5).

A1C does not pro­vide a mea­sure of glycemic vari­abil­i­ty or hy­po­glycemia. For pa­tients prone to glycemic vari­abil­i­ty, es­pe­cial­ly pa­tients with type 1 di­a­betes or type 2 di­a­betes with se­vere in­sulin deficien­cy, glycemic con­trol is best eval­u­ated by the com­bi­na­tion of re­sults from SMBG or CGM and A1C. A1C may also in­form the ac­cu­ra­cy of the pa­tient’s meter (or the pa­tient’s re­port­ed SMBG re­sults) and the ad­e­qua­cy of the SMBG test­ing schedule.