Applying Recent A1C Recommendations in Clinical Practice

Donna M. Lisi, PharmD, BCPS, BCPP, BCGP


US Pharmacist. 2018;43(10):15-23. 

In This Article

Abstract and Introduction


Since 2010, A1C, the glycosylated form of hemoglobin, has been recognized by diabetes mellitus (DM) clinical guidelines as a diagnostic tool. Three of the latest clinical guidelines on DM address diagnosis and management. One of the guidelines, the American College of Physicians' guidance statement, has generated controversy because it has recommended higher target glycemic goals than the other recommendations. Limitations have been identified surrounding the use of A1C as a diagnostic aid in certain patient populations. Patient-specific and assay-specific interferences that exist can potentially result in inaccuracies in A1C readings.


A1C results from the nonenzymatic glycation of the amino (N)-terminal valine residue of hemoglobin A. This process is dependent on ambient glucose concentrations and occurs throughout the 120-day lifespan of the red blood cell (RBC). Therefore, A1C is used to measure glycemic control over the previous 3 months.[1–3] A1C represents a weighted average, with approximately 50% of the value due to the mean blood glucose (BG) concentrations in the 30 days prior to sampling; BG concentrations from the previous 90 to 120 days make up about 10% of the final total A1C value.[2]

A1C testing gained acceptance as a diagnostic tool for diabetes mellitus (DM) in 2009, when it was formally endorsed by an International Expert Committee that was examining its role.[4] It was later incorporated into American Diabetes Association (ADA) guidelines and was subsequently adopted by the World Health Organization.[5,6]

This shift in policy happened following the publication of the results of the Diabetes Control and Complications Trial (DCCT) and The United Kingdom Prospective Diabetes Study (UKPDS), which found that reductions in A1C resulted in decreased risk of microvascular complications in type 1 DM (T1DM) and type 2 DM (T2DM) patients, respectively.[7,8] In the 1990s, the National Glycohemoglobin Standardization Program (NGSP) was developed to formalize A1C testing. The NGSP's goal is to standardize A1C results to those of the DCCT trial, a process termed traceability.[9] The International Federation of Clinical Chemistry (IFCC) Working Group on Hemoglobin A1C Standardization has developed reference methods to assure the traceability and standardization of values assigned to A1C test calibrators and/or control materials against those used in DCCT.[10] The IFCC has also called for the reporting of A1C values as mmoL/moL rather than as a percentage, which is the reporting method used by the NGSP network and the United States. The following formula has been developed for converting between the NGSP and IFCC values:[10] NGSP = [0.09148*IFCC] + 2.152.

The ADAG (A1C-Derived Average Glucose) study found a strong correlation between the A1C and estimated average glucose concentrations.[11,12] A change (either positive or negative) in A1C percentage of 0.5% is considered clinically significant.[13] See Table 1.[14]

Three clinical guidelines published in 2018 that have addressed the utilization of A1C in the diagnosis and management of DM include the ADA Standards of Medical Care in Diabetes 2018, the Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) on the Comprehensive T2DM Management Algorithm—2018 Executive Summary, and the guidance statement update from the American College of Physicians (ACP) on A1C targets for glycemic control with pharmacologic therapy for nonpregnant adults with T2DM.[15–17] This article will review these recommendations, as well as limitations and interferences with A1C testing.