Estimated Average Glucose (eAG) Underestimates Mean Blood Glucose

The A1c-derived Average Glucose study recommended reporting A1c in estimated average glucose (eAG) equivalents. Researchers at Louisiana State University Health Sciences Center, and the Research Institute for Children, Children's Hospital, both in New Orleans, LA, compared eAG with self-monitored mean blood glucose (MBG) to determine if eAG is systematically biased due to biological variation in the relationship between MBG and A1c.  

MBG and A1c were recorded from charts of 202 pediatric Type 1 diabetes patients at 1,612 clinic visits. Patients were divided into groups with low, moderate, or high A1c bias based on a hemoglobin glycation index (HGI).

MBG vs. eAG (mg/dl, mean±SD): total population, 194±34 vs. 196±36; low HGI group, 186±31 vs. 163±20; moderate HGI group, 195±28 vs. 193±19; high HGI group, 199±42 vs. 230±31.

The ADAG study concluded that A1c could be reliably translated into eAG based on the linear relationship between A1c and mean blood glucose measured by continuous glucose monitoring in a mixed population of diabetic and non-diabetic subjects. This conclusion assumes that all population variation in A1c is either random or due to variation in blood glucose concentration. However, numerous reports of biological variation in A1c (7-13) indicate that this assumption is false. The researchers had previously developed HGI to quantify biological variation in A1c due to factors other than blood glucose concentration and showed that HGI was quantitatively consistent within individuals over time, different between individuals, normally distributed and positively correlated with risk for complications. The fact that many patients have HGI values that are always positive or always negative indicates that HGI measures systematic A1c bias between individuals.

The present study demonstrates that this systematic A1c bias makes eAG a systematically biased estimate of MBG downloaded from patient glucose meters in high and low HGI patients. It is important to emphasize that the present study used routine A1c and MBG data typical of that available in most diabetes clinics. If A1c is reported as eAG, patients and clinicians will be confronted with significant discrepancies between eAG and self-monitored MBG which will confound interpretation of glycemic control. 

Furthermore, treating patients based on eAG alone could result in inappropriate medical decisions. Based on the results, if low HGI patients are intensively managed to a low eAG target their MBG would presumably remain above the target, inadvertently leaving these patients at unnecessary risk for chronic complications. Conversely, intensive management could drive MBG in high HGI patients below the eAG target which presumably would increase their risk for hypoglycemia.

The researchers said, "We conclude that translating A1c into eAG produced biased estimates of MBG downloaded from patient glucose meters in low and high HGI patients. However, since MBGI (the difference between eAG and MBG) was positively correlated with HGI, eAG derived using the carefully determined ADAG regression equation may have clinical value for assessing biological variation in A1c. Either HGI or MBGI could prove clinically useful for more comprehensive risk assessment and personalized patient care."

Diabetes Care, published online before print March 31, 2010, doi: 10.2337/dc09-1498