Hemoglobin (Hb) is the compound in the red blood cells that transports oxygen. One of the types of hemoglobin (Hb) is called HbA; HbA1c is a specific subtype of HbA. Glucose binds slowly to Hb and produces glycosylated Hb. There are several types of glycosylated hemoglobin measures (including total glycosylated Hb and HbA1), but HbA1c, which is formed when HbA is glycosylated, is now considered the best and standard measure.
The higher the blood sugar, the faster HbA1c will be formed, resulting in higher HbA1c levels. Red blood cells circulate 60-120 days, and the HbA1c level is in part affected by blood sugar levels over a three-month period. However, it is heavily weighted to levels over the past 45-60 days.
It is a simple way to evaluate average glucose levels over the past two to four weeks.
It is the best single test for evaluating the risk for glycemic damage to tissues (e.g., nerves, and small blood vessels in the eyes and kidneys) and, thus, risk of complications of diabetes.
Clinical trials, such as the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have shown that improving HbA1c measures will decrease the development and progression of eye, kidney and nerve complications in both type 1 and type 2 diabetes.
The HbA1c is linearly related to the average blood sugar over the past 1-3 months (but is somewhat weighted to the past 2-4 weeks).
The HbA1c is strongly associated with the risk of development and progression of microvascular and nerve complications.
Since these complications occur slowly over time, the younger you are when you get diabetes (or the longer your life expectancy), the higher the risk of end-stage complications.
High HbA1c (>9.0-9.5%) is associated with very rapid progression of microvascular complications.
Additional information on interpretation of HbA1c values and recommendations can be found in "Clinical Practice Recommendations 2002" of the American Diabetes Association (Diabetes Care Vol 25; Suppl 1; pp S35-S37, 2002).
What are the different HbA1c assays used at the University of Michigan (U-M)?
What are the differences, advantages and disadvantages of the HPLC versus immuno-turbidimetric HbA1c assays?
The assays should achieve very similar values and are both calibrated to the DCCT standard. Upper limits of normal for all HbA1c assays is about 6.2 but can vary slightly between specific machines.
What are total glycosylated hemoglobin and HbA1?
HbA1c is just one type of glycosylated hemoglobin. The HbA1 measure includes all types of glycosylated HbA (including HbA1c) and total glycosylated hemoglobin includes virtually all types of hemoglobin affected by blood sugar level. Based upon analyses of 225 split sample specimens run by the CIC between April and October of 2000, conversion formulas between HbA1c and TGHb were calculated. The correlation between the two measures was excellent (0.966), however, assays can vary from laboratory to laboratory, so it should not be assumed that the formulas given below can be generalized to other laboratories.
It is recommended that HbA1c be used for all patient care and for newly-initiated research, since this is the assay used in the DCCT and most other clinical trials.
HbA1 tends to run roughly one point higher than HbA1c (an estimate of HbA1c can be made using the formula HbA1c = 0.9HbA1 + 0.05).
TGHb = (1.325 * HbA1c) - 0.803.
Although it is recommended that the HbA1c assay be used in all newly-initiated studies, continued use of the TGHb assay is recommended for ongoing studies that have already been using this assay.
All statistical analyses should be conducted using the measured TGHb values.
Presentation of study results should also include the calculated HbA1c estimates using the above conversion formulas.
The diversity of assay methods (e.g., HPLC, Immune-based assays, Mass spectrometry, Capillary electrophoresis), instruments, calibration approaches and standards have traditionally posed potential difficulties and inaccuracies in comparing results from measurements of glycated hemoglobins.
The National Glycohaemoglobin Standardization Program, based on the HPLC reference method of the Diabetes Control and Complications Trial for the measurement of HbA1c, has developed a program to provide traceability to the DCCT measurements through a national reference laboratory network. This program also has allowed laboratories and commercial manufacturers to develop traceability of their assays and results to the DCCT standards. The NGSP's efforts have resulted in a much-improved ability to compare Glycohaemoglobin results obtained through different assays and instruments.