Hemoglobin A1c (glycated hemoglobin)

 

Hemoglobin A1c (glycated hemoglobin) reflects the average blood glucose concentration over the course of the RBC lifespan, roughly 120 days in normal individuals. As the average plasma glucose increases, so does the amount of glycated hemoglobin in the plasma. Limitation of hemoglobin A1c is that it does not provide any indication of the changes in glucose concentrations throughout the day, for which frequent glucose measurements are needed.

The equation to calculate eAG (in mg/dL) from hemoglobin A1c (in %) is as follows: 

eAG (mg/dL) = 28.7 x NGSP-A1c (%) – 46.7

The Diabetes Control and Complications Trial (DCCT) reported that a higher mean A1c level was the dominant predictor of diabetic retinopathy progression. Tighter control shown by levels of HbA1c in the 7% range or lower, were correlated with 35-76% decrease in microvascular complications, like retinopathy, nephropathy and neuropathy, in patients with type 1 diabetes. The extension of DCCT into EDIC study showed benefit in the cardiovascular risk and mortality in the long-term for those patients with lower levels of HbA1c.

 A1c exhibited direct correlations with cholesterol, triglycerides, and LDL and inverse correlation with HDL cholesterol. A1c is identified as a significant risk factor for cardiovascular diseases and stroke in subjects who may have diabetes.

Women with HbA1c 5.7%–6.4% have a significantly higher risk of progression to GDM compared with women with normal HgbA1c values and should be considered for closer GDM surveillance and possible intervention.

ADA Recommendations:

Older adults who are otherwise healthy with few coexisting chronic illnesses and intact cognitive function and functional status should have lower glycemic goals (such as A1C <7.0–7.5%), while those with multiple coexisting chronic illnesses, cognitive impairment, or functional dependence should have less stringent glycemic goals (such as A1C <8.0–8.5%).

Since the lifespan of RBCs is about 120 days, glycated hemoglobin (hemoglobin A1c) represents a measurement of the average blood glucose level over the past 2 to 3 months. Serum proteins are present in the blood for a shorter time, about 14 to 21 days, so glycated proteins, and the fructosamine test, reflect average glucose levels over 2 to 3 weeks.

Instances where fructosamine may be considered over A1c include:

1. Rapid changes in diabetes treatment
2. Diabetic pregnancy
3. Shortened RBC life span, such as hemolytic anemia or blood loss. When the lifespan of RBCs in circulation is shortened, the A1c result is falsely low and is an unreliable measurement of a person's average glucose over time.
4. Abnormal forms of hemoglobin – the presence of some hemoglobin variants, such as hemoglobin S in sickle cell anemia, may affect certain methods for measuring A1c.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends against the use of the A1c test in patients with the hemoglobin variants HbSS, HbSC, or HbCC as these patients may suffer from conditions that affect the A1c test, such as anemia, increased RBC turn-over, and frequent blood transfusions.