The Limitations Of Hemoglobin A1c

When assessing glycemic control in the majority of our applicants, hemoglobin A1c is the gold standard for assessing glucose control over an intermediate period of time. It controlled for many of the “I had a bad diet yesterday,” “It was a tough weekend,” or “Except for last week I ate perfectly.” Yet there are circumstances when hemoglobin A1c may be an unreliable value. As such, there are other ways of getting a fair picture of glucose control.

Hemoglobin itself is the molecule within red blood cells that carries oxygen to the body tissues. A small part of the hemoglobin has sugar attached to it, and this is measured as the hemoglobin A1c. The amount of hemoglobin A1c is dependent on the level of sugar in the blood—higher sugar levels mean higher hemoglobin A1cs. As the red blood cell in the body has a life of about 120 days, a blood measurement may find a red cell that is 119 days old or one that may be a day or two old. That average in-between (of approximately 8 weeks) correlates to the hemoglobin A1c.

A random blood sugar is truly the measurement only at the exact time the blood is drawn, and represents a moment in time. Sugar in the urine sample may or may not correlate to the degree of glucose control in the body at a given moment. Fructosamine, also used by our testing labs, measures average glucose in the two to three week range. In clinical practice, a doctor uses random blood sugars, fasting bloods and a short term measure of control (such as fructosamine) to guide medication therapy. For insurance purposes, hemoglobin A1c provides a much better guide to intermediate and longer term control and allows assessment of the effectiveness of blood sugar control that excuses a day or even a week or two of non-compliance.

Many conditions that modify red blood cell production, destruction or influence the life span of the red cell will alter A1c measurements. Those include chronic renal disease (with shortened red cell life) that may decrease the A1c level, chronic liver disease (which may increase or decrease the level), and the absence of a spleen, where there is decreased red cell turnover due to an increased red blood cell life span (as there is no spleen to serve as a filter for removing abnormal or old cells). Iron deficiency anemia increases hemoglobin A1c as a reduced red blood cell turnover prolongs the survival of the cells. Hemolytic anemia does the opposite with reduced RBC turnover prolonging RBC survival. And all bets are off in pregnancy, where hemoglobin A1c may be increased later in the pregnancy but decreased early on.

Sometimes people with different hemoglobins can have completely different A1c measurements. Sickle cell anemia, thalassemia and many variants found in ethnic populations can provide strikingly different results that have little if anything to do with the degree of sugar control. The results are multifactorial and can depend on the type of hemoglobinopathy and/or anemia that exists. Even simple Vitamin B12 and folate deficiencies in the diet may increase hemoglobin A1c by reducing the turnover of cells and prolonging the red blood cell survival.

When hemoglobin A1c values are off and don’t correlate to the true clinical picture in an applicant or patient, there are other tests used to get a more accurate picture. Serum fructosamine (as mentioned previously) is a circulating glycated protein (mostly albumin) that is independent of hemoglobin abnormalities. It is more related to the half-life of albumin (about 17-20 days) and as such gives a very accurate but shorter period of control measurement of two to three weeks. Glycated albumin also gives a good 14-21 day measure of glycemic control but has limitations in those with any albumin problem (like liver disease or thyroid dysfunction). Capillary blood glucose and continuous blood glucose monitoring are both quite effective but generally limited to clinical practice in those who have an established diabetes diagnosis and are assessing the degree of control diet and medication may bring.

As insurance laboratory blood testing can now run both fructosamine and hemoglobin A1c on the same sample, there are less problems with assessment of glucose control that an underlying blood abnormality may disguise. Severe conditions in body physiology and disease are usually quite obvious (like kidney or liver failure) by other clinical and laboratory testing and can differentiate a hemoglobin A1c abnormality quickly. Thankfully though the measures used now in our laboratory assessment of blood sugar control provide us an accurate means for an underwritable situation and accurate assessment of blood sugar control.

MD, FACE, FLMI, board certified internist and endocrinologist, is medical director for SBLI of Massachusetts. He has extensive brokerage and life insurance experience over 30 years with Pacific Life, MetLife Brokerage and Transamerica Occidental Life.

Goldstone is board certified in insurance medicine and the inaugural recipient of the W. John Elder Award for Insurance Medicine Journalism Excellence. He was also honored as a fellow of the prestigious American College of Endocrinology and has written monthly for Broker World from 1991 to September, 2021.

Goldstone can be reached by ­telephone at 949-943-2310. Emaill: