Diabetes Lab Testing: Hemoglobin A1c vs. Fructosamine
Hemoglobin A1c is a reflection of your blood sugar over the past 2 to 3 months. Hemoglobin is the iron-containing oxygen transport protein in red blood cells. Ninety-seven percent of normal hemoglobin is made up of four protein chains. A small fraction of the remaining 3 percent is made up of a hemoglobin component called A1c. The rate of A1c formation is directly related to the average concentration of glucose. Thus, when your blood sugars are higher, there is more A1c formed, making it an excellent marker of glycemic control. Since your body makes a whole new set of red blood cells every 120 days, this test is able to provide you with an estimate of your blood sugar over that time frame. If you have diabetes, you’ve likely been told to aim for an HbA1c of less than 7 percent. For people without diabetes, we expect this level to be less than 5.7 percent. Higher HbA1c levels represent higher average blood sugar over a three-month time period.
While HbA1c is considered the gold standard for the diagnosis of diabetes and the assessment of glycemic control, there are numerous conditions that impact its clinical relevance. Conditions that change the life span of red blood cells directly impact the accuracy of HbA1c results. This could include a recent blood loss, pregnancy, sickle cell, use of erythropoietin, kidney failure, hemodialysis, a blood transfusion, iron-deficiency anemia, alcohol use disorder, or liver disease. In addition, if you’re of African, Mediterranean, or Southeast Asian descent or have family members with sickle cell anemia or thalassemia, an HbA1c test could be unreliable for diagnosing or monitoring glycemia (NIDDK [National Institute of Diabetes and Digestive and Kidney Diseases] 2018). Some people from these regions have a hemoglobin variant that can interfere with some HbA1c tests. Most people with a hemoglobin variant have no symptoms and may not know that they carry this type of hemoglobin.
If your HbA1c and blood glucose results don’t quite add up, you have one of the conditions mentioned above, or think you may have a hemoglobin variant based on your ethnic background, you might want to ask your health practitioner to do further testing. Testing fructosamine instead of HbA1c or using a CGM could provide a more accurate picture of your state of glucose control.
Fructosamine is a glycated protein formed when blood glucose binds to serum proteins, predominantly albumin. Since the lifespan of albumin is just two to three weeks, fructosamine reflects a person’s average blood sugar level over two to three weeks. Since it doesn’t use hemoglobin to estimate the average glucose level, this test is preferred in certain situations, such as pregnancy, when hemoglobin levels are out of range or in the case of certain blood disorders, such as sickle cell or other hemoglobin variations. In addition, this test may be helpful in assessing more recent blood sugar changes, since it reflects weeks rather than the months that the HbA1c reflects. A fructosamine value of 285 mmol/L correlates to a HbA1c of 6.5%, the HbA1c value that is diagnostic of diabetes. The chart below provides information that can be used to interpret fructosamine results.
However, fructosamine interpretation may be unreliable when conditions such as nephrotic syndrome, liver disease, thyroid disease, Celiac disease, or Berger disease are present. In addition, high intake of Vitamin C (ascorbic acid) can interfere with the reliability of the test, so supplements should be ingested for 24 hours before testing.
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References:
Cohen RM, Holmes YR, Chenier TC, & Joiner CH. Discordance Between HbA1c and Fructosamine: Evidence for a glycosylation gap and its relation to diabetic nephropathy. Diabetes Care. 2003 Jan 1; 26 (1): 163–167.
Nansseu JRN, Fokom-Domgue J, Noubiap JJN, et al. Fructosamine measurement for diabetes mellitus diagnosis and monitoring: a systematic review and meta-analysis protocol. BMJ Open. 2015 ;5:e007689.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “The A1C Test & Diabetes.” NIDDK.com. Last reviewed April 2018. https://www.niddk.nih.gov/health-information/diagnostic-tests/a1c-test.
Ribeiro RT, Macedo MP, Raposo JF, et. al. HbA1c, Fructosamine, and Glycated Albumin in the Detection of Dysglycaemic Conditions. Current Diabetes Reviews. 2016 Mar 1.