What is being tested?

The fructosamine test is a measurement of glycated protein which is formed by a nonenzymatic reaction of serum proteins with glucose. However, glycated albumin (GA) is the major component of fructosamine because albumin represents 60-80% of the total protein in the plasma.. When glucose levels in the blood are elevated over a period of time, glucose molecules permanently combine with haemoglobin found inside the red blood cells (RBCs) and with albumin and other serum proteins like lipoproteins and globulins - a process called glycation. The more glucose that is present, the greater the amount of glycated haemoglobin and glycated protein formed.

The term “fructosamine” is derived from the 5-atom ring formed when serum proteins are glycated that is reminiscent of fructose. However other than this structural similarity, fructosamine is not related to fructose or fructose metabolism.

These combined molecules persist for the life of the RBC or the protein and provide a record of the average amount of glucose that has been present in the blood over that time period. Since RBCs live for about 120 days, glycated haemoglobin (HbA1c) reveals average blood glucose levels over the past 2 to 3 months. Serum proteins have a shorter lifespan, about 14 to 21 days, so glycated proteins reflect average glucose levels over a 2 to 3 week time period. Glycated Albumin (GA) is also another marker which specifically looks at glycation of albumin where as fructosamine reflects the total concentration of glycated serum proteins

Keeping blood glucose levels as close as possible to normal allows diabetic patients to avoid many of the complications and progressive damage associated with elevated glucose levels. Good diabetic control is achieved and maintained by daily (or even more frequent) self-monitoring of glucose levels and by occasional monitoring of the effectiveness of treatment using either a fructosamine or HbA1c test.

How is it used?

Fructosamine testing has been available since the 1980s. Both fructosamine and HbA1c tests are used primarily as monitoring tools to help diabetics control their blood sugar (glucose), but HbA1c is much more popular and more widely accepted. Fructosamine may be useful in situations where the HbA1c cannot be reliably measured. Instances where fructosamine may be a better monitoring choice than HbA1c include:

• Assessment of short-term/ rapidly changing  - fructosamine allows the effectiveness of diet or medication adjustments to be evaluated after a couple of weeks rather than months
• Diabetic pregnancy - good control is essential during pregnancy and the needs of the mother frequently change during gestation; fructosamine measurements may be ordered along with glucose levels to help monitor and accommodate shifting glucose and insulin requirements
• Shortened RBC life span - an HbA1c test will not be accurate when a patient has a condition that affects the average age of red blood cells (RBCs) present, such as haemolytic anaemia or blood loss. . Certain haemoglobinopathies (e.g. HbSS, HbSC, HbCC, thalassemia, etc.) are associated with haemolysis as well.
• Abnormal forms of haemoglobin.The presence of some haemoglobin variants may affect certain methods for measuring HbA1c such as hemoglobin S in sickle cell anaemia or may even reduce beta-chain glycation even in the absence of anaemia (e.g. Hb Raleigh).. In these cases, fructosamine can be used to monitor glucose control.
• Renal disease - the anaemias associated with chronic kidney disease (CKD) are usually accompanied by increased red cell turnover. Patients with CKD are frequently treated with iron and/or erythropoietin therapy or blood transfusion, so that the measurement of HbA1c might be unreliable. HbA1c levels underestimates glycaemic control in diabetic haemodialysis patients, whereas fructosamine more accurately reflects glucose homeostasis.

Since the fructosamine concentrations of well-controlled diabetics may overlap with those of non-diabetics, the fructosamine test is not useful as a screen for diabetes.

However, it must be noted that there are no outcome data to show what the consequence is on the development of diabetic complications for any particular level of fructosamine. In contrast, HbA1c has firm data to show chronically elevated A1c level predicts an increased risk for certain diabetic complications, such as problems with the eyes (diabetic retinopathy), possibly leading to blindness, kidney disease (diabetic nephropathy), and nerve damage (diabetic neuropathy).

Conditions where fructosamine might be unreliable are:

• Abnormal plasma proteins (e.g., IgA myeloma),
• Hypoproteinemia
• Increased plasma protein metabolism or loss e.g. liver disease, nephrotic syndrome

The above factors affect the fructosamine level independent of glycemia. Therefore, just as with Hb A1c measurements, fructosamine (or GA) measurements must be interpreted with care.

When is it requested?

To help monitor your blood glucose (sugar) levels over time if you have diabetes mellitus, especially if it is not possible to monitor your diabetes using the A1c test; to help determine the effectiveness of changes to your diabetic treatment plan that might include changes in diet, exercise or medications, especially if they were made recently. It monitors a patient's average glucose over the past 2 to 3 weeks. Fructosamine levels also may be ordered when a diabetic patient is pregnant.

What does the result mean?

If a patient's fructosamine is increased, then the patient's average glucose over the last 2 to 3 weeks has been elevated. In general, the higher the fructosamine concentration the higher the average blood glucose level. Trends may be more important that absolute values. If there is a trend from a normal to high fructosamine, it may indicate that a patient's glucose control is not adequate - that they are getting too much sugar, too little insulin, or that their insulin treatment has become less effective.

Normal fructosamine levels may indicate that a patient is either not diabetic (and therefore should not be monitored) or that they have good diabetic control. A trend from high to normal fructosamine levels may indicate that changes to a patient's treatment regimen are effective.

Fructosamine results must be evaluated in the context of the patient's total clinical findings. Falsely low fructosamine results may be seen with decreased protein/or albumin levels, conditions associated with increased protein loss in the urine or gastrointestinal tract, or a change in the type of protein produced by the body. In this case, a discrepancy between the results obtained from daily glucose monitoring and fructosamine testing may be noticed. Also, someone whose glucose concentrations swing erratically from high to low may have normal or near normal fructosamine and HbA1c levels but still have a condition that requires frequent monitoring.

The advantage of glycated albumin compared to fructosamine is that glycated albumin can be expressed as the ratio of GA to total albumin, thus minimizing the interference due to the concentrations of glycated and non-glycated albumin. The current method for measuring glycated albumin is also better standardized and less susceptible to preanalytical variables than fructosamine.

However, it must be noted that there are no outcome data to show what the consequence is on the development of diabetic complications for any particular level of fructosamine.

Common questions

• Do I need to fast for a fructosamine test?

No. Since it measures glycated protein and determines the average glucose over the past 2-3 weeks, the test is not affected by food that you have eaten during the day. For the same reason, fructosamine can be measured at any time during the day.

• Should someone with a family history of diabetes have a fructosamine and an HbA1c test?

Not usually. These tests are not recommended for screening non-diabetic patients, even if you have a strong family history. One or more may be ordered, however, if you have an elevated fasting glucose.

More information

RCPA Manual: Fructosamine