Why is fructosamine (a measure of glycated protein) ordered for patients with diabetes, particularly those with conditions affecting red blood cell turnover or requiring tight glucose control?

Why Fructosamine is Ordered

Fructosamine is ordered primarily when HbA1c cannot be reliably measured or interpreted due to conditions affecting red blood cell turnover, such as hemolytic anemia, chronic kidney disease with dialysis, or frequent blood transfusions. 1

Primary Clinical Indications

When HbA1c is Unreliable or Unavailable

• Fructosamine serves as an alternative glycemic marker when HbA1c testing cannot be measured or may not be useful, particularly in hemolytic anemias where shortened red blood cell lifespan falsely lowers HbA1c values 1

• In end-stage kidney disease (ESKD) patients on hemodialysis, HbA1c can be falsely low due to anemia, erythropoietin-stimulating agents, reduced erythrocyte lifespan from uremia, erythrocyte lysis during dialysis, and frequent blood transfusions 1

• Fructosamine measurement is unaffected by red blood cell disorders, making it valuable when discrepancies exist between glucose measurements and HbA1c values 2

Short-Term Glycemic Assessment

• Fructosamine reflects glycemic control over the preceding 2-3 weeks (specifically 1-2 weeks for a single measurement), compared to HbA1c which reflects 2-3 months of glycemia 1

• This shorter timeframe makes fructosamine useful for documenting relatively short-term changes in glycemic status, such as in diabetic pregnancy or after major changes in therapy 1

• The test responds more quickly to changes in therapy than HbA1c, potentially allowing for improved glycemic control adjustments 3

Physiological Basis

• Fructosamine measures total glycated serum proteins (predominantly albumin) through non-enzymatic glycation, forming stable ketoamines 1, 3

• The turnover of human serum albumin has a half-life of 14-20 days, much shorter than hemoglobin's 120-day erythrocyte lifespan, explaining the shorter monitoring window 1, 4

• Fructosamine correlates well with HbA1c and glycated serum albumin measurements in patients without conditions affecting protein metabolism 1

Important Limitations and Caveats

Conditions Affecting Accuracy

• Fructosamine values vary with changes in synthesis or clearance of serum proteins that occur with acute systemic illness or liver disease 1

• In ESKD, fructosamine can be inaccurate due to hypoalbuminemia, which is common in this population 1

• There is ongoing debate about whether fructosamine assays should be corrected for serum protein or albumin concentrations 1

Not Equivalent to HbA1c

• Fructosamine should not be considered equivalent to HbA1c since it only indicates glycemic control over a short period 1

• Unlike HbA1c, fructosamine has not been shown to be related to the risk of development or progression of chronic complications of diabetes 1

• Fructosamine assays would need to be performed monthly to gather the same information as HbA1c measured three to four times per year 1

Clinical Context for Ordering

• The 2024 ADA Standards recommend using alternative approaches to monitoring glycemic status (including fructosamine) in people with conditions that interfere with HbA1c interpretation 1

• Fructosamine may be particularly useful for patients less compliant with home glucose monitoring or where recent changes in insulin dose might not yet be reflected in HbA1c levels 5

• The test is relatively inexpensive, reliable, and simple to perform, making it practical for clinical use 6, 3