Alternative Laboratory Tests for Assessing Blood Glucose Control
Beyond HbA1c, the primary laboratory tests for assessing blood glucose include self-monitoring of blood glucose (SMBG), fasting plasma glucose (FPG), continuous glucose monitoring (CGM), and glycated serum proteins (fructosamine/glycated albumin). 1
Primary Alternative Tests
Self-Monitoring of Blood Glucose (SMBG)
- SMBG provides immediate, hour-to-hour blood glucose measurements that accurately reflect plasma glucose levels when performed properly 1
- SMBG reveals real-time glycemic patterns that HbA1c cannot capture, including postprandial excursions and hypoglycemic episodes 1
- The American Diabetes Association recommends SMBG should be available to providers for use as needed, particularly to supplement information when HbA1c may be unreliable 1
- SMBG is especially valuable for patients on insulin therapy, where evidence supports improved glycemic control with regular monitoring 1
Common pitfall: Plasma glucose values are 10-15% higher than whole blood glucose values, so patients must know whether their monitor reports whole blood or plasma-calibrated results 1
Fasting Plasma Glucose (FPG)
- FPG should be measured in venous plasma after at least 8 hours of fasting 2
- The American Association of Clinical Endocrinologists recommends using tubes containing granulated citrate buffer or placing samples immediately in ice-water slurry and centrifuging within 15-30 minutes to minimize glycolysis 2
- FPG is particularly appropriate when adjusting oral glucose-lowering medications in patients not taking insulin 1
Continuous Glucose Monitoring (CGM)
- CGM can determine 24-hour blood glucose patterns and detect unrecognized hypoglycemia that SMBG misses 1
- The American Diabetes Association notes that continuous ambulatory blood glucose monitoring may be used to identify glucose fluctuations not captured by intermittent testing 1
- CGM measures glucose in interstitial fluid every 5 minutes, providing comprehensive glycemic profiles over 3-6 day periods 3
Alternative Glycated Protein Tests
Fructosamine and Glycated Albumin
- When HbA1c is suspected to be unreliable due to conditions affecting red blood cell lifespan, consider fructosamine or glycated albumin measurements 4
- Glycated serum proteins quantify average glycemia over weeks rather than months, providing a shorter-term assessment than HbA1c 1
- These tests are particularly useful when HbA1c values seem discordant with SMBG results or clinical presentation 4
When to Use Alternative Tests
Situations Where HbA1c May Be Unreliable
- Any condition that slows erythropoiesis or prolongs red blood cell lifespan can falsely elevate HbA1c independent of actual glycemic control 4
- Iron deficiency anemia, which prolongs erythrocyte lifespan, can cause falsely elevated HbA1c 4
- Occult malignancies affecting bone marrow function or chronic infections causing inflammatory responses may alter HbA1c values 4
- When HbA1c is surprisingly high or low, or significantly changed coincident with a change in laboratory method, suspect hemoglobin variant or interference 1
Clinical Decision Algorithm
- For immediate glycemic assessment: Use SMBG or laboratory glucose testing 1
- For 24-hour pattern identification: Use CGM to detect unrecognized hypoglycemia or hyperglycemia 1
- For intermediate-term control (weeks): Use fructosamine or glycated albumin when HbA1c is unreliable 4
- For verification of SMBG accuracy: Compare patient self-testing results with simultaneous laboratory testing 1
Quality Assurance Considerations
- HbA1c testing should only use NGSP-certified methods in accredited laboratories 2
- Glucose measurement should have analytical imprecision ≤2.4%, bias ≤2.1%, and total error ≤6.1% 2
- Sequential HbA1c values within 0.5% do not statistically differ unless the assay coefficient of variation is less than 3% 4
- Point-of-care HbA1c testing is not subject to systematic quality oversight and may be less reliable than laboratory testing 4
Critical Pitfall to Avoid
Relying solely on HbA1c without considering potential confounding factors can lead to inappropriate treatment intensification 4. When HbA1c and SMBG results are discordant, evaluate for conditions affecting red blood cell lifespan (complete blood count, iron studies) and consider alternative glycemic measures 4.