Laboratory Tests for Diabetes Monitoring
Core Laboratory Tests
- The American Diabetes Association recommends measuring hemoglobin A1c (HbA1c), fasting plasma glucose, and urine albumin-to-creatinine ratio regularly to assess glycemic control and screen for complications 1, 2
- HbA1c should be measured routinely every 3 months until acceptable targets are reached, then at least every 6 months to assess long-term glycemic control, as recommended by the American College of Endocrinology 3
- Fasting Plasma Glucose (FPG) should be measured in venous plasma, with samples collected after at least 8 hours of fasting, according to the American Association of Clinical Endocrinologists 4
- To minimize glycolysis in FPG samples, the American Association of Clinical Endocrinologists recommends using tubes containing granulated citrate buffer or placing the sample immediately in ice-water slurry and centrifuging within 15-30 minutes 4
Kidney Function Monitoring
- The National Kidney Foundation recommends measuring Urine Albumin-to-Creatinine Ratio (uACR) annually in all adults with diabetes using morning spot urine samples, with a strength of evidence rated as high 2
- First morning void urine samples are preferred for uACR measurement to minimize variability, as suggested by the American Diabetes Association 2
- More frequent uACR testing (every 6 months) is needed if estimated glomerular filtration rate is <60 mL/min/1.73 m² and/or albuminuria is >30 mg/g creatinine, according to the National Kidney Foundation 2
Timing of Laboratory Tests
- For type 1 diabetes, the American Diabetes Association recommends using plasma glucose rather than HbA1c for diagnosis in individuals with symptoms of hyperglycemia, with a strength of evidence rated as moderate 5
- For type 2 diabetes, the American Association of Clinical Endocrinologists recommends using HbA1c ≥6.5% (≥48 mmol/mol) for diagnosis, with a strength of evidence rated as high 3
Special Considerations
- The American Diabetes Association recommends measuring C-peptide to help distinguish type 1 from type 2 diabetes in ambiguous cases, such as individuals with type 2 phenotype who present in ketoacidosis, with a strength of evidence rated as low 2
- For insulin pump therapy coverage, the American Association of Clinical Endocrinologists recommends measuring fasting C-peptide when simultaneous fasting plasma glucose is <220 mg/dL, with a strength of evidence rated as moderate 2
Quality Assurance Considerations
- The American College of Endocrinology recommends that HbA1c testing should only use NGSP-certified methods in accredited laboratories, with a strength of evidence rated as high 3
- The National Kidney Foundation recommends analytical performance goals for urine albumin measurement: between-day precision ≤6%, bias ≤7% to 13%, and total allowable error ≤24% to 30%, with a strength of evidence rated as moderate 2
- The American Association of Clinical Endocrinologists recommends that glucose measurement should have analytical imprecision ≤2.4%, bias ≤2.1%, and total error ≤6.1%, with a strength of evidence rated as high 4
Assessing Blood Glucose Control Beyond HbA1c
Primary Alternative Tests
- Self-monitoring of blood glucose (SMBG) provides immediate, hour-to-hour blood glucose measurements that accurately reflect plasma glucose levels when performed properly, and is especially valuable for patients on insulin therapy, according to the American Diabetes Association, with evidence supporting improved glycemic control with regular monitoring 6, 7
- SMBG reveals real-time glycemic patterns that HbA1c cannot capture, including postprandial excursions and hypoglycemic episodes, and should be available to providers for use as needed, particularly to supplement information when HbA1c may be unreliable 8, 9, 10
- The American Diabetes Association recommends using SMBG to identify glucose fluctuations not captured by intermittent testing, and notes that continuous ambulatory blood glucose monitoring may be used to identify glucose fluctuations not captured by intermittent testing 9, 10
Alternative Glycated Protein Tests
- Glycated serum proteins, such as fructosamine or glycated albumin, quantify average glycemia over weeks rather than months, providing a shorter-term assessment than HbA1c, and are particularly useful when HbA1c values seem discordant with SMBG results or clinical presentation 9, 10, 11
Clinical Decision Algorithm
- For immediate glycemic assessment, the American Diabetes Association recommends using SMBG or laboratory glucose testing, and for 24-hour pattern identification, using CGM to detect unrecognized hypoglycemia or hyperglycemia 9, 10, 11
- For verification of SMBG accuracy, the American Diabetes Association recommends comparing patient self-testing results with simultaneous laboratory testing 9, 10
Potential Confounding Factors
- Any condition that slows erythropoiesis or prolongs red blood cell lifespan can falsely elevate HbA1c independent of actual glycemic control, and when HbA1c is surprisingly high or low, or significantly changed coincident with a change in laboratory method, suspect hemoglobin variant or interference 12, 13