What does an elevated fasting blood glucose (FBS) with a normal glycated hemoglobin (HbA1c) indicate and how should it be evaluated?

High Fasting Blood Sugar with Normal HbA1c

An elevated fasting blood glucose (FBS) with a normal HbA1c most commonly indicates isolated fasting hyperglycemia without sustained post-prandial elevations, but you must rule out conditions that falsely lower HbA1c before accepting this discordance as real.

Understanding the Discordance

The mismatch between high FBS and normal HbA1c reflects fundamentally different measurement windows:

• HbA1c integrates all glucose exposure over 2-3 months, with 50% weighted to the most recent month, 25% to days 30-60 prior, and 25% to days 60-120 prior 1
• A single FBS captures only the basal overnight glucose level and completely misses post-prandial spikes that drive HbA1c 2
• When FBS is elevated but HbA1c remains normal, glucose elevations are likely confined to the fasting period without significant post-meal excursions 2

Conditions That Falsely Lower HbA1c

Before accepting the discordance as real, systematically exclude these confounders:

Red Blood Cell Turnover Disorders

• Hemolytic anemia, recent blood loss, or chronic kidney disease reduce red cell lifespan below 120 days, decreasing glycation time and producing falsely low HbA1c 3
• Hemoglobinopathies (HbS, HbC, HbE) can cause spuriously low or high HbA1c depending on the assay method 1, 3
• Chronic kidney disease causes reduced red cell lifespan, transfusions, and hemolysis that falsely decrease HbA1c 3

Medications and Supplements

• Vitamins C and E inhibit hemoglobin glycation and falsely lower HbA1c 3

Diagnostic Algorithm

Step	Action	Rationale
1. Repeat both tests	Obtain fasting glucose and HbA1c on separate occasions	Rule out pre-analytical error or laboratory variability [2]
2. Obtain CBC with indices	Check hemoglobin, MCV, reticulocyte count	Detect hemolytic anemia or increased red cell turnover [2,3]
3. Check renal function	Measure serum creatinine and eGFR	Advanced CKD (eGFR <30) compromises HbA1c accuracy [3]
4. Consider hemoglobin electrophoresis	Perform if patient is from at-risk ethnic group (African, Mediterranean, Southeast Asian descent)	Identify hemoglobinopathies that interfere with HbA1c assays [2,3]
5. Verify NGSP-certified assay	Confirm laboratory uses standardized HbA1c method	Non-standardized assays produce unreliable results [1,2]
6. Measure post-prandial glucose	Obtain 2-hour post-meal glucose or perform oral glucose tolerance test	Determine if glucose elevations extend beyond fasting period [2]
7. If HbA1c unreliable	Measure glycated albumin (GA)	GA reflects 2-3 weeks of glucose control and is unaffected by red cell disorders [1,2]

When HbA1c is Unreliable: Use Glucose-Based Criteria Only

In these specific conditions, abandon HbA1c entirely and diagnose/monitor using only glucose measurements 3:

• Hemoglobinopathies with altered red cell turnover
• Hemolytic anemia of any cause
• Recent significant blood loss or transfusion
• Advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²)
• Pregnancy (altered red cell turnover)

Alternative Glycemic Markers

Glycated Albumin (GA)

• GA reflects 2-3 weeks of glucose exposure and is superior to HbA1c for capturing short-term changes 1
• Normal reference range in Chinese population: 10.8-17.1% 1
• GA ≥17.1% suggests undiagnosed diabetes and warrants oral glucose tolerance testing 1
• GA is unaffected by red cell disorders, making it ideal when HbA1c is unreliable 1

Continuous Glucose Monitoring (CGM)

• CGM reveals 24-hour glucose patterns including unrecognized nocturnal hypoglycemia and post-prandial spikes 1, 4
• Use CGM when HbA1c and glucose measurements are discordant or when clinical symptoms don't match laboratory values 3, 4

Key Clinical Pitfalls

• Do not assume normal HbA1c excludes diabetes when FBS is elevated—approximately 60% of patients with FBS 126-139 mg/dL have normal HbA1c but may still have excessive glycosylation 5
• Do not diagnose diabetes based solely on FBS 126-139 mg/dL without confirming excessive glycosylation (elevated HbA1c or GA) or abnormal oral glucose tolerance test 5
• Iron deficiency anemia falsely elevates HbA1c (opposite direction), so this does not explain your scenario but must be considered in the differential 3
• African-American individuals have HbA1c values approximately 0.4% higher than white individuals at comparable glucose levels, but this would not explain a low HbA1c 2