What could be the cause of a slightly elevated Hemoglobin A1c (HbA1c) in an adult with low to moderate sugar and carbohydrate intake?

Causes of Elevated HbA1c Despite Low Carbohydrate Intake

Your slightly elevated HbA1c despite controlled carbohydrate intake most likely reflects true hyperglycemia from insulin resistance or early diabetes, but could also be falsely elevated by iron deficiency anemia, occult malignancy affecting bone marrow, chronic infection, or certain medications—all of which prolong red blood cell lifespan and artificially increase HbA1c independent of actual blood sugar levels. 1, 2, 3

Primary Consideration: True Hyperglycemia

The most common explanation is that you have genuine hyperglycemia from type 2 diabetes or prediabetes, where insulin resistance causes elevated blood glucose regardless of dietary carbohydrate restriction. 1

• Type 2 diabetes results from progressive insulin secretory defects combined with insulin resistance, meaning your body cannot effectively use the glucose you consume even with dietary modification 1
• An HbA1c ≥6.5% confirms diabetes diagnosis, while 5.7-6.4% indicates prediabetes 1
• Dietary carbohydrate restriction alone may be insufficient if underlying insulin resistance is severe 4

Conditions That Falsely Elevate HbA1c

Iron Deficiency Anemia

Iron deficiency paradoxically increases HbA1c by prolonging red blood cell lifespan, creating an older erythrocyte population with more accumulated glycation. 1, 2, 3

• Iron-deficient diabetic individuals show HbA1c elevations of approximately 0.5-1.0% compared to iron-sufficient individuals with identical glucose levels 3
• This effect is more pronounced in women (HbA1c 7.02 ± 1.58% vs controls) and those with fasting glucose 100-126 mg/dL 3
• Check complete blood count with red cell indices and ferritin levels to identify this condition 2

Occult Malignancies and Bone Marrow Disorders

Malignancies affecting bone marrow function alter red blood cell production and lifespan, potentially causing falsely elevated HbA1c values. 2

• These conditions create an older red blood cell cohort with prolonged glucose exposure 2
• Consider this if HbA1c seems discordant with self-monitored glucose readings 2

Chronic Infections

Inflammatory responses from chronic infections affect red blood cell turnover, potentially resulting in higher HbA1c than expected based on actual glucose levels. 2

• The inflammatory process can prolong erythrocyte lifespan 2
• Evaluate for occult infections if clinical suspicion exists 2

Medications and Supplements

Certain medications can interfere with HbA1c measurement or alter the glucose-HbA1c relationship. 2

• Hypertriglyceridemia, hyperbilirubinemia, chronic alcoholism, chronic salicylate use, and opiate addiction can falsely increase HbA1c with some assay methods 2
• Vitamins C and E may falsely lower HbA1c by inhibiting hemoglobin glycation 2
• Oral hypoglycemic agents (metformin, sulfonylureas) may alter the glucose-HbA1c relationship 2

Racial and Ethnic Considerations

African Americans may have HbA1c values 0.3-0.4% higher than non-Hispanic whites at identical glucose levels, independent of measured glycemia. 1, 2

• This difference persists even after controlling for clinical and sociodemographic factors 2
• The mechanism remains incompletely understood but should be considered when interpreting results 1

Diagnostic Algorithm

Step 1: Confirm the HbA1c Result

• Repeat HbA1c testing using an NGSP-certified laboratory method to rule out measurement error 1
• Ensure the test was performed using a method standardized to the DCCT assay 1

Step 2: Correlate with Direct Glucose Measurements

Measure fasting plasma glucose and consider 2-hour oral glucose tolerance test to determine if HbA1c accurately reflects your glycemic status. 1, 5

• Fasting glucose ≥126 mg/dL confirms diabetes 1
• 2-hour glucose ≥200 mg/dL during OGTT confirms diabetes 1
• Marked discrepancy between HbA1c and glucose measurements suggests HbA1c interference 1, 5

Step 3: Evaluate for Conditions Affecting Red Blood Cell Turnover

Order complete blood count with red cell indices, ferritin, and peripheral smear to identify conditions that falsely elevate HbA1c. 2, 3

• Check mean corpuscular volume (MCV) for macrocytosis or microcytosis 2
• Measure ferritin to assess iron stores 3
• Review peripheral smear for abnormal red cell morphology 2

Step 4: Consider Alternative Glycemic Monitoring

If conditions affecting red blood cell lifespan are identified, use plasma glucose criteria exclusively for diagnosis and monitoring. 1, 5

• Self-monitoring of blood glucose provides direct measurements unaffected by RBC turnover 5, 2
• Fructosamine or glycated albumin reflect 2-4 weeks of glycemic control and are unaffected by red cell issues 5, 2
• Continuous glucose monitoring offers comprehensive assessment when available 5, 2

Critical Pitfalls to Avoid

Do not dismiss an elevated HbA1c as solely due to dietary factors without investigating for true hyperglycemia or interfering conditions. 1, 2

• Relying on HbA1c alone when interfering conditions exist will either overestimate or underestimate true glycemic burden 2
• Treatment decisions based solely on a single HbA1c without considering other clinical data may lead to inappropriate therapy 2
• Sequential HbA1c values within 0.5% do not statistically differ unless assay coefficient of variation is <3% 2

Ensure adequate carbohydrate intake (at least 150 g/day) for 3 days prior to oral glucose tolerance testing, as very low carbohydrate diets can cause falsely abnormal results. 1