In a 50-year-old woman with rheumatoid arthritis treated with adalimumab (Humira), normal BMI and active lifestyle, who has an elevated hemoglobin A1c of 7.8% with a fasting glucose of 80 mg/dL and fasting insulin of 6.5 µU/mL, should we perform a workup for type 1 diabetes mellitus or simply repeat the A1c?

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Last updated: September 17, 2026 • View editorial policy

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Repeat the A1C and Confirm with Fasting Glucose—Type 1 Diabetes Workup is Not Indicated at This Time

Given the marked discordance between your patient's elevated A1C (7.8%) and normal fasting glucose (80 mg/dL) with normal fasting insulin (6.5 µU/mL), you should repeat the A1C using a certified assay and confirm with fasting glucose or an oral glucose tolerance test before pursuing any diabetes workup, including type 1 diabetes testing. This discordance strongly suggests either assay interference or a condition altering the A1C-glycemia relationship rather than true diabetes 1, 2.

Why This Discordance Matters

The current guidelines are clear: when there is marked discordance between A1C and plasma glucose levels, this should raise suspicion for A1C assay interference 2. Your patient's clinical picture—normal BMI, active lifestyle, normal fasting glucose (80 mg/dL), and appropriate fasting insulin (6.5 µU/mL)—does not support diabetes of any type. The A1C of 7.8% would typically correspond to average glucose levels around 180 mg/dL, which is completely inconsistent with her fasting glucose of 80 mg/dL.

Specific Conditions to Consider in RA Patients on Humira

Several factors in your patient warrant consideration:

  • Chronic inflammation from RA: Inflammatory conditions can alter erythrocyte turnover and affect the A1C-glycemia relationship 3, 4. RA patients have altered metabolic pathways primarily due to chronic inflammation, which can affect hemoglobin glycation independently of true glycemia.

  • Adalimumab (Humira) effects: While the FDA label doesn't specifically mention A1C interference, biologic therapies can modulate inflammatory markers that may indirectly affect A1C reliability 5.

  • Assay interference: Recent case reports demonstrate that A1C values can be spuriously elevated due to analytical interference, with rapid normalization upon repeat testing 6.

Recommended Diagnostic Algorithm

Step 1: Repeat A1C immediately

  • Use an NGSP-certified method standardized to the DCCT assay 1, 2
  • If possible, use a different laboratory or assay method to rule out interference

Step 2: Obtain confirmatory glucose testing

  • Fasting plasma glucose on the same day as repeat A1C
  • Consider a 2-hour oral glucose tolerance test (OGTT), which is more sensitive and accurate when there is A1C-glucose discordance 2

Step 3: Interpret results

  • If repeat A1C remains elevated (≥6.5%) BUT fasting glucose remains normal (<100 mg/dL) and OGTT is normal, do not diagnose diabetes
  • Per guidelines, in conditions with altered A1C-glycemia relationships, only plasma glucose criteria should be used for diagnosis 2

Why Type 1 Diabetes Workup is Premature

Type 1 diabetes workup (autoantibodies: GAD65, IA-2, ZnT8, insulin autoantibodies) is not indicated at this point because:

  1. No hyperglycemia documented: Your patient has normal fasting glucose and normal insulin levels, which argue strongly against any form of diabetes
  2. Wrong age demographic: New-onset type 1 diabetes at age 50 is uncommon (though not impossible as latent autoimmune diabetes in adults/LADA)
  3. No clinical symptoms: Type 1 diabetes typically presents with symptomatic hyperglycemia 2
  4. Diagnosis requires confirmed hyperglycemia first: Per ADA guidelines, diabetes diagnosis must be established by demonstrating hyperglycemia before subtyping 1, 2

Common Pitfalls to Avoid

  • Do not initiate diabetes treatment based on a single discordant A1C value
  • Do not order diabetes autoantibodies until you've confirmed actual hyperglycemia with glucose measurements
  • Do not assume the A1C is accurate when it contradicts clinical presentation and glucose values—this is a red flag for interference 2, 6, 4

If Repeat Testing Confirms Discordance

Should the repeat A1C remain elevated with persistently normal glucose values, consider:

  • Hemoglobin electrophoresis to rule out hemoglobinopathies (though these typically lower A1C)
  • Complete blood count to assess for anemia or altered RBC turnover
  • Inflammatory markers (CRP, ESR) to quantify current RA disease activity
  • Using only glucose-based criteria for any future diabetes diagnosis in this patient 2

The bottom line: This patient almost certainly does not have diabetes of any type. The discordant A1C likely reflects assay interference or inflammation-related alterations in hemoglobin glycation. Confirm with repeat testing before any further workup.

References

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