In a 68‑year‑old asymptomatic patient with an HbA1c of 12.1 % and fasting plasma glucose of 103 mg/dL and random blood glucose of 101 mg/dL, what is the appropriate diagnosis and which additional investigations should be performed?

Diagnosis: Diabetes Mellitus

This 68-year-old patient has diabetes mellitus based on an HbA1c of 12.1%, which far exceeds the diagnostic threshold of ≥6.5%. 1, 2 The fasting and random glucose values of 103 and 101 mg/dL are paradoxically normal, creating a marked discordance that requires investigation before finalizing management.

Diagnostic Confirmation

• The HbA1c of 12.1% alone is sufficient to diagnose diabetes, but the striking discordance with normal glucose values mandates repeat testing to exclude laboratory error or conditions that falsely elevate HbA1c. 1, 3

• Repeat the HbA1c measurement in a certified NGSP laboratory on a separate sample; if the second result is also ≥6.5%, diabetes is definitively confirmed. 1, 2

• Simultaneously obtain a fasting plasma glucose (≥8 hours fasting) on the same day as the repeat HbA1c; if fasting glucose is ≥126 mg/dL, diabetes is confirmed by two different tests without further testing needed. 1, 3

Essential Additional Investigations

Rule Out Conditions That Falsely Elevate HbA1c

• Order a complete blood count (CBC) with red blood cell indices to screen for anemia, which can spuriously increase HbA1c independent of glycemia. 4, 5 Iron-deficiency anemia in particular raises HbA1c relative to actual glucose exposure. 4

• Obtain serum iron studies (ferritin, transferrin saturation) to detect iron deficiency, which invalidates HbA1c as a diagnostic tool. 4

• Screen for hemoglobinopathies (hemoglobin electrophoresis or high-performance liquid chromatography) if the patient is of African, Mediterranean, or Southeast Asian ancestry, as HbS, HbC, and other variants interfere with HbA1c assays. 4, 2

• Review the patient's medication list and recent medical history for conditions that alter red-cell turnover: recent blood transfusion, erythropoietin therapy, hemodialysis, or hemolytic anemia—all of which render HbA1c unreliable. 4, 2

• If any of these conditions are present, disregard the HbA1c entirely and diagnose diabetes using only plasma glucose criteria (fasting ≥126 mg/dL or 2-hour OGTT ≥200 mg/dL). 4, 2

Baseline Metabolic and Cardiovascular Assessment

• Obtain a comprehensive metabolic panel including serum creatinine and calculate estimated glomerular filtration rate (eGFR) before initiating metformin, which is contraindicated when eGFR <30 mL/min/1.73 m². 3

• Measure urine albumin-to-creatinine ratio (UACR) to screen for diabetic kidney disease at diagnosis. 3

• Order a fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess cardiovascular risk, which is equivalent to that of a patient with prior myocardial infarction. 3

Clarify Glycemic Status with Oral Glucose Tolerance Test

• Perform a 75-gram oral glucose tolerance test (OGTT) to resolve the discordance between HbA1c and fasting/random glucose; a 2-hour value ≥200 mg/dL confirms diabetes. 1, 2

• Ensure the patient consumes at least 150 grams of carbohydrate daily for three days before the OGTT; fasting or carbohydrate restriction falsely elevates glucose during the test. 4, 3

• Centrifuge and separate plasma immediately after blood collection to prevent glycolysis-induced falsely low glucose values. 4, 3

Interpretation of the Discordance

• An HbA1c of 12.1% typically reflects an average plasma glucose of approximately 300 mg/dL over the preceding 2–3 months, yet the patient's fasting and random glucose are normal—this degree of mismatch is highly unusual and suggests either laboratory error, assay interference, or a condition affecting red-cell turnover. 4, 6

• African Americans and certain other ethnic groups may have HbA1c values 0.3–0.4% higher than non-Hispanic Whites at the same glucose levels, but this does not explain a 12.1% HbA1c with normal glucose. 4

• If hemoglobinopathy or anemia is confirmed, the HbA1c is invalid; rely exclusively on fasting glucose ≥126 mg/dL or 2-hour OGTT ≥200 mg/dL to diagnose diabetes. 4, 2

Common Pitfalls to Avoid

• Do not diagnose diabetes based solely on a single HbA1c value when marked discordance with glucose measurements exists; always repeat testing and investigate for assay interference. 4, 2

• Do not use point-of-care HbA1c devices for diagnosis; only NGSP-certified laboratory methods standardized to the DCCT assay are acceptable. 1, 3

• Do not assume the patient is asymptomatic without specifically asking about polyuria, polydipsia, unexplained weight loss, blurred vision, and recurrent infections—these symptoms may be subtle or attributed to aging. 1, 3

• Do not delay confirmatory testing; the American Diabetes Association recommends performing the second test promptly rather than waiting weeks or months. 3