In a 68‑year‑old man with glycated hemoglobin (HbA1c) 12.1 % but fasting blood glucose (FBG) 101 mg/dL and random blood glucose (RBG) 103 mg/dL, what diabetes classification/stage does he fall into and what baseline investigations are recommended?

Diabetes Classification and Baseline Investigations

Diagnostic Discordance Requires Immediate Confirmation

This patient has a markedly discordant presentation—HbA1c 12.1% (indicating severe chronic hyperglycemia) versus normal fasting and random glucose values (101 and 103 mg/dL)—which mandates repeat testing before any diabetes classification or treatment decision. 1, 2

The HbA1c of 12.1% far exceeds the diagnostic threshold of ≥6.5% and would typically correspond to a mean plasma glucose of approximately 298 mg/dL, yet the measured glucose values are completely normal. 1 This degree of discordance strongly suggests either laboratory error or conditions affecting HbA1c measurement accuracy. 3

Immediate Repeat Testing Protocol

Repeat both HbA1c and fasting plasma glucose within days (not weeks or months) using:

• HbA1c: Use a boronate affinity method rather than immunoassay or ion-exchange chromatography, as boronate affinity methods are less susceptible to interference from hemoglobin variants and other structural abnormalities. 3
• Fasting glucose: Ensure a true 8-hour overnight fast with no caloric intake, performed in a certified laboratory (never point-of-care). 2
• Same-day testing: Obtain both tests simultaneously to allow immediate diagnostic clarification if both are abnormal. 2

Conditions That Falsely Alter HbA1c

Factors That Falsely Lower HbA1c (Despite True Hyperglycemia):

• Shortened red blood cell lifespan: Recent blood loss, hemolytic anemia, chronic kidney disease, or pregnancy. 3
• Hemoglobin variants: HbS (sickle cell trait), HbC, HbE—depending on the specific assay method used. 3, 4
• Medications: High-dose vitamin C or E supplementation. 3

Factors That Falsely Elevate HbA1c (Without True Hyperglycemia):

• Iron deficiency anemia: Prolongs erythrocyte lifespan, exposing cells to glucose for longer periods. 3
• Occult malignancy: Bone marrow dysfunction alters red blood cell production and lifespan. 3
• Chronic infection or inflammation: May increase red blood cell turnover in unpredictable ways. 3
• Hypertriglyceridemia, hyperbilirubinemia, chronic alcoholism, or opiate use: Can interfere with certain assay methods. 3

Diagnostic Algorithm Based on Repeat Results

Repeat HbA1c	Repeat Fasting Glucose	Interpretation	Next Steps
≥6.5%	≥126 mg/dL	Diabetes confirmed	Proceed to baseline investigations below
≥6.5%	100–125 mg/dL	Diabetes confirmed (HbA1c criterion met)	Investigate causes of glucose-HbA1c discordance; order hemoglobin electrophoresis, CBC with iron studies
5.7–6.4%	100–125 mg/dL	Prediabetes	Intensive lifestyle intervention; annual monitoring
<5.7%	<100 mg/dL	Normal	Original HbA1c was laboratory error; rescreen in 3 years

1, 2, 5

Baseline Investigations Once Diabetes Is Confirmed

1. Assess for Acute Diabetic Emergencies

• Serum β-hydroxybutyrate, venous pH, bicarbonate: Rule out diabetic ketoacidosis (DKA), especially given the magnitude of HbA1c if confirmed. 5
• Serum osmolality, sodium, BUN, creatinine: Rule out hyperosmolar hyperglycemic state (HHS). 5
• Electrolytes (potassium, phosphate, magnesium): Severe hyperglycemia causes significant electrolyte shifts. 5

2. Determine Diabetes Type (Type 1 vs. Type 2)

• Islet autoantibodies: GAD65, IA-2, insulin autoantibodies, ZnT8—≥2 positive antibodies confirm autoimmune (type 1) diabetes and mandate immediate insulin therapy. 5
• Fasting C-peptide: Low or undetectable levels indicate insulin deficiency (type 1); normal or elevated levels suggest type 2. 5
• Clinical features favoring type 1: Rapid onset of polyuria/polydipsia, unintentional weight loss, ketosis at presentation, normal BMI, high physical activity, absence of metabolic syndrome features. 5
• Age is not exclusionary: Latent autoimmune diabetes in adults (LADA) can present in patients in their 60s. 5

3. Screen for Chronic Microvascular Complications

• Retinopathy: Dilated fundoscopic examination by ophthalmology within 1 month; HbA1c >6.5% sharply increases retinopathy prevalence. 5
• Nephropathy: Spot urine albumin-to-creatinine ratio and serum creatinine with estimated GFR to detect early kidney disease. 1, 5
• Neuropathy: 10-gram monofilament testing of feet; inquire about paresthesias, pain, or autonomic symptoms. 5

4. Cardiovascular Risk Assessment

• Fasting lipid panel: Total cholesterol, LDL-C, HDL-C, triglycerides to guide statin therapy. 1, 5
• Blood pressure measurement: Target <130/80 mm Hg for adults with diabetes. 1, 5
• Resting ECG: Screen for silent myocardial ischemia. 1, 5

5. Additional Laboratory Workup

• Hemoglobin electrophoresis or variant analysis: Identify structural hemoglobin abnormalities that explain HbA1c-glucose discordance. 3
• Complete blood count with iron studies: Evaluate for anemia (especially iron deficiency) that falsely elevates HbA1c. 3
• Thyroid-stimulating hormone (TSH): Screen for autoimmune thyroiditis if type 1 diabetes is confirmed. 5
• Tissue transglutaminase IgA with total IgA: Screen for celiac disease, which is associated with type 1 diabetes. 5
• Liver enzymes (ALT, AST): Identify non-alcoholic fatty liver disease, common in type 2 diabetes. 5

Common Pitfalls to Avoid

• Do not diagnose diabetes or initiate treatment based on a single discordant HbA1c without repeat confirmation; this violates ADA standards. 2
• Do not assume type 2 diabetes solely based on age; order autoantibody testing in atypical presentations (normal BMI, high activity, acute onset). 5
• Do not average discordant HbA1c results from different methods; this provides no clinically useful information and may lead to inappropriate treatment decisions. 3
• Do not dismiss the elevated HbA1c as laboratory error without investigating conditions affecting red blood cell lifespan or hemoglobin structure. 3
• Do not use point-of-care glucose meters for diagnostic confirmation; only certified laboratory plasma glucose measurements are acceptable. 2
• Do not postpone repeat testing for 3–6 months; the appropriate interval is days to weeks. 2

Treatment Considerations Pending Confirmation

No glucose-lowering therapy (including metformin) should be initiated until the diagnosis is confirmed by repeat testing. 2 If repeat testing confirms diabetes with HbA1c ≥9% (as the initial 12.1% suggests), dual oral therapy (metformin plus a second agent) or even insulin should be considered to achieve rapid glycemic control. 1