What are the appropriate investigations and management for a 17‑year‑old without a diabetes diagnosis who has an HbA1c of 42 mmol/mol (≈6 %) and laboratory findings consistent with iron‑deficiency anemia (low serum iron, low‑normal ferritin, elevated transferrin, low transferrin saturation, microcytic hypochromic red cells)?

Management of a 17-Year-Old with Prediabetes and Iron Deficiency

This 17-year-old requires immediate oral iron supplementation for confirmed iron deficiency while simultaneously undergoing investigation for the source of iron loss and lifestyle intervention for prediabetes.

Iron Deficiency Diagnosis and Immediate Management

Diagnostic Confirmation

• The laboratory profile confirms iron deficiency: serum iron 5 µmol/L (low), ferritin 16 µg/L (low-normal), transferrin 3.6 g/L (elevated), and transferrin saturation 0.06 (markedly low). 1
• The microcytic hypochromic indices (MCV 77 fL, MCH 24 pg) combined with these iron studies establish iron-deficient erythropoiesis. 2, 1
• The low-normal ferritin (16 µg/L) with severely reduced transferrin saturation (<16%) indicates true iron deficiency despite the borderline ferritin, because ferritin <30 µg/L confirms depleted iron stores. 2
• The hemoglobin of 129 g/L is still within normal range, indicating this is early-stage iron deficiency before frank anemia has developed—making intervention now critical to prevent progression. 3

Immediate Treatment Protocol

• Start oral ferrous sulfate 200 mg three times daily (or 100 mg twice daily as an alternative regimen) immediately. 1, 4
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate causes intolerable gastrointestinal side effects. 1
• Adding ascorbic acid (vitamin C) enhances iron absorption. 1
• Continue iron supplementation for at least 3 months after hemoglobin normalizes to replenish iron stores. 1, 5

Expected Response and Monitoring

• Hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the primary cause. 2, 1
• Recheck complete blood count, ferritin, and transferrin saturation at 2 weeks to confirm response. 3
• Target ferritin >30 µg/L and transferrin saturation >20% to confirm adequate iron repletion. 3
• Monitor at 3-month intervals for the first year, then annually. 1

Investigation of Underlying Cause

Mandatory Workup in Adolescents

Even though this patient is young, iron deficiency at any age requires investigation for the source of iron loss—it should never be attributed solely to dietary insufficiency or growth demands without excluding pathology. 2, 1

Essential Investigations

1. Screen for celiac disease with tissue transglutaminase (tTG) antibody testing immediately. Celiac disease accounts for 3–5% of iron deficiency cases and is a critical diagnosis in adolescents. 2, 1

2. Detailed menstrual history (if female): Heavy menstrual bleeding is the most common cause of iron deficiency in adolescent females. 1, 6

3. Assess for gastrointestinal blood loss:

   • Urinalysis or urine microscopy to exclude hematuria. 2
   • Stool for occult blood if any GI symptoms present. 2
   • Consider Helicobacter pylori testing, as chronic infection can impair iron absorption. 6

4. Dietary assessment: Evaluate for inadequate iron intake, though this alone rarely causes iron deficiency in developed countries without an underlying absorption problem. 6

5. Rule out malabsorption disorders: Beyond celiac disease, consider inflammatory bowel disease if any GI symptoms (diarrhea, abdominal pain) are present. 2

When to Consider Genetic Disorders

Genetic causes of iron deficiency are extremely rare but should be considered if:

• Failure to respond to oral iron therapy within 2–4 weeks. 1, 7
• Family history of refractory anemia. 1
• Remarkably low transferrin saturation with low-normal ferritin (which this patient has). 7

Iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 mutations presents with very low transferrin saturation, low-normal ferritin, and failure to respond to oral iron but partial response to IV iron. 7 However, this diagnosis should only be pursued after excluding common causes and documenting treatment failure. 1

Prediabetes Management

Diagnostic Interpretation

• HbA1c of 42 mmol/mol (6.0%) indicates impaired glucose tolerance (prediabetes). [@laboratory comment@]
• This places the patient at increased risk for progression to type 2 diabetes and cardiovascular disease. [@laboratory comment@]

Immediate Interventions

1. Lifestyle modification is the cornerstone of prediabetes management:

   • Structured weight loss program if overweight (target 5–7% body weight reduction).
   • Minimum 150 minutes per week of moderate-intensity aerobic exercise.
   • Dietary counseling emphasizing reduced refined carbohydrates and increased fiber intake.

2. Annual follow-up with repeat HbA1c to monitor for progression to diabetes. [@laboratory comment@]

3. Cardiovascular risk assessment including lipid profile and blood pressure monitoring. [@laboratory comment@]

Critical Interaction Between Iron Deficiency and HbA1c

Important caveat: Iron deficiency can falsely elevate HbA1c because reduced red cell turnover prolongs hemoglobin glycation time. After iron repletion, repeat HbA1c in 3 months to obtain an accurate baseline glucose control measurement. [@general medicine knowledge@]

Common Pitfalls to Avoid

1. Do not assume iron deficiency in adolescents is benign or solely dietary. Investigation for pathologic causes is mandatory at any age. 2, 1

2. Do not rely on ferritin alone when it is borderline (15–30 µg/L). The severely reduced transferrin saturation of 6% confirms true iron deficiency despite the low-normal ferritin. 2, 1

3. Do not overlook celiac disease screening. This is present in 3–5% of iron deficiency cases and is easily missed without serologic testing. 2

4. Do not accept a single cause without complete evaluation. Combined deficiencies can coexist (e.g., iron deficiency with B12 or folate deficiency), though this patient's normal hemoglobin and MCV pattern make combined deficiency less likely. 2, 1

5. Do not stop iron supplementation when hemoglobin normalizes. Continue for 3 months after correction to replenish iron stores. 1, 5

6. Do not interpret the current HbA1c as definitive until after iron repletion. Recheck in 3 months for accurate glucose assessment. [@general medicine knowledge@]