In a 17-year-old with hyperglycemia and anemia (hemoglobin 11.8 g/dL, hematocrit 35.2%), what laboratory test should be ordered next?

Laboratory Testing for a 17-Year-Old with Hyperglycemia and Anemia

Order a hemoglobin A1c (HbA1c) test immediately to confirm diabetes diagnosis, along with a fasting plasma glucose (FPG) if not already obtained, and a comprehensive metabolic panel including serum creatinine with estimated glomerular filtration rate (eGFR). 1

Primary Diagnostic Tests

Diabetes Confirmation

• HbA1c ≥6.5% (48 mmol/mol) confirms diabetes when performed in a laboratory using an NGSP-certified method standardized to the DCCT assay 1
• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) on two separate occasions confirms diabetes 1
• In the absence of unequivocal hyperglycemia, abnormal results from two different tests (glucose and HbA1c) obtained on the same day or on different days are required for diagnosis 1
• Point-of-care HbA1c assays should not be used for diagnostic purposes due to lack of mandated proficiency testing 1

Renal Function Assessment

• Serum creatinine with eGFR calculation is essential given the concurrent anemia and hyperglycemia 1
• Spot urine albumin-to-creatinine ratio (ACR) should be obtained to screen for early diabetic nephropathy 2, 3
  • ACR ≥30 mg/g (≥3.5 mg/mmol) indicates microalbuminuria in adolescents 2, 4
  • This is the preferred screening strategy over 24-hour urine collection 2

Critical Consideration: Anemia's Effect on HbA1c

The presence of anemia (hemoglobin 11.8 g/dL, hematocrit 35.2%) may falsely alter HbA1c results, making interpretation problematic. 1, 5

• Conditions with shortened red blood cell survival or decreased mean RBC age falsely lower HbA1c results compared to actual mean glycemia, regardless of assay method 1
• Iron-deficiency anemia is reported to increase HbA1c results 1
• In the presence of anemia affecting red blood cell turnover, only blood glucose criteria should be used to diagnose diabetes 1

Additional Anemia Workup Required

• Complete blood count with red cell indices (MCV, MCH, MCHC) to characterize the anemia type 5
• Serum ferritin to assess for iron deficiency 5
• Reticulocyte count to evaluate red blood cell turnover 1
• Consider vitamin B12 and folate levels if macrocytic anemia is present 1

Secondary Tests Based on Clinical Context

If Type 1 Diabetes is Suspected

• Diabetes autoantibodies (GAD65, IA-2, ZnT8, insulin autoantibodies) to confirm type 1 diabetes 6
• C-peptide level to assess beta-cell function and differentiate type 1 from type 2 diabetes 6
• Urine or blood ketones if blood glucose is consistently >300 mg/dL (16.7 mmol/L) or if symptoms of ketoacidosis are present 1

Comprehensive Metabolic Assessment

• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) as dyslipidemia commonly coexists with diabetes 1
• Serum electrolytes (sodium, potassium) 1
• Liver function tests if clinically indicated 1
• Thyroid-stimulating hormone (TSH) as autoimmune thyroid disease is common with type 1 diabetes 1

Common Pitfalls to Avoid

HbA1c Interpretation Errors

• Do not rely solely on HbA1c for diagnosis in the presence of anemia - confirm with fasting or random glucose measurements 1
• If hemoglobin variants are suspected (based on ethnicity or family history), use an HbA1c assay without interference from abnormal hemoglobins 1
• An updated list of HbA1c interferences is available at www.ngsp.org/interf.asp 1

Glucose Testing Considerations

• Laboratory measurement of plasma glucose using enzymatic assay techniques is required - do not use capillary glucose meters for diagnosis 1
• If initial FPG is ≥126 mg/dL with high suspicion for diabetes, perform an oral glucose tolerance test (OGTT) for confirmation 1
• A 2-hour postload value ≥200 mg/dL (11.1 mmol/L) during OGTT confirms diabetes and should be repeated on an alternate day 1

Microalbuminuria Screening Limitations

• Spot ACR has substantial day-to-day variability, particularly in the normoalbuminuric range 7
• For patients with normoalbuminuria (ACR <27 mg/g), a change >±467% is required to indicate significant change with 95% certainty 7
• Age affects spot ACR independently - false-positive rates increase with age 4

Algorithmic Approach

1. Immediate priority: HbA1c (laboratory-based, NGSP-certified) + FPG if not done 1
2. Concurrent with #1: Complete metabolic panel with creatinine/eGFR 1
3. Same visit: Spot urine ACR, CBC with indices, ferritin, reticulocyte count 1, 2, 5
4. If HbA1c unreliable due to anemia: Use glucose criteria exclusively for diagnosis 1
5. If diabetes confirmed: Add autoantibodies, C-peptide, lipid panel, TSH 1, 6
6. If glucose >300 mg/dL or symptomatic: Add ketone testing 1