What are the investigations for the evaluation of diabetes?

Laboratory Investigations for Diabetes Evaluation

Initial Diagnostic Testing

For diagnosing diabetes, measure either fasting plasma glucose (FPG ≥126 mg/dL), 2-hour plasma glucose during 75-g oral glucose tolerance test (≥200 mg/dL), HbA1c (≥6.5%), or random plasma glucose (≥200 mg/dL with classic symptoms), with confirmation by repeat testing unless hyperglycemic crisis is present. 1

Primary Diagnostic Tests

• Fasting Plasma Glucose (FPG): Requires 8-hour fast; diagnostic threshold ≥126 mg/dL (7.0 mmol/L) 1, 2
• 2-Hour Oral Glucose Tolerance Test (OGTT): Using 75-g glucose load; diagnostic threshold ≥200 mg/dL (11.1 mmol/L) 1, 2
• HbA1c: Must use NGSP-certified laboratory method; diagnostic threshold ≥6.5% (48 mmol/mol) 1, 3
• Random Plasma Glucose: ≥200 mg/dL (11.1 mmol/L) with classic symptoms (polyuria, polydipsia, weight loss) 1, 2

Confirmation Requirements

• Repeat the same test or use a different test on a separate occasion unless patient presents with hyperglycemic crisis 1
• Two different abnormal tests (e.g., HbA1c and FPG) performed simultaneously also confirm diagnosis 1, 2

Comprehensive Initial Laboratory Evaluation

Once diabetes is diagnosed, obtain these baseline tests within the first year 1:

Metabolic Panel

• Fasting lipid profile: Total cholesterol, LDL, HDL, triglycerides 1
• Liver function tests 1
• Serum creatinine with calculated eGFR 1
• Thyroid-stimulating hormone (TSH): Particularly in type 1 diabetes, dyslipidemia, or women over 50 years 1

Kidney Function Assessment

• Spot urine albumin-to-creatinine ratio (uACR): Use first morning void sample 1, 4
• Begin annual screening 5 years after type 1 diabetes diagnosis in pubertal/post-pubertal individuals 3
• Screen at diagnosis for type 2 diabetes 1

Diabetes Classification Tests (When Needed)

For ambiguous presentations or phenotypic overlap between type 1 and type 2 diabetes, measure pancreatic autoantibodies and C-peptide to determine diabetes type. 2, 3

• Autoantibody panel: GAD65, insulin autoantibodies (IAA), IA-2/IA-2β, ZnT8, islet cell autoantibodies 2, 3
• C-peptide: Low or undetectable in type 1 diabetes; helps distinguish from type 2 in ambiguous cases 2, 3

Ongoing Monitoring Tests

Glycemic Control

• HbA1c: Every 3 months until target reached, then at least every 6 months 3, 4
• Target <7% for most non-pregnant adults 3
• Must use NGSP-certified laboratory methods 3, 4

Kidney Monitoring

• Annual uACR: Using morning spot urine samples 4
• Increase to every 6 months if eGFR <60 mL/min/1.73 m² or albuminuria >30 mg/g creatinine 3, 4

Additional Monitoring

• Serum potassium: In patients on ACE inhibitors, ARBs, or diuretics 1
• Vitamin B12: If on metformin 1

Critical Caveats and Special Situations

When NOT to Use HbA1c for Diagnosis

Use only plasma glucose criteria in conditions with altered red blood cell turnover: sickle cell disease, pregnancy (second/third trimesters), hemodialysis, recent blood loss/transfusion, or erythropoietin therapy. 1, 2, 3

Sample Handling

• Place glucose samples immediately in ice-water slurry and centrifuge within 15-30 minutes to prevent falsely low results from glycolysis 4
• Use tubes containing granulated citrate buffer for FPG samples 4

Assay Interference

• Marked discordance between HbA1c and plasma glucose suggests hemoglobin variant interference; use assay without interference or glucose-based criteria instead 1, 2

Point-of-Care Testing

• Point-of-care HbA1c for diagnosis should only use FDA-approved devices at CLIA-certified laboratories 3
• HbA1c does not measure glycemic variability or hypoglycemia 3

Pediatric Considerations

• In overweight/obese adolescents with diabetes, measure islet autoantibodies and C-peptide to distinguish type 1 from type 2 2
• Consider stress hyperglycemia in acutely ill children before diagnosing diabetes 2

Monogenic Diabetes

• Consider in antibody-negative patients, as monogenic diabetes is frequently misdiagnosed as type 1 diabetes 2