Can C-peptide (connecting peptide), islet antibody, and anti-GAD (glutamic acid decarboxylase) tests be sent during an acute diabetic ketoacidosis (DKA) event?

Can C-peptide, Islet Antibodies, and Anti-GAD Be Sent During Acute DKA?

Yes, C-peptide, islet antibodies (including anti-GAD), and insulin levels should be sent during the acute DKA event to support diabetes classification, but treatment initiation should never be delayed pending these results. 1

Rationale for Testing During DKA

The primary goal is to distinguish autoimmune type 1 diabetes from other forms of diabetes presenting with DKA (such as ketosis-prone type 2 diabetes), which has critical implications for long-term management and patient counseling. 1, 2

What to Send Immediately

• C-peptide level - Measure during the acute event to assess endogenous insulin production 1
• Islet autoantibodies - Including anti-GAD (GAD65), IA-2, IA-2b, and ZnT8 antibodies 1
• Insulin level - To support the diagnostic workup 1
• Standard DKA labs - Urine ketones, acid-base status, electrolytes, and glucose 1

Critical Timing Considerations

The American Diabetes Association recommends NOT testing C-peptide within 2 weeks of a hyperglycemic emergency for routine diabetes classification purposes. 3 However, this recommendation applies to elective classification testing, not acute diagnostic workup during the DKA event itself.

Why Test During the Acute Event

• The ASCO guidelines explicitly state that "antibodies, insulin, and C-peptide levels should also be sent to support diagnosis" during acute presentation, even though "initiation of therapy should not be delayed pending results." 1
• Obtaining these tests during the acute event captures the patient's baseline state before insulin therapy is initiated, which is essential since insulin treatment will alter subsequent C-peptide measurements 3
• Approximately 25-40% of adults presenting with DKA may have ketosis-prone type 2 diabetes rather than type 1 diabetes, making this distinction clinically important 2, 4

Interpreting Results from DKA Presentation

C-peptide Interpretation

• <200 pmol/L (<0.6 ng/mL) - Consistent with type 1 diabetes 3, 5
• 200-600 pmol/L (0.6-1.8 ng/mL) - May indicate type 1 diabetes, MODY, or insulin-treated type 2 diabetes 3, 5
• >600 pmol/L (>1.8 ng/mL) - Suggests type 2 diabetes or ketosis-prone type 2 diabetes 5, 4

Autoantibody Interpretation

• Positive anti-GAD, IA-2, or ZnT8 - Confirms autoimmune type 1 diabetes regardless of C-peptide level 1, 5
• Negative antibodies - Does not exclude type 1 diabetes; approximately 5-10% of type 1 diabetes cases are antibody-negative, and up to 61% in some populations 5, 6

Important Clinical Caveats

Ethnic Variations

• Black South African patients with DKA had detectable C-peptide levels (>0.3 nmol/L) in 28% of cases, with most being anti-GAD-negative, suggesting ketosis-prone type 2 diabetes 4
• Vietnamese patients presenting with DKA showed 61% were negative for both anti-GAD and islet cell antibodies 6

Treatment Implications

• Never delay insulin therapy while waiting for antibody or C-peptide results - treat the DKA according to standard protocols immediately 1
• These tests inform long-term management decisions, not acute treatment 1, 2
• Patients with ketosis-prone type 2 diabetes may eventually discontinue insulin after DKA resolution, while true type 1 diabetes requires lifelong insulin 2

Common Pitfalls to Avoid

• Do not assume all DKA is type 1 diabetes - consider ketosis-prone type 2 diabetes, especially in patients with strong family history of type 2 diabetes, obesity (BMI >25 kg/m²), or cutaneous markers of insulin resistance 5, 2
• Do not repeat C-peptide testing if initial levels are very low (<80 pmol/L or <0.24 ng/mL) - this definitively indicates severe insulin deficiency 3, 5
• If concurrent glucose is <70 mg/dL when C-peptide is measured, consider repeating the test as hypoglycemia can suppress C-peptide 3