What type of diabetes is indicated by a C-peptide (Connecting peptide) level of less than 0.5 ng/mL?

Type 1 Diabetes

Your patient has Type 1 diabetes based on the C-peptide of 0.5 ng/mL (approximately 0.17 nmol/L) combined with negative GAD antibodies (<0.5). 1, 2

Diagnostic Interpretation

C-peptide Analysis

• A C-peptide level of 0.5 ng/mL (approximately 0.17 nmol/L or 170 pmol/L) falls well below the 200 pmol/L threshold that the American Diabetes Association uses to diagnose Type 1 diabetes. 1, 2
• This level indicates severe insulin deficiency and absolute dependence on exogenous insulin for survival. 2
• Values <200 pmol/L (<0.6 ng/mL) are definitively consistent with Type 1 diabetes according to current ADA classification guidelines. 1, 2

Antibody-Negative Type 1 Diabetes

• Your patient represents the 5-10% of adults with Type 1 diabetes who are antibody-negative (GAD <0.5). 1
• The absence of GAD antibodies does NOT exclude Type 1 diabetes when C-peptide is this low. 1
• In antibody-negative cases, C-peptide becomes the primary diagnostic tool for distinguishing Type 1 from Type 2 diabetes. 2, 3

Clinical Algorithm for This Patient

Immediate Classification Steps

1. Confirm the diagnosis is Type 1 diabetes based on C-peptide <200 pmol/L 1, 2
2. Consider testing additional antibodies (IA-2, ZnT8) if not already done, though negative results won't change the diagnosis given this C-peptide level 1
3. Rule out monogenic diabetes only if clinical features suggest it (A1C <7.5% at diagnosis, parent with diabetes, renal cysts, or severe insulin resistance without obesity) 1

Treatment Implications

• This patient requires insulin therapy for survival - the C-peptide level indicates essentially no endogenous insulin production. 2, 4
• Oral agents or non-insulin therapies are inappropriate given the degree of insulin deficiency. 5, 6
• The patient should be educated about diabetic ketoacidosis risk and monitored accordingly. 2

Important Caveats

Testing Considerations

• Ensure C-peptide was not measured within 2 weeks of a hyperglycemic emergency, as this would invalidate results. 1, 2
• If concurrent glucose was <70 mg/dL at time of testing, consider repeating - though values this low (<200 pmol/L) are diagnostic regardless. 1
• Very low C-peptide levels like this (<80 pmol/L or 0.24 ng/mL) do not require repeat testing for confirmation. 1, 2

Differential Diagnosis Exclusions

• Type 2 diabetes is excluded - C-peptide would be >600 pmol/L (>1.8 ng/mL) in Type 2 diabetes. 1, 7, 3
• MODY is unlikely without family history or other clinical features, and MODY typically shows persistent C-peptide production. 1, 5
• The intermediate range (200-600 pmol/L) where MODY or insulin-treated Type 2 could be considered does not apply here. 1, 2

Age and Presentation

• Type 1 diabetes can occur at any age, including elderly patients, so age alone should not influence this diagnosis. 3
• The combination of low C-peptide with negative antibodies is well-recognized in adult-onset Type 1 diabetes. 1, 6