What does a C‑peptide level of 0.98 ng/mL indicate about endogenous insulin secretion?

C-Peptide of 0.98 ng/mL: Interpretation and Clinical Significance

Primary Interpretation

A C-peptide level of 0.98 ng/mL (approximately 330 pmol/L) falls in the intermediate range and indicates partial preservation of endogenous insulin secretion, most consistent with type 2 diabetes, MODY (maturity-onset diabetes of the young), or early/slowly progressive type 1 diabetes. 1, 2

Diagnostic Framework

Classification by C-Peptide Thresholds

The American Diabetes Association provides clear cutoffs for interpretation: 1, 2

• <0.24 ng/mL (<80 pmol/L): Absolute insulin deficiency; definitive type 1 diabetes requiring insulin for survival 1, 2
• 0.24–0.6 ng/mL (80–200 pmol/L): Consistent with type 1 diabetes 1, 2
• 0.6–1.8 ng/mL (200–600 pmol/L): Intermediate zone where your patient falls—may indicate type 1 diabetes, MODY, or insulin-treated type 2 diabetes 1, 2
• >1.8 ng/mL (>600 pmol/L): Strongly suggests type 2 diabetes with preserved beta-cell function 1, 2

Your Patient's Value (0.98 ng/mL)

This level demonstrates meaningful residual insulin production but is insufficient to exclude progressive beta-cell failure. 2 The clinical context—age at diagnosis, body habitus, presence of ketoacidosis, symptom severity, and autoantibody status—becomes critical for accurate classification. 1, 2

Algorithmic Approach to Further Evaluation

Step 1: Check Islet Autoantibodies

Measure GAD65, IA-2, and ZnT8 antibodies immediately. 2

• If antibody-positive: Diagnosis is autoimmune diabetes (type 1 or LADA) regardless of C-peptide level, requiring lifelong insulin therapy 2
• If antibody-negative: Proceed to clinical phenotyping below 1

Step 2: Clinical Phenotype Assessment

Age, BMI, and presentation pattern guide interpretation: 3

• Younger age (<35 years), lower BMI, severe symptoms (DKA), rapid progression: More likely type 1 diabetes despite intermediate C-peptide 2, 3
• Older age (>35 years), higher BMI, gradual onset, obesity: More likely type 2 diabetes or MODY 1, 4

Step 3: Consider Genetic Testing

If antibody-negative with strong family history and intermediate C-peptide, test for monogenic diabetes (MODY). 1, 5 MODY patients often maintain C-peptide in this range for years and may respond to sulfonylureas rather than insulin. 1

Treatment Implications Based on C-Peptide Level

If Type 2 Diabetes is Confirmed

Initiate metformin as first-line therapy because preserved beta-cell function (C-peptide 0.98 ng/mL) makes the patient an excellent candidate for insulin-sensitizing agents. 4

• Implement intensive lifestyle modification with nutrition counseling targeting weight reduction 4
• Target at least 60 minutes daily of moderate-to-vigorous exercise 4
• Monitor HbA1c every 3 months and intensify treatment if target <7.0% is not achieved 4

If Type 1 Diabetes/LADA is Confirmed

Transition immediately to basal-bolus insulin regimen or insulin pump therapy with continuous glucose monitoring. 2

• Multiple daily injections with basal and mealtime insulin are required 2
• Consider automated insulin delivery systems for optimal control 2
• Monitor closely for diabetic ketoacidosis, especially during illness or when glucose >250 mg/dL 2

Prognostic Significance

A C-peptide of 0.98 ng/mL predicts ongoing beta-cell function but does not guarantee stability. 5, 3

• In type 1 diabetes, this level suggests slower progression but eventual complete insulin dependence is likely 2, 3
• Younger patients with lower BMI and lower initial C-peptide tend to show rapid decline 3
• In type 2 diabetes, this level indicates the patient may respond to oral agents and lifestyle modification before requiring insulin 4, 5

Critical Testing Considerations

Ensure proper testing conditions to avoid misinterpretation: 1, 2

• Do not test within 2 weeks of diabetic ketoacidosis or hyperglycemic emergency 1, 2
• A random C-peptide within 5 hours of eating is acceptable for classification; fasting is not required 1, 2
• If concurrent glucose was <70 mg/dL at time of sampling, repeat the test as hypoglycemia suppresses C-peptide 1
• For insulin-treated patients, C-peptide must be measured before considering insulin discontinuation 1

Common Pitfalls to Avoid

Do not assume intermediate C-peptide excludes type 1 diabetes. 2 Approximately 5–10% of adults with type 1 diabetes are antibody-negative, and 40% of adults with new type 1 diabetes are initially misdiagnosed as type 2 diabetes. 2

Do not use C-peptide alone to determine insulin therapy eligibility. 4 The American Diabetes Association recommends that low C-peptide should not be a prerequisite for insulin initiation or insulin-pump coverage in patients who are clinically insulin-deficient. 4

Recognize that C-peptide does not predict response to intensive insulin therapy once insulin deficiency is established. 1, 4 Treatment decisions should be based on clinical presentation and glycemic control, not C-peptide levels alone. 4