In a 23‑year‑old with severe type 2 diabetes (A1c 13 %) and a C‑peptide of 2.9 ng/mL measured without a simultaneous glucose, what does this result indicate about endogenous insulin secretion and how should it affect the current insulin regimen?

C-Peptide of 2.9 ng/mL in a 23-Year-Old with Severe Type 2 Diabetes

A C-peptide of 2.9 ng/mL (approximately 870 pmol/L) indicates robust endogenous insulin secretion and confirms type 2 diabetes with significant insulin resistance rather than type 1 diabetes, meaning this patient should be managed with insulin-sensitizing agents and lifestyle modification rather than assuming absolute insulin dependence. 1, 2

Interpretation of the C-Peptide Result

This C-peptide level is well above the threshold for type 2 diabetes:

• C-peptide >600 pmol/L (>1.8 ng/mL) strongly indicates type 2 diabetes with preserved beta-cell function 1, 2, 3
• At 2.9 ng/mL, this patient has approximately 5 times the upper limit that would suggest type 1 diabetes 1
• The elevated C-peptide confirms insulin resistance as the primary pathophysiologic defect, not absolute insulin deficiency 2

Key diagnostic thresholds for context:

• <0.6 ng/mL (<200 pmol/L): consistent with type 1 diabetes 1, 3
• 0.6-1.8 ng/mL (200-600 pmol/L): indeterminate zone (may indicate type 1, LADA, MODY, or long-standing type 2) 1, 3

• 1.8 ng/mL (>600 pmol/L): strongly suggests type 2 diabetes 1, 2, 3

Clinical Significance Despite Poor Glycemic Control

The paradox of high C-peptide with A1c of 13% reveals critical pathophysiology:

• In type 2 diabetes, insulin levels appear "normal or elevated" in absolute terms, but are disproportionately insufficient for the degree of hyperglycemia and insulin resistance present 4
• The beta cells are producing substantial insulin (evidenced by high C-peptide), but cellular insulin resistance prevents adequate glucose uptake 2
• This represents "relative insulin deficiency"—the pancreas cannot compensate adequately for severe insulin resistance despite robust secretory capacity 4, 5

Impact on Treatment Strategy

This C-peptide result fundamentally changes the therapeutic approach:

First-Line Management

• Initiate metformin immediately as first-line pharmacotherapy, as the preserved beta-cell function makes this patient an ideal candidate for insulin-sensitizing therapy 2
• Implement intensive lifestyle modification including nutrition counseling targeting weight reduction, as obesity drives insulin resistance in this population 4, 2
• Prescribe at least 60 minutes daily of moderate-to-vigorous exercise to enhance insulin sensitivity 2

Medication Intensification Algorithm

• Consider thiazolidinediones (pioglitazone) as they directly address insulin resistance by enhancing cellular responsiveness to the patient's endogenous insulin 2
• GLP-1 receptor agonists offer dual benefits: improving insulin secretion relative to glucose levels and promoting weight loss 6
• SGLT2 inhibitors provide insulin-independent glucose lowering and cardiovascular/renal protection 6

Role of Insulin Therapy

• Insulin may be needed temporarily given the severe hyperglycemia (A1c 13%), but this is for glycemic rescue, not because of absolute insulin deficiency 7, 5
• The goal should be insulin reduction or discontinuation as insulin-sensitizing agents take effect and weight loss occurs 5
• Approximately 94% of insulin-treated type 2 diabetes patients retain sufficient or borderline beta-cell reserves, making many candidates for insulin de-escalation 5

Critical Caveats About the Missing Glucose Value

The absence of simultaneous glucose creates an interpretive limitation:

• If the concurrent glucose was <70 mg/dL (<4 mmol/L), the C-peptide result should be repeated, as hypoglycemia can suppress C-peptide secretion 1, 3
• However, given the A1c of 13%, hypoglycemia at the time of testing is extremely unlikely 4
• A random C-peptide within 5 hours of eating is acceptable for diabetes classification and does not require fasting or stimulation testing 4, 1, 3
• For insurance documentation purposes (e.g., insulin pump coverage), fasting C-peptide should be measured when fasting glucose is ≤220 mg/dL, but this is not relevant for this patient's type 2 diabetes 4, 3

Monitoring Strategy

Given the severe hyperglycemia, aggressive monitoring is essential:

• Check A1c every 3 months and intensify treatment if target <7.0% is not achieved 2
• Finger-stick glucose monitoring is indicated when initiating or changing treatment regimens 2
• Reassess C-peptide is not necessary unless the clinical picture changes dramatically or autoimmune diabetes becomes suspected 7, 6

Why This Patient Does NOT Have Type 1 Diabetes

Multiple factors exclude type 1 diabetes:

• C-peptide of 2.9 ng/mL is incompatible with type 1 diabetes, where levels are typically <0.6 ng/mL 1
• Type 1 diabetes is characterized by "little or no insulin secretion, as manifested by low or undetectable levels of plasma C-peptide" 4
• The age of 23 years with obesity and severe hyperglycemia fits the type 2 diabetes phenotype, which increasingly affects younger adults 4
• If there were any clinical suspicion for latent autoimmune diabetes in adults (LADA), autoantibody testing (GAD65, IA-2, ZnT8) would be indicated, but the high C-peptide makes this diagnosis extremely unlikely 1

Common Pitfall to Avoid

Do not assume this young patient with severe diabetes needs lifelong insulin simply because of age or A1c level:

• Misdiagnosis occurs in 40% of adults with new diabetes, often due to age-based assumptions 1
• The robust C-peptide proves this patient has substantial insulin secretory capacity that can be leveraged with appropriate insulin-sensitizing therapy 2, 5
• The primary defect is insulin resistance, not insulin deficiency, and treatment should target the underlying pathophysiology 2