A 52-year-old obese man with a 10-year history of diabetes presents with fasting blood glucose 180 mg/dL despite metformin and glibenclamide therapy. Which finding would most reliably indicate that his diabetes is Type 2 rather than Type 1 with late presentation?

Explanation

## C-Peptide: The Gold-Standard Marker of Beta-Cell Function **Key Point:** Serum C-peptide reflects endogenous insulin secretion independent of exogenous insulin. Detectable C-peptide with elevated insulin indicates preserved beta-cell function, diagnostic of Type 2 DM. In Type 1 DM, C-peptide is low or absent. ### Pathophysiology of C-Peptide Secretion 1. **Beta-cell synthesizes proinsulin** → cleaved into insulin + C-peptide (equimolar amounts) 2. **Type 2 DM:** Beta cells still functional → both insulin AND C-peptide elevated 3. **Type 1 DM:** Beta cells destroyed → both insulin AND C-peptide low/absent 4. **Exogenous insulin therapy:** Suppresses endogenous secretion → C-peptide drops (but exogenous insulin remains high) **High-Yield:** C-peptide is NOT suppressed by exogenous insulin therapy, making it the most reliable marker of residual beta-cell function. A patient on insulin with detectable C-peptide still has endogenous insulin production. ### Comparative Diagnostic Value | Marker | Type 1 DM | Type 2 DM | Late-Onset Type 1 (LADA) | |--------|-----------|-----------|------------------------| | **Fasting C-peptide** | <0.3 ng/mL | >0.8 ng/mL | Low-normal to low | | **Fasting insulin** | Low | Elevated | Low-normal | | **Autoimmune antibodies** | Present | Absent | Present | | **Response to oral agents** | Poor | Good initially | Variable | | **Ketosis risk** | High | Low | Moderate | **Clinical Pearl:** In this case, the patient has been on oral agents (metformin + glibenclamide) for 10 years without developing DKA. This suggests preserved beta-cell function. A detectable C-peptide >0.8 ng/mL with elevated insulin confirms Type 2 DM with secondary beta-cell exhaustion, not Type 1 DM with late presentation. **Warning:** Do NOT rely on age or symptom onset alone — Type 1 DM can present in adults (LADA, Latent Autoimmune Diabetes in Adults). Only C-peptide and autoimmune markers reliably distinguish them. ### Clinical Application C-peptide testing is indicated when: - Distinguishing Type 1 from Type 2 DM in ambiguous cases - Assessing residual beta-cell function in long-standing diabetes - Evaluating response to beta-cell-preserving therapies (GLP-1 agonists, DPP-4 inhibitors) - Determining prognosis and insulin requirement trajectory [cite:KD Tripathi 8e Ch 34; Harrison 21e Ch 417]