A 32-year-old woman presents with polyuria, polydipsia, and weight loss over 2 weeks. Fasting blood glucose is 280 mg/dL and random blood glucose is 320 mg/dL. She has no family history of diabetes. Which investigation is most appropriate to differentiate between Type 1 and Type 2 diabetes mellitus?

Explanation

## Differentiating Type 1 from Type 2 Diabetes **Key Point:** Serum C-peptide level is the gold standard investigation to distinguish Type 1 from Type 2 diabetes by assessing residual pancreatic beta-cell function. ### Why C-Peptide is Superior C-peptide is a marker of endogenous insulin secretion. It is cleaved from proinsulin in equimolar amounts with insulin but is not extracted by the liver, making it a reliable indicator of beta-cell function. | Feature | Type 1 Diabetes | Type 2 Diabetes | |---------|-----------------|------------------| | **C-Peptide Level** | Low or undetectable (<0.2 ng/mL) | Normal or elevated (>0.2 ng/mL) | | **Pathophysiology** | Autoimmune destruction of beta cells | Insulin resistance + beta-cell dysfunction | | **Onset** | Acute (days to weeks) | Gradual (months to years) | | **Autoantibodies** | Present (GAD, IA-2, ZnT8) | Absent | **High-Yield:** In this case, acute presentation with severe hyperglycemia and weight loss suggests Type 1 diabetes. A low C-peptide level would confirm autoimmune beta-cell destruction. **Clinical Pearl:** C-peptide is superior to fasting insulin because it is not affected by exogenous insulin therapy and reflects true endogenous secretion. ### Why Other Tests Are Insufficient - **HbA1c:** Reflects glycemic control over 3 months; does not differentiate between types - **OGTT:** Assesses glucose tolerance but does not indicate beta-cell function - **Fasting insulin:** Can be falsely elevated in Type 2 (hyperinsulinemia) and may be suppressed in Type 1; less specific than C-peptide