A 22-year-old man is brought to the emergency department with altered consciousness. He is known to have type 1 diabetes. Blood glucose is 38 mg/dL. He is given IV dextrose and recovers. His C-peptide level (drawn at time of hypoglycemia) is undetectable. Which condition BEST explains undetectable C-peptide during hypoglycemia?

• A Insulinoma secreting excess endogenous insulin
• B Exogenous insulin administration (or failure of endogenous insulin secretion in T1DM) ✓
• C Sulfonylurea overdose stimulating beta-cell insulin release
• D Reactive hypoglycemia from rapid carbohydrate absorption

Explanation

C-peptide is co-secreted with endogenous insulin from beta-cells in equimolar amounts and has a longer half-life than insulin. In type 1 diabetes, beta-cells are destroyed, so both endogenous insulin and C-peptide are absent. Exogenous insulin administration also suppresses endogenous insulin (and hence C-peptide) due to hypoglycemia-induced feedback. An undetectable C-peptide in the context of hypoglycemia confirms exogenous insulin as the cause (either therapeutic in T1DM or factitious). Insulinoma secretes endogenous insulin, so both insulin and C-peptide are elevated simultaneously. Sulfonylureas stimulate beta-cells, resulting in high C-peptide alongside high insulin. Reactive hypoglycemia involves endogenous insulin hypersecretion, also producing elevated C-peptide.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.