A 45-year-old woman with type 1 diabetes uses insulin aspart at mealtimes. The rapid onset of insulin aspart compared to regular insulin is attributed to which structural modification?

• A Attachment of a fatty acid side chain enabling albumin binding in subcutaneous tissue
• B Addition of zinc ions to stabilize monomeric form at the injection site
• C Reversal of the B-chain sequence from B1 to B30, increasing receptor affinity
• D Substitution of proline at B28 with aspartic acid, reducing self-association into hexamers ✓

Explanation

Insulin aspart has proline at position B28 replaced by aspartic acid, which introduces a charge repulsion that reduces hexamer formation, allowing faster absorption of monomers. Zinc addition (B) would slow absorption. Reversed B-chain (C) does not describe aspart. Fatty acid side chain (A) describes insulin detemir or degludec.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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