A type 1 diabetic on insulin glargine experiences persistent hypoglycemia at 3 AM despite appropriate bedtime dose. A contributing factor unique to insulin glargine's pharmacokinetics is:
- A Glargine is cleaved in subcutaneous tissue to active metabolites M1 and M2 with variable release kinetics ✓
- B Glargine forms microprecipitates at subcutaneous pH 7.4, delaying but occasionally causing unpredictable absorption peaks
- C Glargine binds IGF-1 receptors causing overnight GH suppression and insulin sensitization
- D Glargine inhibits hepatic glucose production more potently than NPH at the same plasma concentration
Correct answer: A. Glargine is cleaved in subcutaneous tissue to active metabolites M1 and M2 with variable release kinetics
Explanation
Insulin glargine (pI 6.7) precipitates at the neutral subcutaneous pH forming a depot; however, it is enzymatically cleaved in subcutaneous tissue to two active metabolites, M1 (des-ThrB30-GluA21 insulin) and M2. While the pharmacokinetic profile is generally flat over 24 hours, individual variability in subcutaneous tissue enzyme activity and adipose depot characteristics can occasionally create mild absorption variation contributing to nocturnal hypoglycemia, especially with incorrect injection site rotation or use of lipohypertrophic sites.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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