What type of insulin is neither long-acting nor short-acting?

Intermediate-Acting Insulin

Intermediate-acting insulin is neither long-acting nor short-acting, with NPH (Neutral Protamine Hagedorn) and lente insulins being the primary examples in this category. 1

Classification of Insulin Types

The American Diabetes Association categorizes insulins into four distinct duration categories 1:

• Rapid-acting: Insulin lispro and insulin aspart 1
• Short-acting: Regular insulin 1
• Intermediate-acting: NPH and lente insulins 1
• Long-acting: Ultralente and insulin glargine 1

Intermediate-Acting Insulin Characteristics

NPH Insulin (Neutral Protamine Hagedorn)

• Onset and duration: NPH has an onset of action of 2-4 hours with a peak action period, rather than providing truly peakless basal coverage 2
• Mechanism: NPH is created by combining human insulin with protamine sulfate under conditions that promote crystal formation 3
• Pharmacodynamics: In healthy subjects receiving subcutaneous NPH (0.4 unit/kg), the median maximum effect occurred at 6.5 hours (range: 2.8 to 13 hours) 3
• Peak serum concentration: Occurs at approximately 4 hours (range: 1 to 12 hours) after subcutaneous injection 3

Lente Insulin

• Formulation: Lente insulins contain zinc ions (Zn2+) that contribute to their intermediate-acting properties 1
• Duration category: Classified as intermediate-acting alongside NPH 1

Critical Mixing Considerations

NPH Compatibility

• Protamine-based advantage: NPH can be mixed with rapid-acting or short-acting insulins without significant blunting of rapid-acting insulin onset 4
• Flexible timing: When NPH is mixed with rapid-acting insulin, the mixture can be used immediately or stored for future use without degradation 4
• Clinical application: The mixture should be injected within 15 minutes before a meal when combined with rapid-acting insulin 1

Lente Insulin Limitations

• Zinc-binding problem: Zinc ions in lente insulins bind with short-acting insulin and delay its onset of action unpredictably, with binding equilibrium potentially taking up to 24 hours 1, 4
• Phosphate incompatibility: Mixing phosphate-buffered insulins (such as NPH) with lente insulins causes zinc phosphate precipitation, converting longer-acting insulin to short-acting insulin unpredictably 1, 4
• Recommendation: Mixing short-acting and lente insulins is not recommended except for patients already adequately controlled on such a mixture 1

Premixed Formulations

• Commercial availability: Premixed insulins containing intermediate-acting insulin combined with short- or rapid-acting insulin are available (e.g., 70% NPH/30% regular, 50% NPH/50% regular, 75% NPL/25% insulin lispro) 1
• NovoLog Mix 70/30: Contains 30% short-acting and 70% long-acting insulin aspart with protamine, providing intermediate-acting coverage 5