====== NPH Insulin ======

NPH (Neutral Protamine Hagedorn) insulin is an intermediate-acting insulin used for basal glucose control.

It has a pronounced peak and shorter duration compared to long-acting insulin analogs.

→ [[endocrine:insulin:start|Insulin Therapy]]

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===== Mechanism of Action =====

NPH insulin binds to the insulin receptor (tyrosine kinase receptor).

This activates:

  * IRS signaling pathways
  * PI3K/Akt cascade
  * GLUT4 translocation in muscle and adipose tissue

Primary effect:

  * Suppression of hepatic glucose production
  * Basal glucose control

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===== Protraction Mechanism =====

NPH insulin is human insulin complexed with:

  * Protamine

Protamine slows insulin absorption after subcutaneous injection.

After injection:

  * Protamine must be enzymatically degraded
  * Insulin is gradually released

This produces:

  * Delayed onset
  * Clear peak
  * Intermediate duration

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===== Pharmacokinetics =====

Onset:
  * 1–2 hours

Peak:
  * 4–8 hours (pronounced peak)

Duration:
  * 12–18 hours

Compared to:

  * [[endocrine:insulin:glargine|Glargine]] → shorter duration, clear peak
  * [[endocrine:insulin:detemir|Detemir]] → more variability
  * [[endocrine:insulin:degludec|Degludec]] → much shorter duration

Often requires twice-daily dosing.

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===== Clinical Use =====

  * Basal insulin (older regimens)
  * Sometimes combined in premixed formulations
  * Cost-effective option

Historically widely used before modern basal analogs.

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===== Disadvantages =====

  * Pronounced peak increases hypoglycemia risk
  * Higher nocturnal hypoglycemia risk
  * Greater day-to-day variability
  * Often requires twice-daily dosing

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===== Adverse Effects =====

  * Hypoglycemia (especially nocturnal)
  * Weight gain
  * Injection site reactions

Risk increased with:

  * Irregular meals
  * Missed food intake
  * Excess dosing

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===== NPH vs Long-Acting Basal Analogs =====

[[endocrine:insulin:glargine|Glargine]]:
  * No pronounced peak
  * Lower nocturnal hypoglycemia

[[endocrine:insulin:detemir|Detemir]]:
  * More stable pharmacokinetics

[[endocrine:insulin:degludec|Degludec]]:
  * Ultra-long duration
  * Most stable profile

NPH:
  * Has peak
  * Higher variability
  * Less expensive

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===== Clinical Pearls =====

  * Intermediate-acting insulin
  * Complexed with protamine
  * Clear peak at 4–8 hours
  * Higher hypoglycemia risk than analogs
  * Often requires twice-daily dosing
  * Lower cost option

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===== Related =====

  * [[endocrine:insulin:start|Insulin Therapy]]
  * [[endocrine:insulin:glargine|Glargine]]
  * [[endocrine:insulin:detemir|Detemir]]
  * [[endocrine:insulin:degludec|Degludec]]
  * [[endocrine:diabetes:start|Diabetes Pharmacology]]