====== Insulin Therapy ======

Insulin is the most effective glucose-lowering therapy available.

It replaces or supplements endogenous insulin when pancreatic beta-cell function is inadequate or absent.

Used in:

  * Type 1 Diabetes (required)
  * Advanced Type 2 Diabetes
  * DKA / HHS
  * Severe hyperglycemia
  * Hospital settings

→ [[endocrine:diabetes:start|Diabetes Pharmacology]]

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

Insulin binds to the insulin receptor (a tyrosine kinase receptor).

This activates:

  * IRS signaling pathways
  * PI3K/Akt cascade
  * GLUT4 translocation (muscle & adipose)

Effects:

Liver:
  * ↓ Gluconeogenesis
  * ↑ Glycogen synthesis
  * ↑ Lipogenesis

Muscle:
  * ↑ Glucose uptake
  * ↑ Glycogen storage

Adipose:
  * ↑ Glucose uptake
  * ↓ Lipolysis

Insulin is anabolic.

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===== Insulin Comparison Table =====

^ Type ^ Agent ^ Onset ^ Peak ^ Duration ^ Dosing Role ^ Key Features ^
| Rapid-Acting | [[endocrine:insulin:lispro|Lispro]] | 10–15 min | ~1 hr | 3–5 hr | Mealtime | Rapid absorption, less stacking |
| Rapid-Acting | [[endocrine:insulin:aspart|Aspart]] | 10–20 min | 1–3 hr | 3–5 hr | Mealtime | Structurally modified, rapid profile |
| Rapid-Acting | [[endocrine:insulin:glulisine|Glulisine]] | 10–20 min | ~1 hr | 3–5 hr | Mealtime | Rapid analog, comparable to lispro/aspart |
| Short-Acting | [[endocrine:insulin:regular|Regular]] | 30–60 min | 2–4 hr | 6–8 hr | Mealtime / IV use | Only insulin used IV (DKA, HHS) |
| Intermediate | [[endocrine:insulin:nph|NPH]] | 1–2 hr | 4–8 hr | 12–18 hr | Basal (older regimens) | Protamine-bound, clear peak |
| Long-Acting | [[endocrine:insulin:glargine|Glargine]] | 1–2 hr | Minimal | ~24 hr | Basal | pH-dependent precipitation |
| Long-Acting | [[endocrine:insulin:detemir|Detemir]] | 1–2 hr | Minimal | 12–24 hr | Basal | Albumin binding, may require BID |
| Ultra-Long | [[endocrine:insulin:degludec|Degludec]] | ~1 hr | None | >42 hr | Basal | Multi-hexamer depot, very stable |

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===== Types of Insulin =====

Insulins are categorized by onset and duration.


==== Rapid-Acting (Mealtime) ====

  * [[endocrine:insulin:lispro|Lispro]]
  * [[endocrine:insulin:aspart|Aspart]]
  * [[endocrine:insulin:glulisine|Glulisine]]

Onset: 10–30 minutes  
Duration: 3–5 hours  

Used for:

  * Mealtime glucose control
  * Correction dosing

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==== Short-Acting ====

  * [[endocrine:insulin:regular|Regular Insulin]]

Onset: 30–60 minutes  
Duration: 6–8 hours  

Used in:

  * IV infusion (DKA)
  * Some prandial regimens

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==== Intermediate-Acting ====

  * [[endocrine:insulin:nph|NPH]]

Duration: ~12–18 hours  

Older basal insulin option.

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==== Long-Acting (Basal) ====

  * [[endocrine:insulin:glargine|Glargine]]
  * [[endocrine:insulin:detemir|Detemir]]

Provide steady background insulin.

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==== Ultra-Long Acting ====

  * [[endocrine:insulin:degludec|Degludec]]

Very flat, prolonged profile (>24 hours).

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===== Basal-Bolus Concept =====

Physiologic insulin secretion includes:

  * Basal insulin (background suppression of hepatic glucose production)
  * Bolus insulin (mealtime glucose control)

Modern therapy mimics this:

Basal insulin:
  * Once daily (glargine, degludec)

Bolus insulin:
  * Rapid-acting insulin before meals

This is the most physiologic regimen.

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===== Initiating Insulin (Type 2) =====

Step 1:
  * Start basal insulin
  * Titrate based on fasting glucose

Step 2:
  * Add prandial insulin if needed

Continue:

  * [[endocrine:biguanides:metformin|Metformin]] when possible
  * Consider combination with:
      * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
      * [[endocrine:sglt2:start|SGLT2 Inhibitors]]

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

Common:

  * Hypoglycemia
  * Weight gain

Serious:

  * Severe hypoglycemia
  * Hypokalemia (high-dose therapy)

Hypoglycemia symptoms:

  * Sweating
  * Tremor
  * Confusion
  * Seizures (severe)

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===== DKA & HHS =====

Insulin deficiency leads to:

  * Unchecked lipolysis
  * Ketone production
  * Metabolic acidosis (DKA)

Treatment requires:

  * IV [[endocrine:insulin:regular|Regular Insulin]]
  * Fluid resuscitation
  * Electrolyte management

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===== Insulin vs Other Therapies =====

Compared to:

  * [[endocrine:sulfonylureas:start|Sulfonylureas]] → direct replacement vs stimulation
  * [[endocrine:biguanides:metformin|Metformin]] → more potent glucose lowering
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]] → more hypoglycemia, more weight gain
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]] → no intrinsic CV benefit

Insulin is unmatched in glucose-lowering potency.

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

  * Most potent antihyperglycemic therapy
  * Required in Type 1 Diabetes
  * Basal suppresses hepatic glucose output
  * Bolus controls meals
  * Causes weight gain
  * Hypoglycemia is primary risk
  * Continue metformin when possible

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===== Related =====

  * [[endocrine:diabetes:start|Diabetes Pharmacology]]
  * [[endocrine:biguanides:metformin|Metformin]]
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[endocrine:sulfonylureas:start|Sulfonylureas]]