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Insulin

Last updated: February 8, 2021

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Insulin is an anabolic peptide hormone that is produced and secreted from β cells located in the islets of Langerhans of the pancreas. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Further important metabolic functions of insulin include the promotion of carbohydrate, amino acid, and fat storage in the liver, skeletal muscle, and adipose tissues. There are several insulin analogs (e.g., insulin glargine) with a different molecular structure but similar properties to human insulin, with differences mainly in the onset, peak, and duration of action. Insulin therapy is an important part of treatment for individuals with no or insufficient insulin production (e.g., diabetes mellitus, gestational diabetes). It is crucial that patients receiving insulin therapy undergo in-depth training to prevent potentially life-threatening conditions such as hypoglycemia as a result of an insulin overdose or drug interactions.

See also “Insulin therapy” and “Inpatient management of hyperglycemia.”

For synthesis and regulation of insulin see “Endocrine pancreas.”

Overview of the different types of insulin
Types of insulin Pharmacokinetics [1] Application [2][3] Additional considerations [1]
Rapid-acting insulin
Insulin lispro
  • Onset: 5–15 minutes
  • Peak: ∼ 1 hour
  • Duration: 3–4 hours
  • Insulin analogs
  • Rapid absorption due to immediate dissociation into individual insulin molecules
  • No time interval between injection and meal necessary
  • Usually combined with long-acting insulin
Insulin aspart
Insulin glulisine
Short-acting insulin
Regular insulin
  • Onset: ∼ 30 minutes
  • Peak: 2–3 hours
  • Duration: 4–6 hours
  • Recommended interval between injections and meals: 15–30 minutes
  • Often used in combination with long-acting insulin
  • The only insulin available for intravenous use
Intermediate-acting insulin
NPH insulin
  • Onset: 1–2 hours
  • Peak: 6–10 hours
  • Duration: 10–16 hours
  • Crystalline suspension consisting of regular insulin (with a high level of solubility) and protamine (with a low level of solubility)
  • Recommended interval between injections and meal, if it is the only antidiabetic drug used: 30–60 minutes
  • Often used in combination with rapid-acting or short-acting insulin
  • Usually administered twice daily
Long-acting insulin
Insulin glargine
  • Onset: 1–4 hours
  • Peak: flat; not defined
  • Duration: ∼ 24 hours
  • Insulin analogs
  • More consistent effect and longer duration of action compared to NPH insulin
  • Often used in combination with rapid or short-acting insulin
  • Administered once or twice daily
Insulin detemir
Insulin degludec
Mixed insulin
Mixed insulin
  • Typically a mixture of NPH insulin and either rapid-acting insulin or regular insulin, in a predefined ratio
  • Administered 2–3 times daily
  • Only requires one injection per application without the need to mix fast- and intermediate-acting insulin

Rapid-acting insulins are your favorite GAL pals (Glulisine, Aspart, Lispro).

Insulin function and metabolic effects

Metabolic actions of insulin
Increases Decreases
Carbohydrate metabolism
Lipid metabolism
Protein metabolism
  • Proteolysis
  • Other physiologic actions of insulin
    • Cellular uptake of potassium [10]
    • Sodium retention by the kidney [11]
    • Ovarian androgen hypersecretion [12]
    • Decreased fibrinolytic activity [13]
    • Secretion of gastric acid [14]
    • Cell growth and differentiation [15][16]

Cellular and insulin-mediated uptake of glucose

The absorption time determines the onset, peak, and duration of effect. [17]

  • Prolonged insulin absorption time
    • Cold injection site
    • Obesity
    • Peripheral injection site
    • Superficial subcutaneous injection
  • Shorter insulin absorption time
    • Manipulative therapy (e.g., massages)
    • Deep subcutaneous injection
    • Injection into the abdominal skin around the navel

We list the most important adverse effects. The selection is not exhaustive.

Certain drugs can either increase or decrease insulin demand. [25]

Basal-bolus insulin regimen [2][3]

  1. Calculate the total daily dose of insulin (TDD) needed.
    • If the patient is already on a correction scale: Increase or decrease TDD by 10–20% as needed.
    • If the patient is lean, has T1DM, is aged ≥ 70 years, and/or has GFR < 60 mL/min: 0.2–0.3 units/kg
    • If none of the above criteria apply, use the blood glucose level:
      • BG 140–200 mg/dL: 0.4 units/kg
      • BG > 200 mg/dL: 0.5 units/kg
  2. Divide the TDD of insulin into basal insulin (50%) and nutritional insulin (50%).
    • Basal insulin: administer as long-acting insulin (e.g., glargine) at bedtime
    • Nutritional insulin: administer as rapid-acting insulin (e.g., lispro) in equally divided doses before meals
  3. Add sliding scale insulin as supplemental insulin.
    • Take 5% of the TDD (e.g., if the TDD is 50 units, 5% is 2.5).
    • Round down to the nearest whole number (e.g., round down 2.5 units to 2 units).
    • For every 40 mg/dL above the goal serum glucose of 140 mg/dL, increase the nutritional insulin scale by the appropriate increments (see “Sliding scale insulin regimen” below).
  4. Adjust as needed.
    • In cases of hypoglycemia < 70 mg/dL: Reduce basal insulin by 20% and/or sliding scale insulin by 2 units.
    • If glucose is persistently > 140 mg/dL and no episodes of hypoglycemia occur: Increase basal insulin by 20% and/or increase sliding scale insulin by 2 units.

Decrease or hold nutritional insulin if the patient is NPO.

Sliding-scale insulin regimen [3]

Administration of sliding scale insulin
Blood glucose (mg/dL) Insulin units
Insulin sensitive Usual insulin Insulin resistant
71–140 0 0 0
141–180 2 4 6
181–220 4 6 8
221–260 6 8 10
261–300 8 10 12
301-350 10 12 14
351-400 12 14 16

If blood glucose is < 70 mg/dL, hold all insulin and administer measures to control hypoglycemia.

Weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia [28]

  1. Convert glucocorticoid to equivalent prednisone dose (see “Glucocorticoids”).
  2. Calculate daily NPH dose based on prednisone dose equivalent and patient weight.
  3. Administer glucocorticoid with NPH as a single dose in the morning.
Prednisone dose equivalent (mg/day) NPH (units/kg/day)
10 0.1
20 0.2
30 0.3
≥ 40 0.4

NPH doses should be administered in addition to usual basal insulin in patients who are already receiving insulin.

Consider using glargine or detemir in patients receiving dexamethasone. Dexamethasone has a longer hyperglycemic effect than prednisone and most other commonly used systemic glucocorticoids.

Insulin regimens for enteral and parenteral nutrition

Enteral nutrition [29][30]

  1. Determine basal insulin needs.
    • For patients already on insulin: Continue prior dose or administer 30–50% of the total daily dose as long-acting insulin (e.g., glargine) daily.
    • For patients not already on insulin, consider:
      • 5 units of NPH every 12 hours
      • or 10 units of glargine (or equivalent) daily
  2. Add nutritional insulin.
    • For patients receiving continuous tube feedings
      1. Calculate the total daily nutritional insulin dose:
        • 1 unit of insulin per 10–15 g of carbohydrates per day
        • or 50–70% of the total daily dose
      2. Administer as rapid-acting insulin (e.g., lispro) in divided doses every 4–6 hours.
    • For patients receiving bolus feeding
      1. Calculate the nutritional insulin dose to cover each meal: 1 unit of insulin per 10–15 g of carbohydrates per meal
      2. Administer as rapid-acting insulin (e.g., lispro) before each feeding.
  3. Add sliding scale insulin as supplemental insulin.
  4. Adjust as needed to glycemic targets, changes in medication, and changes in nutrition.

Patients with type 1 diabetes mellitus require basal insulin even if (enteral) feeding is discontinued.

Total parenteral nutrition (TPN) [29][31]

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