Insulin

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.”

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

Insulin function and metabolic effects

• Insulin binds to insulin receptors (a type of tyrosine kinase receptor) located in various tissues in the body (e.g., liver, skeletal muscle, adipose tissue, cell membranes). ^[4]
• In target tissues, insulin acts as an anabolic hormone.

• 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

• Glucose may enter cells throughout the body via a variety of transporters.
• Different tissue types have unique glucose transporters (e.g., GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5), some of which are insulin-dependent and some of which are insulin-independent.
• See “Important glucose transporters” in "Carbohydrates.”

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

• Type 1 diabetes mellitus ^[2]
• Type 2 diabetes mellitus ^[18][19]
  • Indicated if weight normalization, physical activity, and oral antidiabetic drugs do not keep blood glucose levels in the target range.
  • Patients with end-stage renal failure should have doses of insulin titrated according to the glomerular filtration rate. ^[20]
• Exocrine pancreatic insufficiency with secondary diabetes
• Gestational diabetes mellitus
• Acute hyperkalemia: A drip containing regular insulin and a solution of glucose reduces blood potassium levels.
• See “Insulin therapy” in “Diabetes mellitus” and “Inpatient management of hyperglycemia.”

• Hypoglycemia ^[21]
• Weight gain ^[22]
• Lipodystrophy at the injection site ^[23]
• Hypokalemia
• Allergic or hypersensitivity reactions
• Edema ^[24]
• Pain and erythema at the injection site

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

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

• Increased insulin demand
  • Thiazide diuretics and loop diuretics
  • Heparin
  • Glucocorticoids
  • Immunosuppressive drugs (e.g., calcineurin inhibitors)
  • Tricyclic antidepressants
  • Antipsychotic drugs ^[26]
  • Lithium ^[27]
  • HIV-protease inhibitors
  • Thyroid hormones
  • Estrogen (contraceptives)
  • Sympathomimetic drugs that interact with the β₁-adrenergic receptor (e.g., dobutamine)
  • Derivatives of nicotinic acid
• Decreased insulin demand
  • Analgesics (e.g., NSAIDs, tramadol)
  • Antibiotics (e.g., cotrimoxazole and other sulfonamides , fluoroquinolones)
  • Antimalarial drugs (e.g., mefloquine, quinine)
  • MAO inhibitors
  • Fibrates
  • Haloperidol
• Either increased or decreased insulin demand
  • Ethanol
  • Beta blockers

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]

• If the patient is eating all or most of each meal: Administer as short-acting insulin (or rapid-acting insulin) before each meal and at bedtime.
• If the patient is not eating: Administer as short-acting insulin every 6 hours.

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.

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.

• One-Minute Telegram 11-2020-1/3: Quality over quantity: once-weekly insulin

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