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  • Clinician

Insulin

Summary

Insulin is an anabolic peptide hormone that is produced and secreted from beta cells located in the islets of Langerhans of the pancreas. It has important metabolic functions, which include promoting the storage of carbohydrates, amino acids, and fat in the liver, skeletal muscle, and adipose tissues. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Insulin therapy is an important part of treatment for individuals with insufficient or absent insulin production (e.g., diabetes mellitus, gestational diabetes). Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure and differ in onset, peak, and duration compared to human insulin. 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.

For further information, see also insulin therapy and inpatient management of hyperglycemia.

Overview

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
  • 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

Rapid acting insulins leave no LAG - to remember Lispro, Aspart, Glulisine

Pharmacodynamics

  • Insulin is an anabolic peptide hormone; that is produced and secreted from beta cells in the islets of Langerhans of the pancreas in response to a rise in blood glucose
  • Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure; after injection they exert the same actions but differ in onset, peak and duration compared to human insulin
  • 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) and has the following actions:
Increases Decreases
Carbohydrate metabolism
Lipid metabolism
  • Lipid synthesis
Protein metabolism
  • Proteolysis
Other effects
  • Secretion of gastric acid
  • Cell growth and differentiation
  • Uptake of potassium

References:[4][5]

Adverse effects

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

Indications

Insulin regimens

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 total daily dose by 10–20% as needed.
    • If the patient is lean, has T1DM, age ≥ 70 years, and/or GFR < 60 mL/min: 0.2–0.3 units/kg
    • If none of the above criteria applies, 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 total daily dose of insulin into basal insulin (50%) and nutritional insulin (50%).
  3. Add sliding scale insulin as supplemental insulin.
    • Take 5% of the TDD (e.g., 50 → 2.5).
    • Round down to the safest whole number (e.g., 2.5 → 2).
    • For every 40 mg/dL (2.2 mmol/L) above the goal serum glucose of 140 mg/dL, increase the nutritional insulin scale by this increment.
  4. Adjust as needed.
    • If glucose persistently > 140 mg/dL and no episodes of hypoglycemia: Increase basal insulin by 20% and/or increase sliding scale insulin by 2 units.
    • In cases of hypoglycemia < 70 mg/dL: Reduce basal insulin by 20% and/or sliding scale insulin by 2 units.

Decrease or hold nutritional insulin if the patient is NPO.

Sliding scale insulin regimen [3]

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

Weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia [6]

  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 [7][8]

  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) [7][9]

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  • 1. Brunton L. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition. New York: McGraw-Hill Education / Medical; 2017.
  • 2. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Setting: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2012; 97(1): pp. 16–38. doi: 10.1210/jc.2011-2098.
  • 3. Umpierrez GE, Smiley D, Zisman A, et al. Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial). Diabetes Care. 2007; 30(9): pp. 2181–2186. doi: 10.2337/dc07-0295.
  • 4. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 5. Mantzoros C, Serdy S, Nathan DM, Mulder JE. Insulin Action. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/insulin-action. Last updated September 7, 2016. Accessed June 13, 2018.
  • 6. Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-Induced Hyperglycemia. Am J Med Sci. 2013; 345(4): pp. 274–277. doi: 10.1097/maj.0b013e31828a6a01.
  • 7. American Diabetes Association. 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2018; 42(Supplement 1): pp. S173–S181. doi: 10.2337/dc19-s015.
  • 8. American Diabetes Association. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2017; 41(Supplement 1): pp. S144–S151. doi: 10.2337/dc18-s014.
  • 9. Gosmanov AR, Umpierrez GE. Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy. Curr Diab Rep. 2012; 13(1): pp. 155–162. doi: 10.1007/s11892-012-0335-y.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
  • Le T, Bhushan V,‎ Sochat M, Chavda Y, Abrams J, Kalani M, Kallianos K, Vaidyanathan V. First Aid for the USMLE Step 1 2019. New York, NY: McGraw-Hill Medical.
  • Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. Diabetes Care. 2009; 32(6): pp. 1119–1131. doi: 10.2337/dc09-9029.
  • Shetty S, Inzucchi SE, Goldberg PA, Cooper D, Siegel MD, Honiden S. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol. Endocr Pract. 2012; 18(3): pp. 363–70. doi: 10.4158/EP11260.OR.
last updated 10/29/2020
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