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Insulin

Last updated: January 15, 2021

Summary

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.”

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 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).

Synthesis and regulation

Synthesis [4]

Insulin is produced and secreted from the β cells of the pancreatic islets.

Regulation [4]

The secretion of insulin is chiefly regulated by the levels of serum blood glucose.

Oral glucose results in a greater increase in insulin levels than IV administration.

Pharmacodynamics

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 [18]
    • Sodium retention by the kidney [19]
    • Ovarian androgen hypersecretion [20]
    • Decreased fibrinolytic activity [21]
    • Secretion of gastric acid [22]
    • Cell growth and differentiation [23][24]

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.”

Pharmacokinetics

The absorption time determines the onset, peak, and duration of effect. [25]

  • 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

Indications

Adverse effects

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

Pharmacologic and drug interactions

Certain drugs can either increase or decrease insulin demand. [33]

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 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 [36]

  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 [37][38]

  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) [37][39]

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References

  1. 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): p.16-38. doi: 10.1210/jc.2011-2098 . | Open in Read by QxMD
  2. 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): p.2181-2186. doi: 10.2337/dc07-0295 . | Open in Read by QxMD
  3. Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-Induced Hyperglycemia. Am J Med Sci. 2013; 345 (4): p.274-277. doi: 10.1097/maj.0b013e31828a6a01 . | Open in Read by QxMD
  4. American Diabetes Association. 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2018; 42 (Supplement 1): p.S173-S181. doi: 10.2337/dc19-s015 . | Open in Read by QxMD
  5. American Diabetes Association. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2017; 41 (Supplement 1): p.S144-S151. doi: 10.2337/dc18-s014 . | Open in Read by QxMD
  6. Gosmanov AR, Umpierrez GE. Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy. Curr Diab Rep. 2012; 13 (1): p.155-162. doi: 10.1007/s11892-012-0335-y . | Open in Read by QxMD
  7. Rorsman P, Braun M. Regulation of Insulin Secretion in Human Pancreatic Islets. Annu Rev Physiol. 2013; 75 (1): p.155-179. doi: 10.1146/annurev-physiol-030212-183754 . | Open in Read by QxMD
  8. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabetic Medicine. 2013; 30 (7): p.803-817. doi: 10.1111/dme.12159 . | Open in Read by QxMD
  9. Muscelli E, Mari A, Natali A, et al. Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab. 2006; 291 (6): p.E1144-E1150. doi: 10.1152/ajpendo.00571.2005 . | Open in Read by QxMD
  10. Winzell MS, Ahrén B. G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes. Pharmacol Ther. 2007; 116 (3): p.437-448. doi: 10.1016/j.pharmthera.2007.08.002 . | Open in Read by QxMD
  11. Prentki M, Madiraju SRM. Glycerolipid/free fatty acid cycle and islet β-cell function in health, obesity and diabetes. Mol Cell Endocrinol. 2012; 353 (1-2): p.88-100. doi: 10.1016/j.mce.2011.11.004 . | Open in Read by QxMD
  12. Nuttall FQ, Gannon MC, Wald JL, Ahmed M. Plasma glucose and insulin profiles in normal subjects ingesting diets of varying carbohydrate, fat, and protein content.. J Am Coll Nutr. 1985; 4 (4): p.437-450. doi: 10.1080/07315724.1985.10720086 . | Open in Read by QxMD
  13. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004; 287 (2): p.E199-E206. doi: 10.1152/ajpendo.00545.2003 . | Open in Read by QxMD
  14. Philippe J. Somatostatin Inhibits Insulin-Gene Expression Through a Posttranscriptional Mechanism in a Hamster Islet Cell Line. Diabetes. 1993; 42 (2): p.244-249. doi: 10.2337/diab.42.2.244 . | Open in Read by QxMD
  15. Brunton L. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition. McGraw-Hill Education / Medical ; 2017
  16. Kido Y, Nakae J, Accili D. The Insulin Receptor and Its Cellular Targets1. J Clin Endocrinol Metab. 2001; 86 (3): p.972-979. doi: 10.1210/jcem.86.3.7306 . | Open in Read by QxMD
  17. Ramnanan CJ, Edgerton DS, Rivera N, et al. Molecular Characterization of Insulin-Mediated Suppression of Hepatic Glucose Production In Vivo. Diabetes. 2010; 59 (6): p.1302-1311. doi: 10.2337/db09-1625 . | Open in Read by QxMD
  18. Philippe J. Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.. Proc Natl Acad Sci U S A. 1991; 88 (16): p.7224-7227. doi: 10.1073/pnas.88.16.7224 . | Open in Read by QxMD
  19. Fielding BA, Frayn KN. Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr. 1998; 80 (6): p.495-502. doi: 10.1017/s0007114598001585 . | Open in Read by QxMD
  20. Stralfors P, Bjorgell P, Belfrage P. Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin.. Proc Natl Acad Sci U S A. 1984; 81 (11): p.3317-3321. doi: 10.1073/pnas.81.11.3317 . | Open in Read by QxMD
  21. Jefferson LS. Role of Insulin in the Regulation of Protein Synthesis. Diabetes. 1980; 29 (6): p.487-496. doi: 10.2337/diab.29.6.487 . | Open in Read by QxMD
  22. DeFronzo RA, Felig P, Ferrannini E, Wahren J. Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am J Physiol. 1980; 238 (5): p.E421-E427. doi: 10.1152/ajpendo.1980.238.5.e421 . | Open in Read by QxMD
  23. Brands MW, Manhiani MM. Sodium-retaining effect of insulin in diabetes. Am J Physiol Regul Integr Comp Physiol. 2012; 303 (11): p.R1101-R1109. doi: 10.1152/ajpregu.00390.2012 . | Open in Read by QxMD
  24. Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome.. Fertil Steril. 1990; 53 (5): p.785-91.
  25. Juhan-Vague I, Alessi MC, Vague P. Thrombogenic and Fibrinolytic Factors and Cardiovascular Risk in Non-insulin-dependent Diabetes Mellitus. Ann Med. 1996; 28 (4): p.371-380. doi: 10.3109/07853899608999095 . | Open in Read by QxMD
  26. Polacek MA, Ellison EH. Insulin-Induced Stimulation of Gastric Acid Secretion. JAMA. 1963; 183 (12). doi: 10.1001/jama.1963.63700120009009c . | Open in Read by QxMD
  27. Sandhu MS. Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer. J Natl Cancer Inst. 2002; 94 (13): p.972-980. doi: 10.1093/jnci/94.13.972 . | Open in Read by QxMD
  28. Gunter MJ, Hoover DR, Yu H, et al. Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women. J Natl Cancer Inst. 2008; 101 (1): p.48-60. doi: 10.1093/jnci/djn415 . | Open in Read by QxMD
  29. Wallia A, Molitch ME. Insulin Therapy for Type 2 Diabetes Mellitus. JAMA. 2014; 311 (22): p.2315. doi: 10.1001/jama.2014.5951 . | Open in Read by QxMD
  30. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014; 383 (9922): p.1068-1083. doi: 10.1016/s0140-6736(13)62154-6 . | Open in Read by QxMD
  31. Rhee CM, Leung AM, Kovesdy CP, Lynch KE, Brent GA, Kalantar-Zadeh K. Updates on the Management of Diabetes in Dialysis Patients. Semin Dial. 2014; 27 (2): p.135-145. doi: 10.1111/sdi.12198 . | Open in Read by QxMD
  32. Morello C. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus. Int J Gen Med. 2011 : p.827. doi: 10.2147/ijgm.s26889 . | Open in Read by QxMD
  33. Insulin Drug Interactions. http://online.lexi.com/lco/action/home. . Accessed: October 28, 2020.
  34. Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen H-L, Rickels K. Antipsychotic-Induced Insulin Resistance and Postprandial Hormonal Dysregulation Independent of Weight Gain or Psychiatric Disease. Diabetes. 2013; 62 (9): p.3232-3240. doi: 10.2337/db13-0430 . | Open in Read by QxMD
  35. Tabata I, Schluter J, Gulve EA, Holloszy JO. Lithium Increases Susceptibility of Muscle Glucose Transport to Stimulation by Various Agents. Diabetes. 1994; 43 (7): p.903-907. doi: 10.2337/diab.43.7.903 . | Open in Read by QxMD
  36. McCall AL. Insulin Therapy and Hypoglycemia. Endocrinol Metab Clin North Am. 2012; 41 (1): p.57-87. doi: 10.1016/j.ecl.2012.03.001 . | Open in Read by QxMD
  37. Brown A, Guess N, Dornhorst A, Taheri S, Frost G. Insulin‐associated weight gain in obese type 2 diabetes mellitus patients: What can be done?. Diabetes Obes Metab. 2017; 19 (12): p.1655-1668. doi: 10.1111/dom.13009 . | Open in Read by QxMD
  38. Gentile S, Strollo F, Ceriello A. Lipodystrophy in Insulin-Treated Subjects and Other Injection-Site Skin Reactions: Are We Sure Everything is Clear?. Diabetes Ther. 2016; 7 (3): p.401-409. doi: 10.1007/s13300-016-0187-6 . | Open in Read by QxMD
  39. Hirshberg B, Muszkat M, Marom T, Muszkat M. Natural course of insulin edema. J Endocrinol Invest. 2000; 23 (3): p.187-188. doi: 10.1007/bf03343704 . | Open in Read by QxMD
  40. Herold G. Internal Medicine. Herold G ; 2014
  41. Le T, Bhushan V,‎ Sochat M, Chavda Y, Abrams J, Kalani M, Kallianos K, Vaidyanathan V. First Aid for the USMLE Step 1 2019. McGraw-Hill Medical
  42. 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): p.1119-1131. doi: 10.2337/dc09-9029 . | Open in Read by QxMD
  43. 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): p.363-70. doi: 10.4158/EP11260.OR . | Open in Read by QxMD