Revisiting Insulin Therapy

Whether you are in the Medical Ward, Surgical, Theatre or in the Emergency setting; in the Laboratory, Pharmacy or in your office as a dietitian, you may in one way or the other had come across Insulin. Today on Clinical Hints, let’s use few minutes of our time to recap our knowledge on Insulin therapy.
Insulin plays a very vital role in the regulation of carbohydrate, fat, and protein metabolism. Clinically, insulin is indicated for Patient with Type 1 diabetes, some Type 2 diabetes Patients: during periods of physical and emotional stress such as infection and surgery, when oral antidiabetic drugs are contraindicated or when other methods of controlling blood sugar have failed.
 
Insulin may also be used in acute situations such as Diabetic Ketoacidosis (DKA)- more common with Type 1 Diabetesand Hyperosmolar Hyperglycemic Nonketotic Syndrome – more common with Type 2 Diabetes.In rare cases, insulin therapy may also be initiated in severe hyperkalemia (elevated serum potassium levels) even in patients without diabetes.
 
Primarily, the therapeutic goal of insulin therapy is to move glucose across cell membranes especially in the skeletal muscle and fat tissue and also inhibit the liver from changing glycogen to glucose.
 

Sources

Currently there are five sources of Insulin: pork pancreas, beef pancreas (beef insulins are now rarely used), pork-beef mixtures; human sequence insulin may be produced semisynthetically by enzymatic modification of porcine insulin or biosynthetically by recombinant DNA technology using bacteria or yeast. Theoretically, human insulin should be associated with a much lower incidence of allergic reaction but no real advantage has been shown in trials.
 

How Insulin Circulate In The Body

Insulin is always injected because when taken orally, the GI tract breaks down the protein molecule before it reaches the bloodstream. All insulins, however, may be given by subcutaneous (subQ) injection. Absorption of subQ insulin varies according to the injection site, the blood supply, and the degree of tissue hypertrophy at the injection site. It is necessary to rotate the site of administration because of local irritation and fat accumulation at site of injection. The usual sites for injection are the upper lateral aspect of the thighs, the deltoid area of the arms, the abdomen, or the upper back: lateral to the spinal cord. Nurses must keep a chart or help the client prepare a chart that changes the location of the injection site every day.
 
Regular insulin may also be given by I.V. infusion as well as in dialysate fluid infused into the peritoneal cavity for patients on peritoneal dialysis therapy.
 
Insulin preparations are stable for considerable periods of time at room temperature. The vial in use should be kept at room temperature and any additional supply refrigerated and protected from strong light. Insulin must be at room temperature (but without heating) before injection. Injection of cold insulin can lead to lipodystrophy, reduced rate of absorption and local reactions.
 
Also, the preparations that are suspensions (usually the intermediate and long acting insulin – remember some short acting insulins are also suspensions) should be mixed thoroughly by rotation and inversion before the dose is withdrawn. Shaking the preparation is ill-advised, as it causes foaming.
 
After absorption into the bloodstream, insulin is distributed throughout the body. Insulin-responsive tissues are located in the liver, adipose tissue, and muscle. It is metabolized primarily in the liver and to a lesser extent in the kidneys and muscle, and it’s excreted in stool and urine.
 
Excessive insulin action leads to hypoglycaemia and in the extreme, the coma of insulin shock. Also in few clients, local allergic reactions may occur which usually manifest as urticarial, pruritis and redness of the area of injection. When allergic reactions occur, the client is switched to a preparation derived from a different species than the one that caused the allergic response.

Insulin Preparations

The principal difference among the various insulin preparations, and the major factor in choice of drug, is duration of action. Insulin preparations can be divided into 3 types:
 
  • ·         Those of short duration which have a relatively rapid onset of action, namely soluble insulin and the rapid-acting insulin analogues: insulin aspart, insulin glulisine, and insulin lispro.
  • ·         Those with an intermediate action, e.g. isophane insulin and
  • ·         Those whose action is slower in onset and lasts for long periods, e.g. protamine zinc insulin, insulin detemir, and insulin glargine

The duration of action of a particular type of insulin varies considerably from one patient to another, and needs to be assessed individually. Also, note that, mixtures of insulin preparations may be required to achieve a particular effect. For example short acting insulin may be mixed with intermediate acting insulin or given concomitantly.
 

1.      Short-Acting Insulin

1.1  Soluble Insulin

Soluble insulinis a short-acting form of insulin. It is usual to inject it 15 to 30 minutes before meals. Soluble insulin is the most appropriate form of insulin for use in diabetic emergencies e.g. diabetic ketoacidosis and at the time of surgery. It can be given intravenously and intramuscularly, as well as subcutaneously.
 
When injected subcutaneously, soluble insulin has a rapid onset of action (30 to 60 minutes), a peak action between 2 and 4 hours, and duration of action of up to 8 hours. When injected intravenously, soluble insulin has a very short half-life of only about 5 minutes and its effect disappears within 30 minutes.
 
Examples include Hypurin Bovine Neutral, Hypurin Porcine Neutral, Actrapid, Humulin S, Insuman Rapid
 

1.2       The Human Insulin Analogues

The human insulin analogues: insulin aspart, insulin glulisine, and insulin lisprohave a faster onset and shorter duration of action than soluble insulin; as a result, compared to soluble insulin, fasting and preprandial blood-glucose concentrations are a little higher, postprandial blood-glucose concentration is a little lower, and hypoglycaemia occurs slightly less frequently.
 
Examples include NovoRapid (Insulin Aspart), Apidra (Insulin Glulisine), Humalog (Insulin Lispro)


2.      Intermediate and Long-Acting Insulin

When given by subcutaneous injection, intermediate and long-acting insulins have an onset of action of approximately 1–2 hours, a maximal effect at 4–12 hours, and a duration of 16–35 hours. Some are given twice daily in conjunction with short-acting (soluble) insulin, and others are given once daily, particularly in elderly patients.
 
Examples of Intermediate: Hypurinc Porcine Isophane, Humulin I
 
Examples Long-Acting: Lantus
 

BIPHASIC INSULINS (MIXED PREPARATIONS)

Soluble insulin can be mixed with intermediate and long-acting insulins (except insulin detemir and insulin glargine) in the syringe, essentially retaining the properties of the two components, although there may be some blunting of the initial effect of the soluble insulin component (especially on mixing with protamine zinc insulin).
 
Examples Include: NovoMix 30, Mixtard 30, Insuman Comb 15
 
Biphasic insulins have different combinations and thus must not be replaced with another unless otherwise specified. Novomix 30 is entirely different from Mixtard 30 though they all contain mixtures of short acting and intermediate acting and thus must not be replaced with another. Whereas Novomix 30 contain 30% insulin aspart, 70% insulin aspart protamine, Mixtard 30 contain 30% soluble, 70% isophane.
 
Even preparations with similar brand names may still be different and must not be replaced with another, unless otherwise indicated. For instance, whereas Insuman Comb 15 contain 15% soluble, 85% isophane, Insuman Comb 25 contain 25% soluble, 75% isophane. Prescribers, Nurses and Patient must stick to one brand type unless well convinced (medically informed) before a switch.


Summary

Insulin therapy remains a vital tool in the management of conditions such as Diabetes Melitus and its related complications. A good understanding of its mode of action and effect will help improve client outcomes.

Written By Prince Assandoh-Mensah (RN, BSN- CHN, Clinical Nurse)

 

REFERENCES

Berman, Audrey.Kozier, Barbara. (Eds.) (2008) Kozier & Erb’s fundamentals of nursing :concepts, process, and practice Upper Saddle River, N.J. : Pearson Prentice Hall
 
Billiodeaux, S. T., Samuelson C. G., Fox C. G. (2014). Intraoperative and Postoperative Blood Glucose Concentrations in Diabetic Surgical Patients Receiving Lactated Ringer’s Versus Normal Saline: A Retrospective Review of Medical Records. The Ochsner Journal. Ochsner Clinic Foundation
 
Brandel, R. L. (2015). Ringer’s  Lactate  vs.  Normal  Saline  in the  pre-hospital  protocols. Isotonic, hypertonic, hypotonic fluids, when, why, and where  are  they primarily used? NREMT Rappahannock Community College, Fall  2015, EMS  209  –  Advanced Pharmacology
 
Daksha, J. (2013). Comparison of the use of normal saline versus Ringer`s lactate in the fluid resuscitation of diabetic ketoacidosis. URI: http://hdl.handle.net/10539/12476
 
Hinkle, J. L. (2014). Brunner & Suddarth’s textbook of medical-surgical nursing (Edition 13.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
 
Joint Formulary Committee. (2008). British national formulary 73. London: BMJ Publishing and the Royal Pharmaceutical Society
 
Rajamani, S., Selvarajan, K. P. & Radhakrishnan, S. (2017). A Comparative Study between Ringer Lactate, Normal Saline and Plasmalyte on the Serum Electrolytes of Patients with Diabetic Ketoacidosis. Indian Journal of Medical & Health Sciences.  Volume  4, Issue 1, January – June 2017, Pages 23-29
 
Simpson AK, Levy N, Hall GM. Peri-operative i.v. fluids in diabetic patients—don’t forget the salt. Anaesthesia. 2008 Oct;63(10):1043–1045. [PubMed]
 
Swonger, AK., Matejski MP. (1991). Nursing Pharmacology: an integrated approach to drug therapy and nursing practice. J.B. Lippincott Company, Philadelphia
 
Thomas DJ, Alberti KG. Hyperglycaemic effects of Hartmann’s solution during surgery in patients with maturity onset diabetes. Br J Anaesth. 1978 Feb;50(2):185–188. [PubMed]
 
Walsh ES, Traynor C, Paterson JL, Hall GM. Effect of different intraoperative fluid regimens on circulating metabolites and insulin during abdominal surgery. Br J Anaesth. 1983 Feb;55(2):135–140. [PubMed] [Ref list]
 
Wilson, B.A., Shannon, M.T., & Stang, C.L. (2005). Prentice Hall Nurse’s Drug Guide 2005. Upper Saddle River NJ. Pearson Education Inc.,
 

 

Van Zyl, D. G., Rheeder. P., & Delport. E. (2012). Fluid management in diabetic-acidosis–Ringer’s lactate versus normal saline: a randomized controlled trial. QJM. 2012 Apr;105(4):337-43. doi: 10.1093/qjmed/hcr226. Epub 2011 Nov 22  
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