What is insulin?
Insulin is a hormone secreted from beta cells of the pancreas. It helps to control the blood glucose levels preventing hyperglycemia (high glucose levels) which can damage the cells. In diabetes mellitus (sugar diabetes), there may be a lack of or deficiency of insulin thereby leading to abnormal fluctuations in blood glucose levels and hyperglycemia. Insulin exerts its effects by binding to insulin receptors present on the cell surface of organs sensitive to insulin like liver, muscles and fat tissue. The binding of insulin to its receptors results in activation of an enzyme known as tyrosine kinase which leads to reactions inside the cell that are responsible for various effects of insulin.
Actions of Insulin
Insulin influences growth and metabolism in a variety of tissues and therefore has a number of different effects in the human body. This occurs over seconds, minutes, hours and days. The effects of insulin are as follows:
- Reduces blood glucose levels by :
- Stimulating glucose transport from the blood into cells, particularly muscle and fat cells.
- Stimulating synthesis of glycogen (storage form of glucose).
- Inhibiting breakdown of glycogen into glucose.
- Inhibiting glucose synthesis from protein and fats (gluconeogenesis) in the liver.
- Enhances tissue growth by :
- Preserving protein and fat by preventing glucose synthesis from these compounds.
- Stimulating fat (triglyceride) synthesis in the liver, fat storage in adipose tissue and also inhibits breakdown of stored fat.
- Regulating transcription of several genes which is needed for production of various amino acids.
- Promoting cell proliferation and therefore tissue growth.
The effects on blood glucose levels occurs within seconds and minutes while on tissue growth it happens over hours and days.
Sources of Insulin
Insulin is obtained from different sources namely :
- bovine (beef)
- porcine (pig)
- human (recombinant)
The recombinant human insulin is widely preferred over the other types because of its minimal immune (allergic) reactions. The porcine insulin is less likely to cause allergic reactions compared to the beef insulin. Beef insulin products have been discontinued in the US. The recombinant human insulin is obtained either from cultures of genetically modified bacteria or yeast. In some South American countries guinea pig insulin was in use, but proved to be less effective than bovine or porcine insulins.
Types of Insulin
There are various types of insulin preparations with different properties. These preparations are developed with minor modifications of the amino acid sequence of insulin and addition of non-insulin components to preparations. The insulin preparations are traditionally classified into groups based on duration of action (how long it acts) and onset of action (how quickly it starts acting). The different types of insulin preparations are :
- Ultra short-acting
- Ultra long-acting
Ultra short-acting insulins
The ultra-short acting insulin effects last only for 4 to 5 hours and hence the name. Its effects are seen very rapidly, usually with in 15 to 30 minutes following subcutaneous injections. These preparations therefore need to be taken only immediately before the meals. It is preferred because it is less likely to cause a very drastic drop in blood glucose levels (severe hypoglycemia) and night time dips in glucose levels (nocturnal hypoglycemia).
The short-acting insulins effects last for 8 to 12 hours but takes 45 to 60 minutes to start acting. It should be given subcutaneously 30 minutes to 1 hour before meals. Short-acting insulins can also be given intravenously in case of diabetic emergencies like diabetic ketoacidosis.
Intermediate-acting insulins has an effect for 12 to 18 hours. It dissolves gradually after subcutaneous injection and is absorbed slowly from the injection site. This accounts for its rather slow action.
Long-acting insulins have duration of action lasting for 18 to 24 hours. It is used once or twice daily to provide background insulin throughout the day and is combined with ultra short or short-acting insulins.
Ultra long-acting insulins
These insulin preparations continue acting for more than 24 hours. It takes about 1 to 2 hours to start acting. In type 2 diabetic patients, the ultra long-acting insulins can be used in combination with oral antidiabetic drugs while in type 1 diabetics it may be used with short acting insulins.
The dose of insulin is expressed in units. Majority of standard commercial preparations are available as solution or suspension of 100 units/mL concentration. Some regular insulin preparations are also available at 500 units/mL concentration for use in patients requiring larger insulin doses.
The amount of insulin required daily to maintain the near normal levels of glucose is referred as the daily insulin requirement. It varies with body weight and health status. A normal, healthy non-obese individual requires 0.2 to 0.5 units per kg per day (18-20 units/day). Requirement in type 1 diabetic patients varies from 0.2 to 1 units per kg per day. Average insulin requirement in obese type 2 diabetic patients is about 2 units per kg per day.
Insulin is usually administered by subcutaneous injections. It may be taken subcutaneously in the abdomen, the front of thigh, the buttocks, or the arm. The injection sites are ideally rotated for better response and reduce some side effects. All insulins require refrigeration and the insulin should be brought to room temperature, before it is injected. The longer acting insulins are given only subcutaneously. Insulin absorption from subcutaneous injection sites varies with the type of insulin, blood flow, temperature at injection site and exercise.
The different methods of insulin administration includes :
- Continuous subcutaneous insulin infusion (CSII) are infusion pumps that deliver subcutaneous insulin continuously and are an alternative to multiple daily injections.
- Jet injection systems are available to give needleless subcutaneous insulin injections. It provides painless insulin injection option for some patients.
- Intravenous (IV) insulin is reserved for acute diabetic emergencies like diabetic ketoacidosis.
- Inhalable insulin is inhaled in a powder form into lungs. It has been withdrawn from US market.
- Intranasal insulin is sprayed into the nasal cavity.
The video below illustrates the proper insulin injection technique.
Side Effects of Insulin
Low Glucose Levels
The most common and most important complication of insulin therapy is hypoglycemia. This is a state where the blood glucose levels drop very low. Hypoglycemia can occur with inappropriately high insulin dose, incorrect timing of insulin administration or food intake, unusually strenuous physical activity after taking insulin injection or inadequate carbohydrate intake. When this happens while a person is awake, then the early warning signals can be identified (hypoglycemia awareness) and corrected. However, if it arises at night (nocturnal hypoglycemia) then these warning signs may be missed although a person may report night sweats and headaches upon waking. Symptoms of hypoglycemia includes :
- increased heart rate (tachycardia)
If the hypoglycemia is corrected at this point, then it will not progress any further. However, chronic diabetics may lose this awareness and this can lead to severe hypoglycemia. Attacks of severe hypoglycemia may present as :
- difficulty concentrating
- abnormal behavior
- blurred vision
Severe hypoglycemia treatment involves administering glucose orally or intravenously. Glucagon may be used in severe cases where intravenous glucose is not possible.
Subcutaneous insulin can produce allergic reactions in some individuals but such reactions are rare with use of recombinant human insulin. Most frequent allergic reactions are IgE-mediated local cutaneous reactions (skin rash), but very rarely it may be severe enough to cause anaphylactic reactions. Anti-insulin IgG antibody formation and subsequent insulin neutralization may happen in some patients treated with insulin of animal origin.
The impure animal insulins that were used previously were responsible for the majority of immune reactions related to insulin and the highly purified porcine and human insulin currently used are much less antigenic than the older insulins. The allergic reactions may still occur in some patients due to reactions to the presence of small quantities of denatured insulin or minor contaminants. It can also result as an immune response to non-insulin component of insulin formulations.
Skin rashes may develop as a result of allergic reactions discussed above. In addition, repeated injections of insulin at same site can lead to lose of smooth contour of the skin. This results from atrophy (shrinking) or hypertrophy (enlarging) at the injection sites causing dimples or bumps on the skin. The atrophy is believed to result from an immunogenic response to certain non-insulin components in insulin preparations. Hypertrophy is due to the growth promoting action of insulin in fat tissues causing uneven accumulation of fat at the site (lipodystrophy). A traditionally recommended solution to prevent both the complications is to rotate the site of insulin injection.
Insulin pump therapy can have some unique problems. Ketoacidosis can develop rapidly if therapy is interrupted accidentally by pump failure, needle dislodgement or infusion catheter kinking. Most of the modern pumps currently used have warning devices that can detect such failures. Subcutaneous cellulitis and abscesses are also possible with insulin pumps.
Lungs and breathing
Inhaled insulin was associated with bronchospasm, recurrent respiratory tract infection, and it was withdrawn following a suspected link to lung cancer.
Some patients with severe hyperglycemia who are controlled with insulin can develop abdominal bloating, edema and blurred vision. Some patients also show a certain degree of weight gain with insulin therapy.