Insulin Therapy

Insulin Therapy is one type of Treatment for Type 2 Diabetes. Prior to the discovery of insulin, children who developed type 1 diabetes typically died, often from diabetic comas. In diabetics, insulin is critical for avoiding major complications such as coma and death. Research has also shown that controlling glucose with insulin reduces other complications from diabetes such as neuropathy (nerve damage).^[1]

Insulin helps the body use sugar from the blood for energy. There is always some sugar in the blood. This means the pancreas needs to make small amounts of insulin all through the day. When you eat, your blood sugar goes up. This means the pancreas needs to make extra insulin during meals. When you are more active, your body uses more sugar and needs less insulin.

When you have diabetes, blood sugar stays high. Taking insulin shots is one way to treat diabetes. All insulin used to treat diabetes is made in a lab.

There are many different kinds of insulin. The kind you may need depends on your activity, eating habits, and how your body responds to insulin. Your doctor or nurse will work with you to match your needs with the kind of insulin that might work well for you.

Types of insulin

Main Article: Types of Insulin

Insulin that lasts all through the day

There are two kinds of insulin that can control blood sugar all through the day. They are intermediate-acting and long-acting insulin. Both kinds give a constant, low level of insulin all through the day. Usually this means one or two shots a day.

Insulin that lasts all through the day:

Insulin for meal times

After time, one kind of insulin may not be enough to control blood sugar. Your doctor or nurse may add insulin that is used at meal times. There are two kinds of insulin that control blood sugar at meal times. They are fast-acting and short-acting insulin. These kinds of insulin work quickly and last for a short period of time. They cover the high blood sugar from eating a meal. This can mean taking two or more shots a day.

Insulin for Meal Times:

Premixed insulin for all day and meals

Some people with diabetes need both kinds of insulin. They need insulin that lasts all through the day and insulin for meal times. Premixed insulin combines both kinds of coverage. It gives you quick coverage for a meal plus longer coverage for other times of the day. If you take premixed insulin, you may need fewer shots each day.

There are different types of premixed insulin.

• Premixed NPH/regular insulin is made by combining NPH and regular insulin.
• Newer premixed insulin is the other type of premixed insulin. It is made by combining insulin aspart (NovoLog®) or insulin lispro (Humalog®) with a longer lasting insulin made only for the mix

Insulin that covers both (all through the day and meal times):

Risks

Complications

Insulin can cause hypoglycemia (low blood sugar) and hypokalemia (low blood potassium). Some patients develop sensitivity to some forms of insulin (this is more common when using insulin extracts from animals than when using synthetic insulin). This may cause itching and redness at the site of injection, or as a more serious reaction characterized by rash over the entire body, wheezing, shortness of breath, and other symptoms, including anaphylactic.^[2]

Lipodystrophy also occurs.

Worsening of diabetic retinopathy, diabetic neuropathy, or diabetic nephropathy are common complications. This can happen when high blood sugar remains elevated over a long time (months to years) as a result of insufficient insulin dosage.

Interactions

Many medications may increase the need for insulin. Some of these medications are corticosteroids, isoniazid, niacin, estrogens, and thyroid replacement therapy, such as Synthroid.

Other drugs decrease insulin needs. These include oral antidiabetes drugs , sulfa antibiotics, beta-blockers, and alcohol.^[2]

Abuse

Some athletes who abuse growth hormone to enhance their performance also use insulin to increase the effects of growth hormone.^[3]

Overdose

Overdose of insulin causes hypoglycemia (low blood sugar). This can be mild, or it can lead to seizures, coma, and impaired brain and nerve function. Death can occur if the blood sugar is very low, and stays low for a long time without treatment. ^[2]

Precautions

All forms of insulin can cause severe hypoglycemia (low blood sugar). This occurs at different times following the use of insulin, depending on the form used. Close monitoring of blood sugar while using insulin is necessary.

Adjustment of insulin doses around mealtimes is important.

Patients with poor kidney function may need to adjust their doses of insulin.^[2]

Side Effects

• Hypoglycemia is the most common side effect that may occur during insulin therapy. Symptoms of hypoglycemia include confusion, nausea, hunger, tiredness, perspiration, headache, heart palpitations, numbness around the mouth, tingling in the fingers, tremors, muscle weakness, blurred vision, cold temperature, excessive yawning, irritability, and loss of consciousness.

• Blurred vision may occur if blood sugar levels are elevated for a prolonged period of time and return to normal too rapidly with aggressive treatment. This is due to a shift of fluid within the lens of the eye. In time, vision returns to normal.

• Skin reactions include redness, swelling, itching or rash at the site of injection.

• Changes in body fat distribution (lipodystrophy), which usually happens at the injection site. It can be minimized by varying the site of injection.

• Allergic reactions

• Sodium retention

• General body swelling

How Insulin Is Taken

The central problem for those who use insulin as a medication is picking the right dose and the right timing. How quickly or slowly insulin works in the body depends on several factors:

• A person's response to insulin
• The site of injection on the body
• The type and amount of exercise that is done and the length of time between the shot and exercise
• When a person has last eaten

Timing of administration

Most people with type 1 diabetes mellitus need at least two insulin shots a day for good blood glucose control. Some people take three or four shots a day to have adequate coverage. If regular insulin is taken alone or with a longer-acting type, insulin should be taken 30 minutes before a meal. If a rapid-acting insulin is taken, the insulin should be taken just before eating.

After a short time, people typically get to know when the insulin starts to work, when it reaches its peak concentration, and when it finishes working. Mealtimes and exercise times should be scheduled to match the time each insulin dose is taken.

Routes of administration

Intravenous

This form of insulin is reserved for people who have dangerously high blood sugar levels and are at risk for (or already have) diabetic ketoacidosis. Usually, these people have type I diabetes. Intravenous insulin is used only in the hospital, and is commonly referred to as an insulin "drip."

Subcutaneous

Pre-filled insulin syringe ("insulin pen"). Source: Wikimedia Commons.

Insulin is usually taken as subcutaneous injections using single-use syringes with needles, an insulin pump, or repeated-use insulin pens with needles. Administration schedules attempt to mimic the physiologic secretion of insulin by the pancreas. Hence, both a long-acting insulin and a short-acting insulin are typically used.

Insulin can be injected into several places on the body. Insulin injected near the stomach works fastest. Insulin injected into the thigh works slowest. Insulin injected into the arm works at medium speed.

Insulin pump

Main Article: Insulin Pump

Insulin pumps are a reasonable solution for some. Advantages include better control over background or basal insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that help with determining bolus infusion dosages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes (excessively low or high blood sugar), catheter problems, and no means of easily controlling insulin delivery based on current blood sugar levels.

Inhalation

Inhaled insulin has similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals. An injection of long-acting insulin at night is often still required. Studies suggest that inhaled insulin is no more effective than injected insulin and that its cost is prohibitively high for most people, which limits its benefit.^[4]

Following inhalable insulin's commercial launch in 2005 in the UK, it was not (as of July 2006) recommended by National Institute for Health and Clinical Excellence for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist".

In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin. It was withdrawn from the market in 2007, due to lack of acceptance.

In January 2008, the world's largest insulin manufacturer, Novo Nordisk A/S, also announced that the company was discontinuing all further development of the company's own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly, Eli Lilly and Company ended its efforts to develop its air inhaled insulin in March 2008.

Transdermal

There are several methods for transdermal delivery of insulin. Pulsatile insulin uses microjets to pulse insulin into the patient, mimicking the physiological secretions of insulin by the pancreas. Jet injection (also sometimes used for vaccinations) has different insulin delivery peaks and durations as compared to needle injection. Some diabetics find control possible with jet injectors, but not with hypodermic injection.

Both electricity using iontophoresis and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of wrist appliances is commercially available.

Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin.

Intranasal insulin

Intranasal insulin is being investigated. A recent clinical trial demonstrated the expected rise in plasma insulin concentrations and fall in plasma glucose after administration, but not all of the insulin was absorbed, and the amount absorbed varied considerably from person to person. ^[5]

Oral insulin

The basic appeal of oral agents for controlling blood sugar is that most people would prefer a pill to an injection. However, insulin is a protein, which is digested in the stomach and gut. In order to be effective, scientists have not yet found a way to deliver insulin orally. The oral hypoglycemic agents [such as Glucophage (]metformin) and Actos (pioglitazone) that are used by some type 2 diabetics do not contain insulin.

Alternative Devices for Taking Insulin

See Alternative Devices for Taking Insulin

Research

Newer varieties of rapid-acting insulin now in Phase II clinical trials are designed to work rapidly. They retain the same genetic structure as regular human insulin.

The potential market for an oral form of insulin is assumed to be enormous. Many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein (near the liver) to have a measurable effect on blood sugar. As of 2004, no products appear to be successful enough to bring to market.

A Connecticut-based company called Biodel, Inc. is developing what it calls VIAtab, an oral formulation of insulin designed to be taken sublingually. This therapy is a tablet that dissolves in minutes when placed under the tongue. In a Phase I study, VIAtab delivered insulin to the blood stream quickly and resembled the first-phase insulin release spike found in healthy individuals. The company claims that an oral insulin therapy would be more convenient than currently available injectable or inhalable therapies. They expect this convenience to result in increased insulin usage among currently underserved early-stage patients with Type 2 diabetes, thus helping to create better long-term outcomes for that patient population.

Australian biopharmaceutical company, Apollo Life Sciences, plans to enter the Phase I trial of its oral insulin tablet in mid-2008.

An Israeli pharmaceutical company, Oramed Pharmaceuticals, is currently conducting Phase IIA studies on an oral insulin pill.