The miracle treatment: insulin

Insulin has been available for a century and has gone from poorly defined animal insulin to pure and precisely controlled formulations. Dr Louise Johnson tells us more about this miracle treatment.

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History of insulin

The discovery of insulin, the miracle treatment, is attributed to a group at the university of Toronto, Canada. In 1922, a 22-year-old physician, Frederick G Banting, worked in a laboratory to test his idea that pancreas extracts will reduce blood glucose levels in diabetic dogs. Banting was assisted by a student, Charles Best. This led to the first successful test of insulin in a 14-year-old boy, Leonard Thompson.

In January 1922, this boy with diabetes received the first dose of purified animal insulin and his life was saved. Leonard Thompson lived another 13 years to be 27 years and he passed away due to bronchopneumonia.

What is insulin?

Insulin is a hormone produced by the beta cells of the pancreas called the islet cells of Langerhans, in a response to reduce blood glucose. It works on cellular level to allow sugar to enter each cell by opening a channel in the cell. Glucose enters the cells and is used inside the cell to produce energy. The organs that are highly insulin dependent are the muscle, liver and fat.

Who needs insulin?

All living creatures needs insulin for uptake of glucose to be used as a source of energy.

Insulin is the primary treatment for people living with Type 1 diabetes since they have no endogenous or own insulin. They were previously called insulin-dependent diabetes mellitus (IDDM).

People with Type 2 diabetes, previously called non-insulin-dependent diabetes mellitus (NIDDM), also requires insulin at some time during their disease. As time progresses, the amount of the beta cells of the pancreas diminish and a supplementation with once-daily insulin, called basal insulin, is needed.

In Type 2 diabetes with insulin resistance where more insulin is needed, supplementation would also be required. The treatment of Type 2 diabetes always included diet, exercise, metformin, other antidiabetic agents such as incretins, SGLT2 inhibitors and sulphonylureas. When the HbA1c is above 7.5% on these regimens’ insulin supplementation is needed.

How do miracle treatment injections work?

Insulin is injected in the subcutaneous fat layer (just beneath the skin) on the abdomen, upper thigh, arm and buttocks. Once injected in the subcutaneous layer, it’s not immediately absorbed in the bloodstream. The insulin molecule first dissociates into dimers and monomers before being absorbed.

Insulin initiation

Patients with Type 1 diabetes require insulin immediately and usually multiple daily dosages to cover both mealtime and sleeping glucose levels. This regime is called basal-bolus insulins.

The preferred method on insulin initiation in Type 2 diabetes will be to add a once-daily long-acting insulin when needed. If glucose targets are not met, then a mealtime insulin or bolus insulin will be added according to the need.

Types of insulin

1. Basal insulin therapy
2. Bolus insulin therapy
3. Premixed insulin
4. Concentrated insulin
5. Inhaled insulin

1. Basal insulin therapy

Manipulating various side chains of the insulin molecule has permitted availability of long-acting insulin, such as glargine, determir and degludec (Lantus, Basaglar, Optisulin, Toujeo, Tresiba).

These long-acting insulins are peak less with a long duration of action. Basal insulin slows the production of glucose from the liver. In a fasting state this will maintain glucose homeostasis.

In general, basal insulin is administered once-daily in 24-hour cycle at the same time every day. It’s important that basal insulin should always be administered regardless of food intake as this serves as the background insulin normally secreted by the pancreas.

NPH insulin (Protophane) is one of the oldest basal insulin and because of its shorter lifespan needed to be injected twice a day. It has been available since 1964. The primary advantage of NPH is financial as it is typically less costly than the newer long-acting insulins. The downside of NPH is that it does make a small peak which can lead to hypoglycaemic events.

2. Bolus insulin therapy

Bolus insulin is rapid-acting insulin that can be given before meals to reduce mealtime peaks of sugar. The combination of basal and bolus insulin is a flexible regime.

The newer short-acting insulins are called analogues (Novorapid, Apidra, Humalog, FiAspart). Analogues differ from human preparation (regular insulin) by small substitutions in amino acid chains which in turn prevent formation of polymers or hexamers.

The onset and peak action of rapid-acting insulin analogues more closely resemble endogenous (own) human insulin secreted in response to a meal.

Due to the fact that it is rapid-acting insulin, it can be given before, during or directly after a meal. The mealtime dosage of insulin can be calculated according to the amount of carbohydrates in the meal. Patients with a varying appetite can increase, decrease or omit the mealtime insulin according to the carbohydrates in the meal.

3. Premix insulin

Premix insulin preparations is a combination of short-acting and intermediate/long-acting insulin in a fixed ratio. Although this provides convenience for some and may be appealing to those who refuse to inject more than twice a day, it does not allow for flexibility in mealtime or changes in the ratio of short to long-acting insulin doses.

An example is Novomix which is a fix combination of 70% NPH (protophane) and 30 % Novorapid. Another example is Ryzodeg which is a combination of 70 % degludec (Tresiba) and 30% insulin aspart (Novorapid). The numbers expressed in the ratio after the insulin refer to the percentage of insulin in the premix solution. An example is Humalog 25 which has 75 % long-acting and 25% short-acting insulin.

4. Concentrated insulin

Insulin that is two to three times more concentrated than the normal U 100 insulin is now available. The available concentrated insulin in South Africa is glargine U300 (Toujeo).

The positive effect of more concentrated insulin is that the volume that is needed to inject is smaller in patients that are severe insulin resistant and need high volume insulin.

Humalog U500 is a short-acting concentrated insulin that is available on special request in severe insulin resistant patients that need more that 200 units per day.

5. Inhaled insulin

The least often used preparation is human insulin inhalation powder (Alfrezza), however this is not available in South Africa. It’s administered at the beginning of a meal. Lung function must be assessed before initiation and after six months and thereafter yearly. It’s contraindicated in patients with lung disease and asthma.

Insulin sliding scale

Although commonly utilised in hospitals when patients are acutely ill, it’s not recommended as a routine method of insulin management. The reason for this is that it causes extreme fluctuations of glucose values which are far worse than continuous slightly elevated blood glucose. The best method to use short-acting insulin is via carbohydrate counting before meals.

Side effects of the miracle treatment

Hypoglycaemia

The most severe side effect is hypoglycaemia. It’s important that all diabetic patients on medication know how to treat the symptoms of low blood sugar. Usually if glucose is below 4.0 mmol, 15 gram of carbs is indicated. This can be in the form of a small fruit juice.

It’s important that all diabetic patients on insulin have a glucagon hypo kit at home for their spouse or parent to administer should the patient not respond. Always recheck the glucose after an episode of hypoglycaemia and try to establish the cause. If hypoglycaemia occurs frequently speak to your doctor for a thorough evaluation.

Weight gain

It was clearly shown in the UKPDS study that patients on insulin gain 5 to 8kg over a 10-year period. To prevent weight gain, try to limit carbohydrates and prevent hypoglycaemia. Should you pick up weight speak to your doctor. Remember that underactive thyroid disease can be associated with diabetes.

Lipodystrophy

Lipodystrophy is hardened fat tissue. This happens when you are injecting on the same place every time and it causes poor insulin absorption. To prevent this from happening, it’s important to rotate the injection sited daily

Insulin has now been available for 100 years and this miracle treatment for diabetes has saved many lives and prevents many complications if used correctly. Remember that insulin is not the enemy but in persons with diabetes, it’s your best friend.

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