The great power of insulin

As we celebrate the centenary of insulin therapy, Dr Angela Murphy reflects on what a change it has made in the management of diabetes. It’s a life-saving medication.

A telegram to Dr Robert Lawrence: “I’ve got insulin – it works – come back quick.”

In May 1923, Dr Robert Lawrence was in Florence, Italy, far from his family home in Scotland, preparing to die from Type 1 diabetes.  A telegram from his colleague urged him to return to London and on 31 May 1923, Lawrence received his first injection of insulin. His life was saved! Lawrence went on to become a leading diabetologist and help found the British Diabetes Association. He lived almost 50 productive years thanks to insulin.

Present day

Yet today, insulin is frequently not seen as life-saving but rather as a harbinger of the end of the road. People with Type 1 diabetes require insulin injections from diagnosis as they lose the ability to secrete insulin from the beta-cells in the pancreas.

In Type 2 diabetes, insulin deficiency only develops after several years.  A healthy lifestyle, as well as oral medications, is prescribed to bring glucose levels under control. It’s important to remember that diabetes is, by nature, a progressive disease.

Initial treatments aim to improve insulin sensitivity and improve endogenous insulin secretion. At some point, the insulin secreting cells of the pancreas struggle to keep up with demands and start to shut down. When glucose control can’t be achieved with the body’s own insulin then it’s time to start insulin injections.

Incredibly, sometimes this seems to trigger a partial recovery of some beta-cells. It turns out that they had not died, merely gone on strike as the work became too hard. When reinforcements arrive in the form of an insulin injection, they decide to return to work. This is the reason people with diabetes often manage with just one injection daily, in combination with their tablets, for many years.

How does insulin work?

Insulin is needed to open the glucose channel into the cell so that glucose from the blood can enter the cell. If there is not enough insulin, or the cell resists the action of the insulin, blood glucose levels will rise.

In the 1920s, insulin was derived from animals and only lasted in the body for several hours. In the 1950s, modifications were made to allow the insulin to be absorbed more slowly into the body. Over the next decades more advances where made with the introduction of human insulin, insulin analogues, improved delivery devices (pens and pumps) and non-injectable insulin (not available in SA). However, the precept of the purpose of insulin has not changed: it functions to move glucose from the blood into the cells where glucose is used to produce energy.

Patients often ask me how the morning blood glucose can be high when they have not eaten for 10 hours. Glucose enters the body directly from food and from stored glucose in the liver and muscle, particularly the liver. In the fasting state, such as being asleep overnight, the liver not only releases stored glucose but also manufactures glucose. One of the earliest features of insulin resistance occurs when the production of glucose in the liver is not kept in check, resulting in a rise in fasting glucose. At this point people with diabetes may be advised to start a night-time insulin.

Insulins available in SA

With such a plethora of insulins on the market, it’s no wonder insulin use can seem overwhelming and confusing. To better understand how the different insulins are used, I will explain the various insulin regimens that people with diabetes may be started on.

BASAL INSULIN

Regular insulins: Humulin N; Protophane; Biosulin N

Analogue Insulins: Basaglar; Levemir; Lantus and Optisulin; Tresiba; Toujeo

Most people with diabetes who are initiated on insulin will start with one daily injection, usually at bedtime. The efficacy of this insulin is determined by the fasting blood glucose reading: i.e. the blood glucose measured on waking in the morning before eating or drinking. If this fasting blood glucose is not at the target range (see Table 2 for your target range as per our South African guidelines), then the evening insulin is adjusted accordingly. The important points about bedtime insulin dose adjustment are:

  • Adjustments are NOT made according to the bedtime glucose
  • Adjustments are made according to the average fasting blood glucose values over a 3-7-day period (your HCP will determine this time frame).

Thus, adjustments are not made up and down daily. Rather they are based on the trend of the averages. Sometimes, the HCP may suggest using the basal insulin twice daily if they feel it would benefit daytime control. The titration of the morning dose will then be determined by the evening glucose reading, as explained below in the Pre-Mix Insulins.

TABLE 2: Target range (2017 SEMDSA GUIDELINES)

HbA1c FBG (mmol/L) PPG (mmol/L)
YOUNG <6.5% 4-7 <8
MOST <7,0% 4-7 <10
ELDERLY <7,5% 4-7 <12

TWICE DAILY PRE-MIX INSULIN

Regular insulins: Actraphane; Humulin 30/70; Insuman; Biosulin 30/70

Analogue insulins: NovoMix 30; Humalog Mix 25; Humalog Mix 50; Ryzodeg

When good glucose control can’t be maintained throughout the day with tablets alone, then insulin must be given to allow glucose absorption from meals. Pre-mix insulin consists of a mixture of short and intermediate insulin in the same pen. Some important points to remember:

  • This insulin will replace the basal insulin.
  • It’s essential to remember that a pre-mix insulin must be given BEFORE meals. I have often come across patients switched from basal to premix insulin and continued to give the evening insulin dose before bedtime, i.e. several hours after supper. This is extremely dangerous as the short-acting component can cause low blood glucose during the night.
  • Adjusting the dose of pre-mix insulin can seem quite complex. As with basal insulin, this must be done according to trends and not according the reading on hand.
  • The dose of morning insulin is determined by how well the glucose readings are controlled during the day, so we look at the pre-dinner reading to decide.
  • The dose of the evening insulin is determined by the control of glucose overnight, so we use the morning reading to decide (similar to titrating basal insulin).

Insulin diary log

I ask my patients to keep a diary and send it in every week so that I can help with these dose adjustments until we have reached the target glucose levels.

BASAL BOLUS INSULIN

Basal insulins as described above.

Bolus insulins:

Short-acting regular insulins: Humulin R; Actrapid; Biosulin R

Rapid-acting analogue insulins: Humalog; NovoRapid; Apidra

This regimen aims to mimic the normal function of the pancreas: intermediate or long-acting insulin provides the background insulin needed and then short-acting insulin is given before each meal (but not with snacks).

This short-acting insulin can be adjusted at every injection according to the pre-meal glucose reading and food being eaten. People with diabetes on this regimen are often taught carbohydrate counting. This is a method of quantifying how much carbohydrate is in a meal.

The HCP works out a ratio of insulin dose per carbohydrate portion and this is calculated at each meal. In addition, high glucose readings need to be corrected, so people with diabetes are taught a correction formula to bring the blood glucose back to an average of 6mmol/l (see calculation below). This sounds much more complicated than it is.

With some practice, people with diabetes can use this skilfully. It’s mainly used in Type 1 diabetes but is appropriate for anyone using a basal bolus regimen.

CALCULATION OF A BOLUS INSULIN DOSE

Pre-meal dose of insulin = food dose + correction dose, where

Food dose = (total carbohydrate portion) ÷ carbohydrate insulin ratio

Correction dose = (blood glucose – 6) ÷ sensitivity factor

The carbohydrate insulin ratio and sensitivity factor will be provided by the healthcare provider.

Constant communication with doctor

At my practice, we would not expect patients with diabetes to adjust their own insulins in those first weeks. They are asked to send readings in regularly, weekly to begin. We often revert to recording the readings the old-fashioned way with a diabetic diary as seen above and the patient can email or text that to me or the diabetic nurse educator (DNE). Some patients are using newer glucometers with Apps that can be uploaded and sent in.

HbA1c readings

Overall diabetes control is assessed with an HbA1c measurement every three to six months. HbA1c is a complex of glucose attached to haemoglobin in the red blood cell. This allows us to see what the average glucose is over the previous three months and gives a more comprehensive idea of control compared to the glucometer.

If the HbA1c and glucometer readings don’t correlate, then we must look at where in the day the blood glucose is increasing. To do this, patients will be asked to do 360’ testing or seven-point profile testing. For three days, they must test before and two hours after each meal as well as before going to bed (seven readings). This can help decide the next step in insulin management.

Getting the best response from insulin therapy

Up to this point, emphasis has been made on the choice of insulin and finding the correct dose. However, it’s important to remember the following when aiming to get the best response from insulin therapy:

  1. Timing of the insulin injection
    1. Basal insulin should be given at the same time every day. There is only a leeway of an hour either way.
    2. Pre-mix insulin should be given 30 minutes BEFORE breakfast and dinner.
    3. Bolus insulin should be given 15-30 minutes BEFORE each meal. No insulin will work in time if given at or after the meal.
  2. Changing of needles used to inject insulin should be done every THIRD injection. If looked at under a microscope after three injections, the needle has a barb on it and can cause significant trauma to the skin and subcutaneous tissue.
  3. Rotation of sites is essential. Repeatedly using the same site will result in a condition called lipohypertrophy, the accumulation of fat at the injection site causing a lump.

If your healthcare provider suggests it’s time to start insulin, do not see this as a negative in your diabetes journey but as a tool to continue in good health in your life journey.

MEET THE EXPERT


Dr Angela Murphy is a specialist physician working in the field of Diabetes and Endocrinology in Boksburg. She is part of the Netcare Sunward Park Bariatric Centre of Excellence and has a busy diabetes practice.


Insulin pump therapy in SA

Dr Louise Johnson gives us a breakdown of the insulin pump therapy available in South Africa.


Diabetes is rapidly becoming a major health epidemic in most regions of the world. All Type 1 diabetes patients and a significant number of Type 2 diabetes patients require the use of insulin for controlling blood glucose.

There are several varieties of insulin and many different injection regimes that can be used. Despite the availability of insulin vials and pens, the acceptability for patients and the glucose readings that are obtained with single or multiple injections regimens is not to the desired level.

This is where insulin pump therapy also known as continuous subcutaneous insulin infusion (CSII) comes in.

Continuous subcutaneous insulin infusion

Insulin pumps were introduced half a century ago. They utilise short- or rapid-acting insulin types only. This minimises variability of administration and reduces the chances of glucose fluctuations. Pump therapy has progressed to the level of mimicking physiological demands.

Pumps are programmed to deliver basal or background insulin. This is usually the same as the previous long-acting insulin. Basal insulin delivery happens automatically. It delivers a programmable dosage per hour every 24 hours; it’s tailored according to the glucose profile of the person.

The insulin requirements may be affected by a person’s physiology, exercise, work schedule, concomitant medications, and illness.

Most patients utilise multiple basal rates over a 24-hour period. There are some that only uses one rate. Most pumps have the capability of programming basal rates that can be used in special situations as a temporary basal rate. Your physician will determine all this.

There is also a bolus function. This is calculated according to the carbohydrate ratio used for carb counting. The person should administer the correct amount of total carbohydrates consumed to the pump and it will then automatically calculate the exact number of insulin and deliver it. This will be administered over minutes to a few hours. Insulin boluses cover meals and correct high blood glucose levels.

How is insulin delivered?

This happens via a plastic cannula connected to the pump on the one side and a single subcutaneous site with a connection on the other side.

The subcutaneous site is the same as a person would inject insulin in the fat tissue on the abdomen. The site needs to be changed every three to four days to prevent infection or inflammation.

Only rapid-acting insulin can be put into a pump. Usually the analogues work best (Novorapid, Humalog and Apidra).

Advantages

  1. Programmable insulin delivery allows closer match with physiologic needs.
  2. Uses only short- or rapid-acting insulin. This minimises peaks and absorption related variability.
  3. Use one injection site every three to four days. This reduces variation in absorption and treatment burden from multiple injections.
  4. Reduction in glucose variability and improve glucose control.
  5. Decrease the risk of severe hypoglycaemia
  6. Improved quality of life and treatment satisfaction.

Type 1 ideal candidate

The ideal candidate for initiation of pump therapy is a motivated patient who is knowledgeable in the important aspects of diabetes self-care and desires better glucose control.

The patient should be familiar with carbohydrate counting and have knowledge about pump technology.

However, a pump is neither a cure for diabetes nor does it function autonomously without intervention or input.

Patients should be clear about the fact that the pump is a highly-specialised gadget. It requires constant interaction from the wearer.

It’s important to regular monitor blood glucose and communicates with a professional pump team. This will predict long-term success.

Indications for insulin pump therapy

  1. Suboptimal glucose control despite multiple daily injections. You do not reach your target HbA1c.
  2. Frequent or unpredictable hypoglycaemia and hypoglycaemia unawareness.
  3. Dawn phenomenon. That is the early rising of blood glucose between 2am and 8am.
  4. An active lifestyle with strenuous physical activities.
  5. Children and young adults who typically desire fewer restrictions and more flexibility.
  6. Growth spurt of adolescents.
  7. Preconception planning and pregnancy
  8. The presence of gastroparesis. (Abnormal slow movement of food from stomach to the rest of the bowel).
  9. Hectic lifestyle with frequent travel between time zones.
  10. Shift work.
  11. Need for flexibility in the amount and timing of meals.
  12. Patients that are sensitive to insulin and need very small dosages.
  13. Type 2 diabetes patients with increased insulin requirements.

Types of pumps in South Africa

We currently have three different companies with have a variety of pumps. Each have its own pros and cons. It’s important that your medical team is familiar with your pump. Medical aids sometimes prefer to pay for certain pumps.

Medtronic 780 G is the newest of the Medtronic pumps and is a hybrid close loop system.

Tandem T slim 2 is the newest of the Tandem pumps and is also a hybrid close loop system pump.

Roche Accucheck Combo is a traditional pump.

Understanding hybrid close loop pump systems

In this type of system, the insulin pump “talks” to a continuous glucose sensor. The pump has a built-in algorithm; this allows the insulin to increase or decrease according to the blood glucose to attain the target. The only interaction the patient has with the pump is the input of carbohydrates consumed. Currently this is the ‘top’ pump to have if possible.

Disadvantages

  • Pumps are technology and they can break or malfunction
  • Cannulas can kink and this will stop insulin delivery.
  • Infusion sites can get infection or inflammation. This will cause rapid development of extreme hyperglycaemia, especially in Type 1 diabetes patients.

Pumps are not yet perfect but they are very close to it. Safeguards, such as alarms that warn of delivery problems or low amount of insulin in the pump reservoir are now standard features of insulin pump.

Dr Louise Loot

MEET THE EXPERT


Dr Louise Johnson is a specialist physician passionate about diabetes and endocrinology. She enjoys helping people with diabetes live a full life with optimal quality. She is based in Pretoria in private practice.