Understanding the role of insulin in the management of type 1 diabetes

Insulin regimens

There are three main types of insulin regimen used by people with diabetes: basal-bolus, biphasic and continuous subcutaneous infusion. People with type 1 diabetes typically use basal-bolus or continuous subcutaneous infusion regimens; biphasic regimens are not usually recommended, unless the patient is unable to adhere to the other regimens (also see: “The role of insulin in the management of type 2 diabetes”).¹

Basal-bolus regimens use a short-acting insulin injected before or with meals and snacks and an intermediate/long-acting (basal) insulin injected once or twice daily. A variety of short-acting and basal insulins are available fully subsidised (Table 1). Basal-bolus insulin regimens are usually administered as a flexible dose but some patients may use a fixed dose, depending on their circumstances. Flexible dose regimens are adapted to the carbohydrate content of upcoming meals (see: “A brief “how to” guide for carbohydrate counting”), thereby allowing more freedom with meal timing and food choices, and reducing the risk of hypoglycaemic episodes if there are changes to the daily schedule, e.g. exercise.³ People using fixed-dose regimens, e.g. if they are unable to count carbohydrates, must regulate their carbohydrate intake and ensure that it is distributed across the day to match their insulin regimen to prevent hypoglycaemia.³

Continuous subcutaneous infusion regimens use a short-acting insulin delivered by a pump (available fully subsidised with Special Authority approval – see below) in small doses over 24 hours, i.e. a basal rate, with boluses delivered at meal times. This replaces the need for an intermediate or long-acting insulin. This regimen most closely matches normal endogenous basal-bolus insulin release.⁴ The basal rate is programmed to fit the individual’s changing insulin requirements across the day. The bolus doses are adjusted for carbohydrate content of the upcoming meal; patients enter the information into the pump and it calculates the insulin dose. Correction doses can also be administered between meals if blood glucose levels are high.

Further information for primary care providers on insulin pumps is available from the PHARMAC seminar series on the PHARMAC NZ YouTube channel: https://www.youtube.com/watch?v=uE4Y3Hpvb_M and https://www.youtube.com/watch?v=zN2MYy1LxAg

Short-acting insulin

There are four fully subsidised types of short-acting insulins available in New Zealand (see Table 1 for brand names and product variations). Insulin aspart, insulin glulisine and insulin lispro (also called rapid-acting insulin analogues) have a faster onset and shorter duration of action than human neutral insulin (a recombinant insulin identical to human insulin) and have been associated with fewer hypoglycaemic episodes and lower post-prandial blood glucose levels in some studies.⁵ The rapid-acting insulin analogues can be used in insulin pumps^*; human neutral insulin is not recommended for use in pumps due to the risk of precipitation in the catheter or needle.³ There are no clinical differences in the onset or duration of action between the different rapid-acting insulin analogues.²

Most people with type 1 diabetes who use a basal-bolus regimen use a pen device for insulin administration. There is some variability in the pens provided by different manufacturers which may make one preferable to another, e.g. maximum number of doses, whether they deliver insulin in half-unit increments, size of the dial, pressure needed on the injection button to deliver the dose.⁶

^* Only insulin aspart and insulin lispro should be used in subsidised pumps

For a schematic representation comparing the duration of action of different insulins, see: www.nzf.org.nz/nzf_3629

Basal insulin

Basal insulin is administered once or twice daily to mimic normal basal insulin secretion. There are two types of basal insulin available fully subsidised in New Zealand (see Table 1 for brand names and product variations):

• Isophane insulin, also known as NPH^* insulin, is an intermediate-acting insulin
• Insulin glargine, an insulin analogue, is a long-acting insulin

A long-acting insulin is the first choice for most patients with type 1 diabetes, however, there may be some circumstances where patients are initiated on isophane insulin, e.g. renal failure.

For further information on initiating basal insulin in people with type 2 diabetes, see: www.bpac.org.nz/2019/hba1c.aspx

^*Neutral Protamine Hagedorn (NPH); the name refers to neutral pH, protamine (a protein), and Hans Christian Hagedorn (an insulin researcher)

Strategies to reduce the risk of insulin dosing errors

There are many steps in an insulin regimen where potential errors can occur. Strategies to minimise these risks include:^7,8

• Using the selected insulin with the appropriate delivery device, e.g. cartridge, disposable pen
• Using a short-acting and basal insulin from the same manufacturer as the patient will be familiar with the delivery system, e.g. Novorapid and Protaphane (Table 1)
• Ensure the needle length is appropriate; most people with type 1 diabetes use 4 mm length needles
• Writing out the word “units” in full
• Prescribing insulin using the full brand name; taking care when prescribing and dispensing products with similar names, e.g. Humalog, Humalog Mix and Humulin; Novomix and Novorapid

Table 1: Subsidised short, intermediate and long-acting insulins³

^*All funded insulin formulations are at a concentration of 100 units/mL. Three months’ supply may be dispensed at one time if endorsed “certified exemption” by the prescriber

^†Injection syringes and pen needles may be prescribed with subsidy if prescribed on the same form as insulin or if the patient has previously had a prescription of insulin and the prescription is endorsed; pharmacists may endorse the prescription if there is a prior record of insulin dispensing¹⁰

Insulin pumps

In New Zealand, insulin pumps and consumables, i.e. insulin cartridges/reservoirs and infusion sets are fully subsidised for patients who meet criteria for Special Authority approval (see below). Pump use is much higher among young people; in 2016, approximately one-quarter of people aged under 20 years were using an insulin pump compared to approximately 8–10% of people aged 20–60 years.¹¹ There is also a disparity in the use of insulin pumps by ethnicity; pump use is at least two-fold higher in New Zealand Europeans with type 1 diabetes compared to Māori, Pacific and Asian peoples.¹¹ Ensure that eligible patients are aware of the availability of fully subsidised insulin pumps; this technology can be beneficial for people of all ages, provided they have the appropriate support, training, commitment to monitoring and cognitive capacity.

Insulin pumps replace the need for multiple daily injections, thereby eliminating one of the burdens of diabetes management, however, patient education and adherence are critical for treatment to be successful. Clinical trials comparing insulin pumps with multiple daily injection regimens have reported improved HbA_1c levels, reductions in hypoglycaemia and higher patient satisfaction with pump use.² When functioning optimally, use of an insulin pump is associated with lower rates of diabetic ketoacidosis, however, adverse events such as pump malfunction or problems with the infusion sets are not uncommon and can lead to diabetic ketoacidosis if the malfunction and hyperglycaemia are not detected.² Pump users may become de-skilled in managing a multiple daily injection regimen which can cause problems if they need to return to injections for any reason.

Insulin pumps do not eliminate the need for blood glucose testing; pump users need to test frequently to optimise their insulin regimen. More frequent testing, including during the night, is necessary when first establishing the appropriate basal insulin requirements. Continuous glucose monitoring can make this easier, however these devices are not subsidised in New Zealand (see: “Continuous and intermittent [flash] glucose monitoring”).

Patients must meet specific criteria to be eligible for a fully subsidised insulin pump

People with type 1 diabetes may be eligible for a subsidised insulin pump under one of the following categories:

• HbA_1c, i.e. has unpredictable and variable blood glucose levels; average HbA_1c ≥ 65 mmol/mol to ≤ 90 mmol/mol
• Severe unexplained hypoglycaemia, i.e. has had four severe unexplained hypoglycaemic episodes in six months; average HbA_1c is ≥ 53 mmol/mol to ≤ 90 mmol/mol
• Previous use before 1 September, 2012, i.e. people who were already using a pump before they became publicly funded

N.B. People with permanent neonatal diabetes (appears in the first six months of life), cystic fibrosis-related diabetes or who have undergone a pancreatectomy are also eligible to apply for a subsidised insulin pump.

Within each of these categories there are a number of other criteria that the patient must meet, e.g. have undertaken carbohydrate counting education, be under the management of a multidisciplinary team, adhered to a multiple daily injection regimen for more than six months. Patients enquiring about insulin pumps in general practice should be given information and referred to their diabetes team in secondary care for further discussion. The initial Special Authority applications for the pump and consumables must be made by a diabetes specialist or diabetes nurse practitioner.

The Special Authority approval for insulin pump consumables must be renewed every two years; general practitioners often apply for these renewals. The Special Authority entitles patients to a prescription for a three-month supply of:

• Infusion sets (three boxes)
• Insulin cartridges/reservoirs (three boxes)

Patients can also be prescribed one extra box of infusion sets and cartridges/reservoirs each year (to cover possible equipment failure), but this must be listed on a separate prescription from their usual three-monthly supply.

Be sure when prescribing that the right product is selected so the correct items are ordered and provided by the pharmacy, i.e. the Paradigm consumables for the MiniMed 640G pump and the Autosoft 30 or TruSteel consumables for the Tandem t:slim X2 pump. Also confirm the patient’s cannula preferences (steel or teflon; straight or angled; length), line length and whether they need an autoinjector. See the NZF for further information: www.nzf.org.nz/nzf_70437

The Special Authority criteria for a subsidised insulin pump is available here: https://schedule.pharmac.govt.nz/ScheduleOnline.php?osq=Insulin%20pump

Best practice tip: Remind patients who use an insulin pump to have a back-up kit, including short- and intermediate/long-acting insulin, syringes/pens, blood glucose and blood ketone meters with test strips and information on their total daily basal insulin dose and ratios (insulin to carbohydrate and correction), so that they can convert back to a multiple daily injection regimen if necessary, e.g. pump failure, civil emergency.⁴

Self-monitoring blood glucose levels

People with type 1 diabetes need to regularly monitor their blood glucose levels to adjust their insulin dose or carbohydrate intake to prevent hyper- and hypoglycaemia. For many people this is achieved by finger prick testing using blood glucose test strips and a handheld blood glucose meter. People with type 1 diabetes are eligible for any of the four CareSens meters that are available fully subsidised (Table 3); one of these, the CareSens Dual meter, measures both blood glucose and blood ketone levels and is only available for people with certain conditions, including those with type 1 diabetes.³

N.B. Prescribers can also order meters on a PSO.

Table 3: Subsidised blood glucose meters and eligibility criteria.³

Monitor blood glucose at least four times per day

All adults with type 1 diabetes should be encouraged to test at least four times per day, i.e. before each main meal and before bed; testing before bed and before breakfast are the most important for detecting and preventing nocturnal hypoglycaemia.¹ Additional testing, e.g. up to 10 times per day, may be indicated in situations such as:^1,12

• If the desired HbA_1c target has not been achieved
• If the frequency of hypoglycaemic episodes increases
• If hypoglycaemia is suspected or after treating hypoglycaemia
• Before critical tasks, e.g. driving^*
• During periods of illness
• Before, during (if possible) and after exercise
• Pregnancy and breastfeeding:
  • Poor glycaemic control at conception and during early pregnancy increases the risk of congenital malformations, miscarriage, stillbirth and neonatal death
  • The risk of hypoglycaemia is increased during pregnancy and breastfeeding

Blood glucose levels should be recorded in a log book or using a smartphone app. The recommended blood glucose targets for people aged > 18 years with type 1 diabetes are:¹

• Pre-breakfast: 5.0–7.0 mmol/L
• Pre-lunch or dinner: 4.0–7.0 mmol/L
• Post-meal: 5.0–9.0 mmol/L (at least 90 minutes after eating)

^*People with type 1 diabetes need to be aware of the restrictions and requirements for driving; information from the New Zealand Transport Agency is available here: www.nzta.govt.nz/assets/resources/factsheets/16/docs/16-diabetes.pdf

Continuous and intermittent (flash) glucose monitoring

Continuous (i.e. glucose readings are reported automatically at regular intervals) glucose monitors and intermittent, or “flash”, glucose monitors (i.e. the patient scans the sensor to get a reading) detect and report glucose levels in the interstitial fluid through a subcutaneous sensor, largely replacing the need for routine finger prick testing.^2* The high frequency of measurements made by continuous glucose monitoring devices, e.g. every 5–15 minutes, can help to optimise insulin treatment by providing more detailed information about an individual’s blood glucose profile throughout the day and night.² Some devices also have an alarm feature which will alert the patient to the risk of hyperglycaemia or hypoglycaemia;² this can help reduce anxiety about blood glucose monitoring and hypoglycaemia, particularly at night. Data from a continuous or intermittent glucose monitor can be accessed through the reader or a smartphone app, allowing patients more convenient and discrete monitoring of their blood glucose levels.²

Continuous and intermittent glucose monitors are not subsidised in New Zealand, therefore cost is likely to be the limiting factor for most patients considering this technology. For example, one of these devices costs approximately $90 for the reader and $90 for the sensor, which needs to be replaced every two weeks. Continuous and intermittent glucose monitors must be purchased directly from the manufacturer or their New Zealand distributor.

^* Devices may require finger prick testing for calibration; finger prick testing is also still indicated in certain circumstances, e.g. if blood glucose levels are changing rapidly, if hypoglycaemia is reported by the device, if symptoms do not match the reading from the device.¹³

Patient information on intermittent glucose monitors is available from: www.diabetes.org.nz/news-and-update/2018/3/7/news-children-free-from-pain-of-routine-finger-pricks-with-revolutionary-diabetes-sensing-technology