Post-market Review Products Used in the Management of Diabetes Report to Government Stage 2: Insulin Pumps February 2015

2.4 Diagnosis

The current WHO (2006) diagnostic criteria for diabetes include:

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  Fasting plasma glucose ≥ 7.0mmol/l (126mg/dl); or
  
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  2–hour plasma glucose ≥ 11.1mmol/l (200mg/dl).
  

HbA_1c (glycated haemoglobin) is a laboratory test that shows the average level of blood glucose over the previous three months. HbA_1c has recently been accepted as an additional test to diagnose diabetes, provided that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values. An HbA_1c of ≥48 mmol/mol (6.5%) is recommended as the cut off point for diagnosing diabetes. However, a value less than 6.5% does not exclude diabetes, if a diagnosis of diabetes is indicated using the glucose tests above (WHO 2011).

2.5 Monitoring blood glucose and glycaemic control

2.5.1 Self-monitoring of blood glucose

Self-monitoring of blood glucose using blood glucose test strips and a blood glucose meter is recommended for people using insulin. In type 1 diabetes and gestational diabetes it is usually recommended that blood glucose levels be tested at least four times daily (early morning, plus other tests before and/or after meals). Less frequent testing in usually recommended for people with type 2 diabetes. Frequent consultation with health care professionals is important. Self-monitoring should be individualised and assist people with diabetes to understand the impact of insulin, food, physical activity, and other factors on blood glucose control. Frequency of monitoring should be determined according to the individual’s self-management goals.

2.5.2 HbA_1c

In addition to its use as a diagnostic tool, HbA_1c testing is also used to provide an indication of how well a patient’s diabetes is being controlled. High levels of HbA_1c indicate poor glycaemic control. The Diabetes Control and Complications Trial (DCCT) in Type 1 diabetes and the UK Prospective Diabetes Study (UKPDS) in Type 2 diabetes both showed that, as HbA_1c increases, the risk of microvascular and macrovascular complications of diabetes increases (Craig 2011).

The Australian Diabetes Society recommends a general target HbA_1c of ≤7.0% (53 mmol/mol) for most patients (Australian Diabetes Society 2009). However, HbA_1c targets should be individualised and may need to be higher for some people including children and the elderly (Craig 2011).

HbA_1c testing provides clinicians with a reliable indication that therapy is working appropriately and the risk of long-term complications, particularly microvascular complications, is reduced (Saudek & Brick 2009).

It should be noted that glycation of haemoglobin occurs only as the erythrocyte (red blood cell) circulates in serum. Therefore, anything that alters the erythrocyte survival will influence HbA_1c independent of glycaemia. In people with conditions associated with altered erythrocyte survival (e.g. thalassaemia, portal hypertension, haemolytic anaemia), HbA_1c is less reliable and self-monitoring of blood glucose or fructosamine testing, which measures the glycation of all serum proteins, may be of more value (Saudek & Brick 2009).

2.5.3 Glycaemic variability

Glycaemic variability has been suggested as a factor that may increase the risk of diabetes complications independent of HbA_1c. A systematic review examined glycaemic variability and its impact on diabetes complications and found that of eight studies in patients with type 1 diabetes, only two studies demonstrated a significant association with microvascular complications, and none showed an association with macrovascular complications (Nalysnyk 2010). Diabetes complications are proposed to result from increased mitochondrial oxidative stress induced by hyperglycaemia (Giacco & Brownlee 2010). One study showed that there was no association between glycaemic variability and urinary markers of oxidative stress in people with type 1 diabetes (Wentholt 2008). Though it remains uncertain, other studies also do not support glycaemic variability as an important independent factor in the development of diabetes complications in people with type 1 diabetes (Borg 2011, Cavalot 2013, Gordin 2008, Pena 2011). Therefore, due to this uncertainty, this report concentrates primarily on HbA_1c as a measure of glycaemic control and predictor of diabetes complications, and frequency of hypoglycaemic episodes as a measure of safety.

2.6 Treatment options and technologies for type 1 diabetes

People with type 1 diabetes are required to manage their condition with lifelong insulin therapy and blood glucose level monitoring. Insulin is administered subcutaneously where it is absorbed into the blood stream. The two main forms of insulin administration are the conventional method of multiple daily injections, and continuous subcutaneous insulin infusion using an insulin pump (insulin pump therapy) (Misso et  al. 2010).

2.6.1 Multiple daily injections

Multiple daily injection insulin therapy consists of administering around three or four insulin injections per day. There are five different types of insulin currently available to treat diabetes in Australia: ultra-short acting, short-acting, intermediate-acting, longacting, and pre-mixed. These types differ in both their speed of onset, time to peak, and duration of glucose-lowering action.

Ultra-short acting analogues and short-acting insulins are designed to supply the bolus level of insulin needed after a meal, while intermediate-acting insulin and long-acting analogues do not need to be injected with a meal and are used to help mimic the basal level of insulin excreted by the pancreas (Diabetes Australia 2008).

2.6.2 Insulin pumps

Insulin pumps are small, computerised, portable devices that deliver continuous, small doses of fast-acting insulin 24-hours a day, known as the basal insulin dose (Misso 2011). Basal insulin controls blood glucose at night and between meals (Diabetes Queensland 2009). A bolus dose, also of fast-acting insulin, is initiated manually by the individual before meals and when correcting hyperglycaemia (high blood glucose) (Diabetes Australia 2008).

Insulin is delivered through a small tube and cannula, and an infusion set inserted subcutaneously, usually in the abdomen or hip region (Misso 2011). These sets are changed on average every three days, depending on the type of infusion set.

Insulin dose adjustments may be based on food intake, exercise and other factors, and in-built algorithms may assist users with these calculations. The insulin pump can only be disconnected for short periods of time (for exercise or showering), usually not more than two hours (Diabetes Queensland 2009).

Insulin pumps do not measure blood glucose levels and levels must be monitored throughout the day with the use of blood glucose test strips and a blood glucose meter, similar to those using multiple daily injection therapy. Insulin pump users should perform four or more blood glucose tests a day to ensure insulin administration from the pump is correct. There are insulin pumps with the capability of continuous glucose monitoring with the addition of a glucose sensor (Diabetes Queensland 2009). However, continuous glucose monitoring does not replace the need for independent testing of blood glucose with a blood glucose meter, and for some insulin pumps is not indicated for use in patients under 18 years of age (Animas Corporation 2012; Medtronic MiniMed Inc. 2009).

2.6.3 Insulin pump use in Australia

The Australian Health Survey: Updated Results, 2011-12, indicates there are approximately 118,600 people with type 1 diabetes (ABS 2013). The AIHW report, Insulin Pump Use in Australia (2012b), states that there are approximately 10,510 people with type 1 diabetes in Australia currently using an insulin pump, or around 10% of all people with type 1 diabetes. It is unclear how the affordability of insulin pumps and the associated consumables influences their usage in Australia. However, the most commonly identified issue for insulin pump users in Australia, identified by 32% of survey respondents, was the cost of insulin pump consumables (AIHW 2012b).

Data from the NDSS indicates that in 2010 there were 10,285 children and adolescents aged between 0-18 years with type 1 diabetes in Australia (AIHW 2012a). NDSS data also indicates that almost one-third of people with type 1 diabetes aged under 20 years used an insulin pump (AIHW 2012b). Therefore, an estimated 3,400 people aged 0–18 years in Australia are using an insulin pump.

Insulin pump uptake in Australia is similar to the modelled uptake of insulin pumps in the United Kingdom, where the National Institute for Health and Clinical Excellence (NICE) estimated a 12.4% uptake across all age groups, and 33% uptake for those under 12 years of age (NICE 2009).

2.6.4 Diabetes management at school

For children using injections, the recommended treatment for type 1 diabetes usually involves four insulin injections a day, and therefore requires insulin administration at school. This raises questions as to whether children, particularly in early primary school, have the developmental capacity to self-administer insulin. Whilst children can be managed with two insulin injections a day, which eliminates the need for insulin administration at school, this treatment regimen is not considered ideal (Marks 2013). Children using insulin pump therapy would receive insulin continuously at a basal rate throughout the day, with additional bolus doses of insulin delivered via the pump at meal times or to correct high blood glucose levels. Bolus doses need to be programmed by the user.

The type of treatment and ability of a child to self-administer insulin at school may affect their treatment. A recent Australian study on children with type 1 diabetes attending kindergarten–year 2 (aged 4–8) found that children using insulin pump therapy were significantly more likely to receive insulin at school than those using injections (97% versus 55%). This may be because children who were able to self-administer insulin were more likely to receive treatment at school than those unable to self-administer (93% versus 65%), and children using insulin pumps were more likely to self-administer insulin than those using injections (63% versus 23%) (Marks 2014).

Attending school to assist with blood glucose testing and insulin administration can limit parents’ ability to work, leading to financial stress. An international survey showed that 46% of parents had to alter their work to manage their child’s diabetes at school (Lange 2009). As younger children may not have the ability to recognise the symptoms of hypoglycaemia or ask for assistance, this also poses a higher risk. One study indicated that 20% of parents were called to the school on a regular basis (Schwartz 2010).

In Australia, an unpublished study by Middlehurst and Morrison (2008) found that a parent attended school to assist with insulin administration in 28% of cases, most commonly for children using insulin injections and under the age of eight. After eight years of age most children administered blood glucose testing and insulin themselves. Teachers, school administration staff and nurses provided assistance with insulin administration in some cases, with teachers more willing to assist with administration through an insulin pump (as cited in Marks 2013). Also in Australia, Marks (2014) found that around 19% of children had insulin administered by a parent at school. Insulin injections at school were most commonly administered by the parent or child, while insulin delivered by an insulin pump was most commonly administered by the child, teacher or teacher’s aide. This research indicates that insulin pump therapy may improve diabetes treatment in young children at school and alleviate some of the pressure on carers.

2.6.5 New technologies

Continuous glucose monitoring devices consist of a glucose sensor that is inserted under the skin. They can be used in conjunction with a compatible insulin pump, and provide real-time monitoring of blood glucose levels throughout the day. Generally, glucose levels are displayed at 1-5 minute intervals. The devices can sound alarms to warn patients of impending hypoglycaemia or hyperglycaemia. Some pumps have the ability to suspend delivery of insulin once the sensor reaches a threshold of low blood glucose and sounds an alarm (Ly 2013).

Tubeless closed loop system insulin pumps consist of two components: a waterproof patch that holds and delivers insulin, and a device that connects wirelessly that programs insulin delivery and calculates insulin doses. It also features an in-built glucose meter.

The above sensor technologies are not currently funded by any Australian Government subsidy programme or through private health insurance. The pathway for new insulin pump technologies to request listing on the Prostheses List and associated reimbursement through private health insurers is to use existing Prostheses List Advisory Committee (PLAC) processes. These technologies will be assessed by the PLAC as applications are submitted by sponsors. Further information on PLAC and the Prostheses List is in Part 2.8.