Insulin pump therapy
In health, insulin is continuously secreted by the pancreas, with sharp spikes in response to food and a relatively constant basal rate between meals. Injected insulin cannot match this constant background rate of secretion, despite improvements in formulation of longer-acting insulin. Continuous infusion of rapid-acting insulin under the skin approximates more closely to physiological insulin secretion. The first infusion systems were introduced in the 1970s, and the following decades saw rapid technical progress in terms of compact lightweight pumps that are easy to wear and to use, improved delivery systems, malfunction alarms and techiques for avoidance of subcutaneous infections. Pumps are only as safe and effective as the people who use them, and the best results are obtained at specialized pump centres with well-established education and support systems. They are generally reserved for people who are unable to achieve stable control with standard therapy, for those who are highly motivated to achieve optimal near-normoglycaemia, and for those with unpredictable patterns of work, such as junior doctors. Pump systems are the generally "open loop", i.e. regulated by the user via self-monitored glucose, but progress has been made towards completely automated "closed loop" systems with feed-back control.
Insulin pump therapy is a means of providing intensive insulin therapy by the continuous infusion of soluble insulin into subcutaneous tissue, hence its alternative description as continuous subcutaneous insulin infusion (CSII).
Insulin pumps were first introduced in the late 1970s using bulky infusers based on conventional syringe driver technology. Now modern pumps are similar in size to a mobile phone, and combine an insulin reservoir and a pumping mechanism. Whilst insulin delivery is described as continuous, in reality the pump infuses a small bolus every few minutes to provide the cumulative
Fig 1a: The Omnipod Patch Pump
Fig 1b: Roche, Animas and Medtronic Insulin pumps hourly dose.
There are two designs for the infusion system: patch pumps are applied directly to the skin with a small length of plastic tubing going directly from the base of the pump into the subcutaneous tissue (figure 1a); whilst the majority of pumps are tethered, the pump being portable and connected to an infusion set with a length of tubing attached to a plastic or metal cannula placed in the subcutaneous tissue (figure 1b).
The infusion set is usually sited on the abdominal wall, but alternative sites include the flanks, thighs and top of the buttocks, and patch pumps can be applied to the upper arms. Patch pumps and certain tethered pumps can be controlled by a separate handset, and there are combined insulin pump and continuous glucose monitoring systems which provide sensor-augmented pump therapy.
Advantages of Pump Therapy
The principal advantage of insulin pump therapy over multiple daily injections is the ability to deliver a variable basal rate, rather than relying on one or two injections of basal insulin each day. Once basal insulin has been injected there is no means of altering its absorption from the subcutaneous depot, so that there may be times when the individual has too much circulating insulin in order to ensure adequate levels at other times. This is particularly true overnight.
Furthermore the absorption of isophane insulins potentially varies significantly from day to day; and whilst analogue basal insulins, such as glargine and detemir, are more reliably absorbed, basal insulin delivery via an insulin pump, is predictable, reliable and responsive to changes in the basal infusion rate, as a result of the small depot of rapid acting insulin present at any one time. Not only
Fig 2: A Diasend Upload showing two different pre-programmed basal rate profiles can the pump user programme different patterns of basal insulin infusion to reflect different situations, such as changes in work shifts or increased insulin requirements pre-menstrually (figure 2), but they can also temporarily decrease or increase the basal rate to respond to a predicted or actual change in insulin need, such as exercise or illness.
Modes of insulin delivery
A variable basal rate has been a longstanding feature of insulin pump therapy, but in recent years there have been developments in bolus insulin delivery. It has always been easier for pump users to deliver several boluses a day, as they do not have to give an injection each time - unlike the individual using multiple daily injections - so they are more likely to give bolus doses for small carbohydrate snacks, to correct hyperglycaemia and even to give divided bolus doses for particularly long or large meals.
Fig 3: A Diasend Upload showing a number of different aspects of insulin delivery, including a conventional bolus, a combination (dual-wave) bolus and temporary basal rate adjustmentModern pumps also allow the user to choose different bolus dose profiles (figure 3): as well as a conventional bolus, a square wave or extended bolus can be delivered with the bolus given constantly over a specified period of time; or the two can be combined as a dual-wave bolus with the user selecting a percentage to be given in a conventional fashion, and the remainder delivered as the extended bolus.
The dual-wave bolus can be particularly useful for dealing with the prolonged blood glucose excursions, often lasting up to 6 hours, seen after high fat, high carbohydrate meals, as is particularly the case with Indian and Chinese foods, pizza and pasta dishes. The pumps now have software included which provides an estimate of the likely circulating insulin levels at any time, so that this can be taken into account when deciding on the insulin bolus dose required, either with food or as a correction. The predicted insulin levels are variously described as active insulin or insulin on-board, whilst some programmes use a predicted glucose level as a measure of the potential insulin deficit or excess. These parameters are used in integrated bolus calculators which give the user advice about what bolus dose to administer.
There is good evidence that pump users who regularly use the more advanced pump features such as temporary basal rates and bolus calculators obtain better glycaemic control. Provision of training on the principles of pump therapy and how to use a specific pump is a vital element of any diabetes service initiating insulin pump therapy, whilst ongoing education is important to reinforce use of advanced pump features and refresh the user’s knowledge base. Insulin pump therapy has been shown to be superior to multiple daily injection therapy in adults and children with type 1 diabetes in terms of optimising blood glucose control, being associated with a lower HbA1c with a reduced risk of hypoglycaemia. The flexibility of insulin pump therapy has also been shown to deliver some improvements in quality of life. There is some evidence that for those on insulin pump therapy progression to sensor-augmented pump therapy can provide a modest additional HbA1c improvement if continuous glucose monitoring is used most of the time.
The evidence base
Insulin pump therapy may also provide benefits for other groups but the evidence base for these is not established, leading the National Institute for Clinical Excellence (NICE) to advise that, in England and Wales, insulin pump therapy is indicated for adults and children 12 years and older with type 1 diabetes and experiencing disabling hypoglycaemia or unable to achieve an HbA1c less than 8.5% (69 mmol/mol); or in younger children as a first-line option for intensive insulin therapy.
NICE specifically indicate that insulin pump therapy is not recommended for type 2 diabetes. However there are individuals with type 2 diabetes who undoubtedly benefit from pump therapy, particularly those who are severely insulin resistant. Similarly there are individuals with type 1 diabetes who would perhaps not meet NICE criteria for pump therapy but in whom there is anecdotal evidence for potential benefit. These include pregnancy; autonomic neuropathy, particularly gastroparesis; painful peripheral neuropathy; extreme insulin sensitivity; and needle phobia.
There are disadvantages to insulin pump therapy, although in experienced centres pump dropout rates are low. Some people find having to constantly wear the pump intrusive, although for some this problem is less of an issue when using a patch pump. Previous concerns about increased risks of ketoacidosis and hypoglycaemia amongst pump users have been disproved by large randomised controlled trials and cohort studies. Infusion site problems, including site infection, may occur, but regular infusion set changes and good hygiene practices minimise the risk.
It is likely that usage of pump therapy will continue to increase, particularly with further technological advances towards closed loop systems which will make it easier for the pump user to maintain glucose levels within target range.
^ Chase HP et al. Post-prandial glucose excursions following four methods of bolus insulin administration in subjects with Type 1 diabetes. Diabetic Med 2002;19:317-321.
^ Wilkinson J, McFann K, Chase HP. Factors affecting improved glycaemic control in youth using insulin pumps. Diabetic Med 2010;27:1174-1177.
^ Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in type 1 diabetes: meta-analysis of multiple daily insulin injections versus continuous subcutaneous insulin infusion. Diabetic Med 2008;25:765-774.
^ Battelino T et al. for the SWTICH study group. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia 2012;55:3155-3162.
^ National Institute for Health and Clinical Excellence. Continuous Subcutaneous Insulin Infusion for the Treatment of Diabetes Mellitus. Technology Appraisal Guidance 151 (Review of Technology Appraisal Guidance 57). London, England: NICE, 2008. http://guidance.nice.org.uk/TA151/Guidance/pdf/English