David Levy, MD, FRCP
Insulin Pump Treatment (CSII)
First used at the end of the 1970s, insulin pump therapy is standard treatment for type 1 diabetes, although use varies between countries (e.g. about 1–2% in the UK, probably more now; about 25% in USA, up to 40% in Norway). Only rapid-acting analogue insulin is used, given at a variable low background basal rate, supplemented with mealtime boluses. The technique is used in specialist centres with great success in children and adolescents, and some centres routinely start CSII immediately after diagnosis. In meta-analysis, HbA1c is consistently about 0.3–0.6% lower with CSII than MDI ….
Indications for CSII (NICE 2008)
The National Institute for Health and Clinical Excellence (NICE) has issued broad guidelines for insulin pump treatment, e.g. disabling hypoglycemia despite optimized MDI treatment, HbA1c 8.5% (69 mmol/mol) or more despite high level of care in type 1 patients over 12 years old. Other clinical indications might include:
- hypoglycemia unawareness;
- wide glycemic fluctuations regardless of HbA1c;
- ketosis-prone individuals;
- improvements in HbA1c pre-conception, during pregnancy and where there are potentially reversible microvascular complication (e.g. background retinopathy, microalbuminuria);
- difficulty in managing nocturnal glycemia (hypoglycemia, hyperglycemia, dawn phenomenon);
- irregular shift-work patterns, frequent long-haul travelling;
- intensive exercise (e.g. competitive athletes);
- people requiring either very large or very small doses of insulin.
High levels of motivation and compliance are usually considered necessary, but motivation may improve with treatment, and CSII should be available for a trial period for any patient who is interested and appreciates that the technique, though sophisticated, is not yet a fully automated insulin delivery system.
Advances in pump technology have accelerated recently. They are now very subtly programmable to deliver multiple basal rates at different times of the day and especially night, for example to counteract the dawn phenomenon. Basal rates can be changed temporarily, during periods of inactivity, sports and exercise, menstrual cycles and acute intercurrent illness. Different configurations of boluses can be given, for example spike boluses to correct a high glucose level, extended (square wave) boluses for high fat or high protein meals, combination boluses (immediately followed by an extended bolus), or superboluses (some or all of the basal rate for the next 2–3 hours is borrowed in advance and added to the meal plus correction bolus, to reduce hyperglycemia before a high glycemic index meal).
Further refinements are continually being introduced. Software integrated with the pump can calculate and suggest bolus doses, based on estimated carbohydrate intake and prevailing glucose levels (bolus ‘wizard’). Sensor-augmented pumps, using a continuous glucose monitor fitted at a different site to the pump, can relay glucose data to the pump display. In one of the largest pump studies to date (STAR 3), nearly 500 children 7 years or older and adults were randomized to remain on MDI or changed to sensor-augmented pump treatment (MiniMed Paradigm REAL-Time System; Fig. 4.3). In pump-treated patients, HbA1c fell by a mean of 0.5–0.6% from a baseline of 8.3% (67 mmol/mol), maintained over a year, with a similar result seen in children and adults. There was a clear relationship between the frequency of sensor use and fall in HbA1c, with the greatest fall (about –1.2%) seen in those using sensors between 81 and 100% of the time . There was no significant weight gain, and hypoglycemia was no more frequent than in the MDI group. Recently, semi-automated pumps have been introduced that temporarily interrupt basal insulin delivery when glucose levels fall to predetermined levels (e.g. < 4 mmol/L, 72 mg/dL), and the race is on to develop the software to guide the first fully automated closed-loop feedback pump. So far it has been used to safely control glucose levels overnight in children and adults, but the technological hurdle to extend this successfully to daytime use is formidable.
Checklist of Practical Points Whenever There is a Problem with Blood Glucose Control
Before discussing radical changes to insulin regimens, always check the following, especially when there has been recent deterioration in control.
- Adherence. Ensure that all insulin injections are being given, especially in younger people. Lunchtime, and other, doses of an MDI regimen are often omitted; eliciting this information requires sensitive questioning.
- Check insulin. Confirm type and doses of insulin, compatibility of pens and injection needles.
- Mixing technique. In the few patients who self-mix insulin, check technique; confirm uniform mixing of any cloudy insulins.
- Storage. Modern insulin has an effective shelf-life of about 2 years if refrigerated at 2–8°C, but storage in extreme tropical conditions, hot car interiors, freezer compartments, and airplane holds may cause denaturation. Individual manufacturers’ recommendations vary, but insulin can be kept safely at temperatures below 30°C for about 4 weeks.
- Check injection sites. Lipoatrophy, probably an immune complex-mediated inflammatory lesion, is very rare with human and analogue insulins, though a few cases have been described, even with CSII, where a local reaction to the delivery catheters may be responsible. Lipohypertrophy is still common with human insulin, though it may not occur with analogues. Injection into these sites is often less painful, but absorption may be erratic and delayed. Even where there is no lipohypertrophy, absorption from frequently injected sites can be erratic, leading to glycemic instability.
- Ensure rotation of injection sites between thigh, buttock and abdomen (avoiding the immediate periumbilical area). Avoid injecting the upper arm, which may result in intramuscular injection. Absorption is fastest and most consistent from the abdomen, which is the preferred site for injection of mealtime insulin.
- Injection technique. Pinch skin and give the injection approximately perpendicular to the skin surface; 6-mm pen needles are satisfactory for most people, and reduce the risk of non-subcutaneous injections. Leave the needle in the skin for up to 10 seconds after the injection, pull it straight out, and gently press on the injection spot, but do not rub it.
- Home blood glucose monitoring. Intensify temporarily, concentrating on times of day where blood glucose levels are most erratic. A CGM study is likely to be valuable.
- Consider new-onset endocrine disorders, especially Addison’s disease, autoimmune thyroid disease and coeliac disease. A short Synacthen test is simple and can be performed non-fasting at any time of day. Take blood for baseline cortisol, inject Synacthen (tetracosactide) 250 µg, repeat cortisol measurement at 30 min and 1 hour; a peak cortisol level above 550 nmol/L is an adequate adrenal response.