Management & Treatments
Interventions for Congenital Hyperinsulinism
Medical Treatment - How is Hyperinsulinism treated ?
The aim is to keep the child’s blood glucose level stable (3.5 – 10mmol/litre). Initially, children are managed with high concentration of intravenous glucose containing fluids. Sometimes, glucagon infusion (a medicine used to release stored glucose in the body) might be needed.
Subsequently children are established on feeds and started on the first line medications (diazoxide and chlorothiazide). A heart scan (echo) will usually be done before starting diazoxide to rule out any underlying heart defect. Diazoxide is an oral medication (given 3 times daily) that will aim to suppress the insulin secretion. The side effects include fluid retention and hence, it is always used with chlorothiazide (given 2 times daily), which is a diuretic (a medicine that induces water loss).
In the long run, diazoxide can lead to excessive hair growth. This hair growth resolves several months after diazoxide therapy is stopped. Once children show a response to diazoxide, the intravenous fluids and glucagon infusion will be gradually weaned off
Alder Hey Patient Information Leaflet (Feb 2022 V4)
Diazoxide – First line treatment
- Activates the potassium channel
- Known to be unresponsive in some genetic mutations
- Branded Proglycem or E5 pharma is preferable
- Side effects: please ask your HI Specialist team to explain the side effects.
What happens if Diazoxide is ineffective?
In children, who do not respond to the first line medication, further investigations (genetic tests and
or DOPA PET scan) will be needed to identify diffuse versus focal disease. In diffuse patients,
octreotide, a medication which is given as 6 hourly injections can be tried. Diffuse patients who do
not respond to medical therapy are likely to need surgery to remove the majority of the pancreas.
Children with focal CHI will undergo surgical removal of the focal lesion.
Other treatments that may be considered – please discuss side effects and concerns with your HI specialist team.
- Octreotide
- Lanreotide
- Sandostatin LAR
Future Treatments
GLP-1 antagonists:
- Exendin-9-39
- Glucagon (Dasiglucagon, HM15136)
- Insulin receptor antagonists RZ358
- Pharmacological trafficking chaperones
- Somatostatin analogues -New formulations
The Children’s Hyperinsulinism Charity UK and Ireland is grateful to Clare Gilbert, Clinical Nurse Specialist Hyperinsulinism and Sophie Alexander, Clinical Nurse Specialist Hyperinsulinism for the above information, as part of their ‘Journey of Hyperinsulinism presentation’ at our Family Conference.
Subscribe to our YouTube channel, to see the video presentation coming soon!
Surgical Treatment
Surgery is considered secondary to medical treatment and is often reserved for children for whom drug treatment has been ineffective. Surgery is usually an option for children with focal disease who have identified areas of the pancreas with defective beta cells (usually following a PET scan) and can often offer a cure for CHI. More extensive surgery to remove all or most of the pancreas is only considered an option for those with diffuse disease when medical intervention has failed – but it should be noted that this carries an increased risk of longer-term effects such as diabetes or pancreatic insufficiency, and is not usually seen as curative.
See our webpage on pancreas/insulin for more details: https://hyperinsulinism.co.uk/the-pancreas-insulin/
Measuring Blood Glucose - Why is it important to maintain normal blood glucose ?
A blood glucose level less than 3.5mmol/l is considered as hypoglycaemia in babies and children with CHI. Babies with CHI are constantly reliant on a normal circulating blood glucose concentration for normal function of the nerves and brain, hence the importance of maintaining blood glucose level above 3.5mmol/litre.
CHI is particularly damaging because apart from hypoglycaemia, the insulin suppresses the release of alternative fuels called ketones. Hence the brain is deprived of both glucose and ketones. Once the brain cells are deprived of these important fuels, they cannot make the energy they need to work and may result in seizures and coma. It is this cell damage which can manifest as a permanent seizure disorder, learning disabilities, cerebral palsy or blindness in the long run.
Alder Hey Patient Information Leaflet (Feb 2022 v4)
There are lots of different ways to measure blood glucose on the market and this is just a guide to a few pieces of technology that we have in the UK – It is not intended as a recommendation, nor to be exhaustive.
Glucometers
There are many different blood glucose (BG) meters on the market.
Sometimes it can be a little trial and error to get the right machine for you, CHI families often have their own personal favourite. If you are having difficulties with your meter you can ask your HI Specialist team or GP for advice on how to obtain a new one. Make sure your GP changes the repeat prescription to the new test strips.
Continuous Glucose Monitors (CGM) and Flash Monitors
Flash glucose monitors and Continuous Glucose Monitors let you check your glucose levels without having to prick your fingers. You insert a small sensor into your body that reads your glucose levels so you can see the information on your mobile, or other device. You can set alarms to sound if blood sugars start to go out of range, and to alert to hypoglycaemia.
One of the main benefits of a flash glucose monitor and CGM is being able to review blood sugar levels and understand trends and patterns. This can help you to change routines, or take preventative action e.g if you have identified a particular activity, exercise or time of day is causing your blood sugar levels to drop. They also allow you to see what blood sugar levels are doing at times that you wouldn’t normally be testing. Other advantages may be a reduction in finger prick testing, more independence for older children in managing their condition, more freedom to take part in social activities and school trips, and the ability to share data with your Hyperinsulinism Team.
However there are disadvantages CGMs are not as accurate as finger prick testing and in Hyperinsulinism they are shown to be less accurate. Caution should therefore be applied in ensuring finger prick testing happens at any time of concern, such as if there are signs or symptoms of hypoglycaemia, if the CGM reading seems inaccurate, in times of illness and as advised by your Hyperinsulinism Team. Therefore, if you have a CGM always ensure that you still have and keep on repeat prescription your blood glucose testing monitor, lancets and strips. Some families can find the CGM and flash monitors cause irritation to their child’s skin and it can take some time to get used to the technology.
Why are CGMs and Flash monitors not as effective as finger prick testing?
Flash glucose monitors and CGMs, measure the amount of sugar in the fluid surrounding your cells. This is called interstitial fluid. It’s not quite as accurate as a finger prick test as it lags behind blood sugar levels by up to 15 minutes.
CGM accuracy in Hyperinsulinism is being monitored by the Hyperinsulinism Teams and a recent evaluation of the Dexcom G7 by the Manchester Team can be found here: https://journals.sagepub.com/doi/abs/10.1177/19322968241245923
CGM (Continuous Glucose Monitor) v Flash Monitor.
These are small devices worn just below the skin that measure glucose continually throughout the day and night. CGM devices alert you to hypoglycaemic episodes via the receiver, whilst Flash monitors require you to scan your device over the sensor for measurement.
They are very easy to insert, and basically do the same thing: They test the fluid roughly every 5 minutes and either wirelessly transmit the readings to a handheld monitor, or store the readings to be transferred on demand.
The units and their associated monitors are small and light, and often interchangeable with your mobile phone.
Some devices allow you to remotely monitor the device when connected to a phone – Useful for example if you need to monitor the BGM readings of your children whilst they are at school. As these go beyond a single point-in-time reading obtained from the traditional BG monitor, they are capable of informing and predicting events and can be very useful for gaining better insight into the impact of food, rest, or activity for example.
They have trend arrows, alarms, and alerts informing the user they are dropping or rising at a certain rate or have reached a hypo level.
Insulin pumps are also available both with and without integrated CGM.
