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Diarrhea can be a symptom of many conditions, but it is particularly key in Neuroendocrine Tumour (NET) Syndromes and types, in particular, so called Carcinoid Syndrome but also in those associated with various other NET types such as VIPoma, PPoma, Gastrinoma, Somatostatinoma, Medullary Thyroid Carcinoma.
Secondly, it can be a key consequence (side effect) of the treatment for Neuroendocrine Tumours and Carcinomas, in particular following surgery where various bits of the gastrointestinal tract are excised to remove and/or debulk tumour load.
There are other reasons that might be causing or contributing, including (but not limited to) endocrine problems such as hyperthryoidism, mastocytosis or Addison’s disease (which may be secondary illnesses in those with NETs). It’s also possible that ‘non-sydromic’ issues such as stress and diet are contributing. It could be caused by other things such as Irritable Bowel Syndrome (IBS). Yes, believe it or not, NET Patients can get normal diarrhea causing diseases too!
I want to give a general definition of diarrhea as there are many variants out there. In general, they all tend to agree that diarrhea is having more frequent, loose and watery stools. Three or more stools per day seems to be the generally accepted threshold, although some sites don’t put a figure on it. It’s not pleasant and just about everyone on the planet will suffer it at some point in their life, perhaps with repeated episodes. Normally it’s related to some kind of bug, or something you’ve eaten and will only last a few days before it settles (acute diarrhea). Diarrhea lasting more than a couple of weeks is considered chronic and some people will require medical care to treat it. It can also be caused by anxiety, a food allergy/intolerance or as a side effect of medicine. Pharmacists and GPs will be seeing many patients with this common ailment every single day of business and the cause of diarrhea is hugely more likely to be regular sources than NET related.
Sorting out the symptoms – post diagnosis
I like to describe this as the Neuroendocrine Cancer jigsaw. It’s a really difficult one and sometimes you cannot find a piece, or the pieces won’t fit. However, metaphorically speaking, the missing piece might be a NET specialist presentation, a comment, statement or view from another patient, a link to an article from a reputable source, or even something you do to improve your lot – there might even be trial and error involved. It might even be this blog post!
This disease is so individual and there are many factors involved including the type of syndrome/NET, patient comorbidities and secondary illnesses, consequences of the surgery or treatments performed, side effects of drugs – all of which is intermingled with suspicion and coincidence – it’s that jigsaw again! I always like to look in more detail to understand why certain things might be better than others, I always challenge the ‘status quo’ looking to find a better ‘normal’. I really do think there are different strategies for syndrome induced diarrhea and that which is a result of treatment or a side effect of treatment. There are also different prices, with inhibitors costing thousands, whilst classic anti-diarrhea treatments are just a few pennies. Adjustments to diets are free!
When I was discharged from hospital after the removal of my small intestinal primary, I was in the toilet A LOT (I was actually in the toilet a lot before I was discharged – check out my primary surgery blogs here). My surgeon did say it would take months to get back to ‘normal’ – he was right, and it did eventually settle – although my new ‘toilet normal’ was soft and loose and several times daily. My previously elevated CgA and 5HIAA were eventually back to normal and my flushing had disappeared. I didn’t have too many issues with diarrhea before diagnosis. Deduction: my issues are most likely not syndrome induced.
How do you work out whether diarrhea is caused by a hormone producing tumour or by the side effects of treatments? There’s no easy answer to this as both might be contributing. One crude but logical way is to just accept that if you have normal hormone markers, for example 5HIAA (there could be more for other tumour/syndrome types), and you’re not really experiencing any of the other classic symptoms, then your syndrome might be under control due to your treatment (e.g. debulking surgery and/or somatostatin analogues, or another drug). My Oncologist labels me as ‘non-syndromic’ – something which I agree with. I’m 99.999999% sure my issues are as a result of the treatment I’ve had and am receiving
Diarrhea caused by a Syndrome
When you consider the explanation above, it’s not really surprising that diarrhea related symptoms can delay a diagnosis of Neuroendocrine Cancer (and most likely other cancers too, e.g. pancreatic cancer, bowel cancer). For example, diarrhea is the second most common symptom of Carcinoid Syndrome (Flushing is actually the most common) and is caused mainly by the oversecretion of the hormone Serotonin from the tumours. Please note diarrhea in other types of syndromes or NETs may be caused by other hormones, for example it may also be caused by excess calcitonin in the case of Medullary Thyroid Carcinoma or VIP in the case of a functional pNET known as VIPoma. I’ve heard stories of people being told they have IBS or something similar for years before they received what is now a late diagnosis and at an advanced cancer stage. This is only one of the reasons why NETs are not an easy condition to diagnose, although it is possible that some people actually had IBS (or something similar) and it was masking the NET. Even after treatment to remove or reduce tumours, many people will remain syndromic and need assistance and treatment to combat diarrhea induced by a NET syndrome (see below).
Like many other NET patients, I’m on a 28-day injection of somatostatin analogues (in my case Lanreotide). Both Octreotide and Lanreotide are designed to reduce the effects of NET syndromes and therefore can often make a difference to syndrome induced diarrhea. These drugs also have anti-tumour effect and so even if you are not syndromic or they do not halt or adequately control syndrome induced diarrhea, they are still a valuable contribution to NET treatment.
Some syndromic patients find they still have diarrhea despite somatostatin analogues and they end up having ‘rescue shots’ or pumps for relief (both of these methods tend to be Octreotide based). (Hopefully they are not getting confused between diarrhea caused by the non-syndrome effects – see above). Some have more frequent injections of the long-acting versions of somatostatin analogues which has the effect of increasing the dosage. There’s a new drug available for those whose carcinoid syndrome induced diarrhea is not adequately controlled or perhaps they are unable to have somatostatin analogues as a treatment. Telotristat Ethyl works by inhibiting tryptophan hydroxylase (TPH), a chemical reactor involved in the manufacture of serotonin, which is the main cause of syndrome induced diarrhea. It was approved by the US FDA in February 2017, EU areas in September 2017, and is on the way to being approved elsewhere. Read about this drug here.
Diarrhea as a Consequence (Side effect) of Treatment for Neuroendocrine Cancer and Other Conditions
(i.e. not caused by a syndrome)
All cancer treatments can have consequences and Neuroendocrine Cancer is definitely no exception here. For example, if they chop out several feet of small intestine, a chunk of your large intestine, chunks (or all) of your stomach or your pancreas, your gallbladder and bits of your liver, this is going to have an effect on the efficiency of your ‘waste disposal system’. One effect is that it will now work faster! Another is that the less effective ‘plumbing’ may not be as efficient as it was before. There are also knock-on effects that may create additional issues with the digestive system including but not limited to; Malabsorption and SIBO. The latter is evolving scientific evidence. I recommend you read my posts on Malabsorption and SIBO.
Surgery can often be the root cause of diarrhea. This is particularly involving terminal ileum resection in cases of midgut primary surgery but can also be attributed in part to the removal of the gallbladder. One of the causes can be Bile Acid Diarrhea. See the special “jigsaw piece” section below or click here.
Surgery of the pancreas can also produce effects such as exocrine pancreatic insufficiency which can lead to a malabsorption condition known as steatorrhea which may be confused with diarrhea (although some texts call it a type of diarrhea). It isn’t really diarrhea, but it may look like it given the presentation of the faeces and patients may suffer both diarrhea and steatorrhea concurrently. Patients will recognise it in their stools which may be floating, foul-smelling, greasy (oily) and frothy looking. Treatment options will mainly include the use of Pancreatic Enzyme Replacement Therapy or PERT for short (Creon, Nutrizym, etc).
Many non-surgical treatments can also cause diarrhea, including but not limited to; somatostatin analogues (see below), chemotherapy, biological targeted therapy (e.g. Everolimus, Sunitinib), radiotherapy.
Somatostatin analogues are an interesting one as they are designed to inhibit secretion of particular hormones and peptides by binding to the receptors found on Neuroendocrine tumour cells. This has the knock-on effect of inhibiting digestive/pancreatic enzymes which are necessary to break down the fat in our foods leading to Malabsorption of important nutrients. This may worsen the steatorrhea in pancreatic NET patients but also lead to steatorrhea in others with non-pancreatic locations who have been prescribed these drugs.
Other conditions may actually be the cause of diarrhea or the treatment for those conditions. For example, it is possible that people actually do have Irritable Bowel Syndrome (IBS) in addition to NET (often misdiagnosis cases are because IBS is masking the NET). Treatment therapy for common conditions may also be contributing, for example, the use of Proton Pump Inhibitors for acid reflux.
I read that many people find basic ‘Loperamide’ (Imodium) helps, and I tend to agree with that if you are non-syndromic and just need that little bit of help. I decided a long time ago I would not become ‘hooked’ and only really take it for two purposes: 1) if I have a bad patch and 2) if I’m going on a long journey (i.e. on a plane perhaps). I estimate I’ve used 4 packets in as many years. Loperamide decreases the activity which causes intestinal motility (peristalsis). This has the effect of increasing the time material stays in the intestine, therefore, allowing more water to be absorbed from the fecal matter. Ideal for those with a shorter bowel due to surgery and advice from a medical professional is always advisable.
To reduce the risk of malabsorption-induced diarrhea and steatorrhea, both of which can lead to loss of valuable nutrients, the use of Pancreatic Enzyme Replacement Therapy (PERT) might need to be introduced as required by your NET specialist.
Primary lactose intolerance is not directly related to NET, but another potential cause of diarrhea can be related to secondary lactose intolerance from small intestine surgery or as a side effect of chemotherapy or radiotherapy – read more here or click on the picture below.
Fructose intolerance is not directly related to NET, but another potential cause of diarrhea can be related to dietary fructose intolerance from small intestine surgery or other damage to the small intestine (in addition to the normal causes – read more here or click on the picture below.
As you can see from above, the differential diagnosis of non-syndromic diarrhea in a NET patient is potentially an extensive list of possibilities but I wanted to focus this section on the area of bile system impairment which leads to a form of malabsorption causing diarrhea. This is an under-reported or at least an under-discussed problem within the community. So, I guess I’m focusing on tumours where there has been some sort of bowel resection and/or gallbladder removal (although other resections may be involved or contributing). I remember one question in a patient group along these lines “surgery and somatostatin analogues have not improved my carcinoid syndrome; I still have diarrhea” ……. cue a long and difficult explanation. They’re difficult because of two things, firstly it’s a complex scenario, and secondly because it isn’t an exact science. But I’ll try to at least give you some food for thought if you think this might apply to you. At the very least I hope to give you some tools in order to have a fairly sensible conversation with your doctors and nurses (and dietitians where applicable). Before progressing, I wanted to emphasise this is not the same type of malabsorption caused by exocrine pancreatic insufficiency (EPI) which can potentially lead to something known as steatorrhea (amongst other things). Read about Bile Acid Malabsorption and Bile Acid Diarrhea here or click on the picture.
Clearly, I cannot offer any professional medical advice on coping with diarrhea, I can only discuss my own situation and what I found worked for me. Don’t forget, like many diseases, what works for one, might not work for another. However, I did tackle my problems following the advice of an experienced dietitian who specialises in NETs. That said, I was ‘sleep walking’ for over 2 years thinking my issues were just part of the way things were after my treatment. I was wrong about that!
As for my own strategy, here’s things that helped me:
- made some changes to diet (they were not huge changes),
- included supplementation where necessary,
- reduced stress as far as is practical to do,
- maintained a diary to help with monitoring progress or setbacks,
- hydration is also important (….still working on that one),
- started taking PERT (Creon) on 23 Dec 2017 (changed to Nutrizym Feb 2019) but looks reasonably positive so far.
With no fancy and expensive drugs, I’ve gone from 6-8 visits to 1-2 visits (as a daily average, it’s actually 1.5). This didn’t happen overnight though; it took a lot of time and patience. All of this doesn’t mean to say I don’t have issues from time to time …… because I do!
I think it’s really important that people be sure what is actually causing their diarrhea after diagnosis so that the right advice and the optimum treatment can be given. Sometimes it’s really difficult for healthcare professionals to pin this down and some experimentation is required. Always check with your healthcare professional before taking any medication/supplement. However, I still struggle sometimes with the ‘quality’ of stool, and I guess that is possibly a combination of malabsorption plus diet choices.
Listen to Dr Wolin talking about this particular jigsaw puzzle – click here
Also see a nice article that came out of NANETS 2017 – click here
But this recent article is first class – so if you’re not happy with my patient-derived view, listen to NET experts. Click here.
Of course, some people sometimes have the opposite effect but that’s in another blog here – Constipation
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.
Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.
Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
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19 thoughts on “Neuroendocrine Cancer – the diarrhea jigsaw”
[…] Acesso em agosto de 2018. 5. Living with Neuroendocrine Cancer. Disponível em: https://ronnyallan.net/2016/09/15/neuroendocrine-cancer-the-diarrhea-jigsaw/ Acesso em agosto de 2018. 6. Targeted Oncology. Diagnosing and Treating NET-Related Diarrhea. […]
[…] Acesso em agosto de 2018. 5. Living with Neuroendocrine Cancer. Disponível em: https://ronnyallan.net/2016/09/15/neuroendocrine-cancer-the-diarrhea-jigsaw/ Acesso em agosto de 2018. 6. Targeted Oncology. Diagnosing and Treating NET-Related Diarrhea. […]
Hello. I would like to share my story. I will try to make it short.
In 2007 I was diagnosed with carcinoid cancer in my liver. During the surgery they also found primary tumor in my bowl. So they removed big part of my bowl (now I have ileostomy), half of my liver and piece of my pancreas.
During all this time I had 3 more surgeries. They tried different types of treatments. Nothing helped. I still have numerous tumors in my liver and it spread to my bones.
So recently, my doctor recommended lanreotide injections. I started in September 2017. Right away my stool became weird. Very greasy, light yellow. The main problem was the amount. I had to go to washroom every hour to clean my pouch. So, at night I could not get rest.
I went online and I found this blog by Ronny Allan. I talked to my doctors. They prescribed me Viokace 20. It contents 3 different enzymes : Amylase, Lipase and Protease.
Everything changed dramatically. My stool is normal as before, now I can sleep.
I am really grateful to Ronny Allan for your research and sharing. Thank you very much.
glad to hear you’re doing OK and thanks for the kind comments. Good luck with the Pancrelipase treatment
Interesting to read about symptoms relating to post-surgery. I developed asthma and thyroid-inufficiency following removal of pituitary adenoma, and I’ve only had diarrhea/gas probs following intestinal surgery to remove mid-gut carcinoid.
thank you Ronny
Hope you’re doing OK? I get the thyroid side effect following pituitary, never thought about asthma, need to study it
Thanks for your reply Ronny. Think I’ve read somewhere a link re NET/asthma but be good if you also come across any material. Like you I’m on monthly lanreotide since 2014 (mid-gut surgery and diagnosis was 2011). My biggest prob is the gut/toilet + gas thing, particularly bad in the evenings. A very isolating disease.
The Gut/toilet/gas thing is so individual, probably best handled by an experienced NET dietition. However, understanding the source of the issues can be very helpful. Below, i had assumed the asthma was as a result of pituarity ademo removal and that is way beyond my knowledge. Asthma can indeed be a symptom of carcinoid syndrome, particularly foregut/ bronchial NETs. The way I see it is if your hormone marker tests are normal and you’ve had/having treatment, then you need to assess the symptoms as potential treatment side effects. I have worked and worked myself from an average of 5-6 visits to the bathroom down to 1.5 average per day (i.e. pretty normal) and gas is reduced. I havent changed my diet in any radical sense, i just understand why certain things affect me. For example, if you’ve had small intestinal surgery (e.g. right hemicolectomy), you will have a shorter bowel and therefore a speedier system. You need to work on slowing that down. Additionally, you may have other potential problem sources such as bile acid malabsorption and bacterial imbalance or overgrowth. Somatostatin analogues will exacerbate these issues by inhibiting digestive enzymes creating malabsorption issues such as steatorrhea which some people confuse with diarrhea. Again, there are things you can do to reduce this. Add diet to the issue and gas can become a problem. It’s not an exact science. I think all SI NET patients and certain pNETs need to assume they have IBS and work to reduce these effects and not simply assume they have syndromes. Not easy. Have you read my nutrition series of posts?
Ronny , my sister is raising g funds for PLANETS by having a lunch do at 8 Stafford Road Swanage on Friday tomorrow from 1-5 . Can you get there ? Hope to see you there Steph xx
Sorry Steph, I won’t be able to make it. Thanks for thinking of me though 😃
Dear Ronny , interested to read that the lanreotide can help with managing diarrhoea . I actually find the four weekly injections actually give me days of diarrhoea ! Usually kicks in about 24 hours after the injection . I get the same old steatorrhoea type faeces . This means I’m going to the loo upwards of 15-17 times a day !! I’m now looking at a low histamine diet as I reacted badly to aubergine and my son asked me if I had looked at histamine as a possible cause . My son had a client, he is a personal trainer ,who had pursued this after suffering for years with IBS . She rnddd up in Switzerland and sent me details of screalkh interesting site . histaminintoleranz.ch . The site gives a full list not only if food but also of drugs . I fog X this really useful as both codeine and ibuprofen were giving me diarrhoea of epic proportions ! I then discovered a really good app. This allows me to look at most foods and through a traffic light system lets me know quickly the foods histamine levels .. German gebhardt. Might be worth a look . On answering feed back I was told ibuprofen was a very good histamine inhibitor but it’s important to get pure ibuprofen as the additives used to make tyectsblets can affect anyone with histamine issues . This is all he’s fif me but really does appear to help with my diarrhoea . Very interestingly watercress and pea shoots are a reall goid natural histamine inhibitor so I try to have those at every meal . Ok I’m still at above ten levels a day if going to the loo but if I’m strict about following the diet I do have some relief . I met you Ronny at the Southampton PLANETS meeting back in July . Be good to meet up again at the next ? Steph xx
Steph, everyone is so different! I have heard of people getting worsening diarreah after Lanreotide, for some it’s a short term issue. I personally find it odd as the drug should show things down! The drug inhibits digestive enzymes this why you see some steatorrhea. The steatorrhea can be caused by surgery (which can cause a decrease in digestive enzymes) and the Lanreotide can make it worse due to its inhibiting function. It also inhibits other stuff which is good but we need to manage certain side effects. Now ….. I don’t class steatorrhea as diarreah which is an effect rather part of the digestive process. Steatorrhea only effects me after a eating certain things plus I tend to see a worsening 24 hours after Lanreotide but it’s short lasting, perhaps 1 or 2 days,
Have you been tested for histamine? I’ve read that foregut tumours release more histamine than midgut. Personally I would be concerned at taking long term ibuprofen. It does sound like you need NET dietician specialist advice from someone like Tara Whyand. Why don’t you give Mark Southern a call? (He’s our specialist Nurse based in Poole).
Hi again Ronny , interesting read but fur me I get even worse diarrhoea the first ten days of Lancreotide injection . A chance comment has led me to low histamine diet . That’s seems definitely part of the problem and hopefully the solution . Not than its getting better .. It’s just when I follow low histamine diet I don’t get the ’20 odd goes to the loo days’ .. More about 11 times . Why does this always start at 4 in the morning though ?
I’m about to have a liver biopsy, in two days time, to see how aggressive the tumours are in my liver with the thoughts of doing chemo after those results are in . For me it’s the diarrhoea that causes the most disruption to my life not the cancer !! I’m totally convinced ( most days) that the cancer can be sorted but the diarrhoea is overwhelming . I daren’t eat at night . Just have a good breakfast .. Porridge made with almond milk and then low histamine lunch . Might have a small snack .. two white pieces of toast( seem to be able to tolerate that amount of bread ) with two egg yolks for very early supper . Getting to grips with all this is difficult as I am allergic to Immodium AND Codiene ( Codiene high histamine ) so actually gives me diarrhoea . Any tips ? I’m reading about DAO. Is that something you’ve looked at ? At present I’m in thyroxine fur low thyroid .. Creon whenever I eat .. Ipramazole once in morning . Today I’m picking up VSL#3 . Think that’s once or twice a day .
It’s a very difficult jigsaw! Read about Telotristat Ethyl, due in service next year. https://ronnyallan.com/2016/03/31/telotristat-ethyl-an-oral-treatment-for-carcinoid-syndrome/
Here is my top tips that worked for me:
1. Reduce stress where possible
2, make sure you’re not deficient key nutrients, in particular ADEK and B12
4. Keep a diary, see if you can identify triggers. Cut or reduce these triggers. Some balance is required on fibre (especially after surgery – small intestine NETs)
5. Consider probiotics to help balance bacteria (more important after surgery)
Always a delicate subject Ronny, but glad you have put it out there as it can be such a big part of this illness, and have massive impact on QoL. Creon has been a major help for me too.
Yes, been ‘umming and ahhing’ about this one, very variable and complicated. And of course, you can get 1000 variations of the theme on forums. Lost count of people saying they still have “Carcinoid Syndrome” immediately after intestinal surgery……..erm. I did cover PERT in my malabsorption blog which I feel it’s more related to. Steatorrhea isn’t really diarrhoea but there is clearly an overlap and possible to have both simultaneously.
I think by encouraging conversation people will be more comfortable discussing, and in turn better understand what is syndrome and what isn’t. I suppose some of it comes down to that stiff upper lip you talked about😉
I have no problem discussing it, mind you I was brought up in a family full of nurses (didn’t inherit the gene though!!).
I found this post interesting for a number of reasons — I’m a relatively recently diagnosed NET patient (small intestine) and one reason everybody thought I had inflammatory bowel disease for over a year was that a first-degree relative DOES have inflammatory bowel disease (which, for the record, is not IBS and is clinically much more serious). I was not at all surprised that the doctors were misled because, knowing my own relative’s symptoms, I had *almost* all the same ones.
But anyway — inflammatory bowel disease (IBD) patients also learn very fast to communicate about topics, and use words, that healthy people might find off-color. If a person living with epilepsy can refer casually to a seizure, and a person living with diabetes can speak casually of their ‘levels’, why should we not be able to refer to our own clinical histories to explain what is going on? Many commonalities here and in both cases education of those healthy people is part of our Grand Challenge. Keep up the good work, Mr Allan.
Great comment, thanks. I hope you’re doing OK