Wednesday, 23 October 2013

What I've been reading

Image of the book cover

A Handful of Dust
by Evelyn Waugh

narrated by Andrew Sachs
"After seven years of marriage, the beautiful Lady Brenda Last is bored with life at Hetton Abbey, the Gothic mansion that is the pride and joy of her husband, Tony. She drifts into an affair with the shallow socialite John Beaver and forsakes Tony for the Belgravia set."
Evelyn Waugh can write such dry comedy that it came as a surprise to find this book not funny at all. A sad story of a marriage breakdown, tragic death and imprisonment, and most characters so self-obsessed and selfish. Most of the time I was listening I didn't think I liked it, but he is such a good writer and Sachs such a good narrator that, despite everything, I would class this as a good book. I wouldn't suggest anyone read it for laughs, though.

Image of the book cover

The Call of the Wild
by Jack London

narrated by B. J. Harrison
"Buck is stolen away from his comfortable life as a pet in California and sold to dog traders. Surrounded by cruelty, Buck’s natural instincts and behaviour begin to emerge as he works as a mail carrying sled dog, scavenging for food, protecting himself against other dogs and sleeping out in the cold snow."
This is a splendid book, shorter than I remember, but perfect for the car journey. Nothing more to say!

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Type 1 Diabetes in Children, Adolescents, and Young Adults: How to Become an Expert on Your Own Diabetes
by Ragnar Hanas
"This practical, easy-to-read book tells you everything you need to know to take good care of your diabetes. Its strengths lie in its ability to connect with the reader, to explain and to make the reader understand medical knowledge in a clear and concise manner."
This enormous book has taken me a full nine months to read, and as I reached the last pages I knew that if I were to start at the beginning again, I would get just as much out of it as the first time through. I will do that at some point, but after nine months of hard slog I think I will give it a break and do more leisure reading until the New Year.

Image of the book cover

Less Than Angels
by Barbara Pym

narrated by Patience Tomlinson
"Less Than Angels follows the loves, works and hopes of a group of young anthropologists. Catherine Oliphant is a writer and lives with handsome anthropologist Tom Mallow. Their relationship runs into trouble when he begins a romance with student Deirdre Swann, so Catherine turns her attention to the reclusive anthropologist Alaric Lydgate, who has a fondness for wearing African masks."
Anthropology is an acquired taste, I imagine. This is a gentle story, sauntering through the narrative with hardly any sense of forward motion, so that I became quite impatient for something to happen. With patience, though, I came to recognise the characters and their personalities, and realised I was reading a book that required no effort and presented no challenge. Which is fine, once in a while.

Saturday, 19 October 2013

Hypoglycaemia treatments

Hypoglycaemia, or a 'hypo', happens when the level of glucose in the blood falls too low. It is not caused by diabetes, because the effect of diabetes is the opposite: high blood glucose levels, or hyperglycaemia. Hypos in people with diabetes are caused by the treatment of hyperglycaemia, not by the diabetes itself.

Very few people who are not diabetic will ever experience hypoglycaemia, because the systems that manage glucose homeostasis are very sensitive to blood glucose level, and keep the concentration very steady between about 4 and 7 mmol/L. But in diabetes, these systems are pretty much messed up along with the pancreatic beta cells. Not only is the insulin response defective, but responses to other hormones that regulate glucose can be blunted too.

In someone with a fully functioning pancreas, receptors in the beta cells of the pancreas islets respond to rising levels of blood glucose with a corresponding and synchronous release of insulin. This facilitates the transport of glucose out of the bloodstream and into cells around the body for use in generation of energy, or into storage in the form of glycogen or fat. As the level of blood glucose falls, the secretion of insulin tails off but a different hormone, glucagon, is released from alpha cells in the same islets. Glucagon stimulates the secretion of glucose into the blood by the liver, either from stores or by the creation of new glucose from scratch.

In someone with diabetes, the matching of blood glucose and insulin is no longer finely tuned and synchronous, but rough and ready and very much asynchronous. When the blood glucose level falls too far or too fast, the level of insulin cannot be unconsciously adjusted down because it is coming from subcutaneous fat depots or an insulin pump rather than the minutely adjustable pancreatic beta cells. Due to the presence of insulin, the glucagon response is not as effective as it should be, and glucose may continue to be removed from the circulation rather than pumped into it.

This is a gross simplification of the many complex hormonal pathways involved in glucose metabolism, but it will do. People with diabetes who inject insulin or use medications that stimulate the pancreas to secrete insulin can't turn their insulin off automatically when they don't need it any more, and are therefore at risk of hypoglycaemia.

Most systems in the body can use glucose or fatty acids to supply their energy, but the brain depends on glucose, although it can utilise ketone bodies (a by-product of fat metabolism) if necessary. When blood glucose concentration falls, the brain signals its displeasure by provoking the nervous system to put out a series of escalating warnings, culminating in stress hormones such as adrenaline and cortisol, in order to generate a flood of glucose to fuel 'fight or flight'. This is what is responsible for the hypo warning signals such as sweating, tingling of the lips or extremities, irritability, dizziness or unsteadiness, which help a person with diabetes to realise that blood glucose is dropping. Hypo unawareness, which I referred to in the post about islet transplantation, is so dangerous because the diabetic person is unable to detect low blood sugar until it is too late.

If untreated, hypoglycaemia can lead to impairment of cerebral function (confusion, drowsiness, inattention), convulsions and unconsciousness. In most cases the glucagon response kicks in and the liver eventually secretes a load of glucose into the blood. A hypo is not pleasant to experience, and there is always an underlying fear of more serious consequences.

The generally accepted definition of a hypo is a blood glucose level less than 4 mmol/L ('Make 4 the floor'), and if this happens, then treatment is advised. If the person is using an insulin pump, then it also makes sense to suspend insulin delivery until blood glucose has stabilised.

First line treatment is to eat or drink something that contains 10-20g of fast-acting carbohydrate, ideally in the form of easily accessible glucose. Energy drinks such as Lucozade are very handy, as are sweets such as jelly babies, fruit pastilles, jelly beans, wine gums or Haribo - these all contain glucose or glucose syrup in their ingredients. Sucrose takes a little longer to be broken down and converted into glucose, but sugary fizzy drinks such as cola still work. There is some argument about whether fruit juice is suitable as a first-line treatment because its sugar is in the form of fructose, which has a longer metabolic pathway than sucrose, but real-life trials suggest that it works just fine. There are also dextrose tablets that are designed to provide fast-acting glucose, but these are fairly unappetising, which can be a good thing - you may fancy a quick snack of jelly beans, but you are unlikely to eat dextrose tablets for fun.

The quantity of carbohydrate is important, because too much will send blood glucose too high, potentially leading to a need for correction downwards and a roller-coaster ride for the next few hours, or even days. The aim is to raise the blood glucose level back above 4 mmol/L very quickly, but ideally not above 7 or 8 mmol/L. To find out if this is the case, the second stage of hypo treatment is to wait about 15 minutes and test again. If the blood glucose level is still below 4 then it's a good idea to repeat the dose of fast-acting carbohydrate, wait another 15 minutes, test again, and repeat a third time if necessary. If blood glucose is still too low after three attempts, it's time to call the paramedics.

In most cases, one treatment will be enough to bring blood glucose back up again. At this point, the game is not over, because whatever caused the hypo in the first place may still be present, so the second line treatment is to eat or drink something that contains 10-20g of medium- or long-acting carbohydrate. If it's a mealtime then the meal would do, but otherwise it could be a starchy snack such as toast, biscuits, crisps, chocolate, fruit, popcorn or yogurt. Milk falls into this category because lactose follows an even longer pathway than fructose or sucrose before being converted to glucose.

The above paragraphs presuppose that the individual is conscious and alert enough to eat or drink. If the person is conscious but not alert and there is someone to assist, there are glucose gels that can be squirted into the mouth as first-line treatment. If the individual is not conscious then nothing should ever be put into the mouth - time to call the paramedics.

There is one other self-help option: an injection of glucagon, which can be administered by a partner or family member who has been shown how to do it. It is not as straightforward as, say, an insulin injection, because glucagon is not stable in solution so has to be prepared by mixing two components on the spot - not easy to manage when your loved one is unconscious or convulsing. But you should have called the paramedics before starting on the path to the glucagon injection, so they should be there to help very soon.

Part of the support and information we give to people with diabetes is how to deal with hypos. We may cover the many and varied reasons why hypos might occur, discuss the law as it applies to diabetes and driving, and I have even given advice about what to do about hypos underwater when scuba diving. But we were especially challenged by one patient with Type 1 Diabetes who does not read, write or speak English.

When I asked colleagues if we had anything that might help, I was sent some fairly crappy illustrations of hypo treatments, and I wanted to do better. 'Crowd-sourcing' using Facebook turned up a photographically oriented friend who volunteered his daughter to help out. I produced a specification for the items and quantities that I wanted photographed, and after some prompting, a terrific set of pictures were the eventual result. I have had them printed and laminated, and plan to use them either with those who need visual rather than written information, or as a teaching aid. I think they're great!

Tuesday, 15 October 2013

Many job opportunities

Two geese swimming in a lake
Munich, March 2013
Following responses to the last blog post, here is a brief update as to my comings and goings: I have acquired a new job, and maybe will get one or two others, and very nearly kept the one I already have.

A permanent Diabetes Dietitian job was advertised much closer to home, the only catch being that it is only 20 hours a week. After much consideration and discussion with family and employers, I applied, with the verbal assurance that my current 35-hour job could probably be tailored to accommodate me if I were to be offered the new job. The interview went well, especially as one of the two interviewers was my previous boss and had seemed very encouraging when I had asked whether she thought I should apply.

I was offered the job, which was very pleasing, and I went back to talk to my current employer about reducing my hours to suit. Oh dear, despite previous assurances, it wasn't quite that simple, because of non-negotiable commitments like the multi-disciplinary ante-natal clinic. If new job needed me on a Wednesday and current job also needed me on a Wednesday, then an irresistible force had met an immovable object and I was caught in the middle. After a bit more thinking, I have gone ahead and accepted the new, closer, permanent but part-time job. We are now negotiating over whether I am who I say I am, and whether I am a criminal. Well, not exactly, but nearly.

In the meantime, another post was advertised, also part-time and about 15 hours and in the same location as I am currently based (i.e. about 60 miles from home). Perfect - except that the advertised date and time for the interview were impossible for me to attend, because I had a clinic with patients booked in and nobody who could cover. Luckily, they have agreed to accommodate me at an alternative time, which they are under no obligation to do, so that interview will be happening this week. It is not quite a regular job because it involves delivering courses which might not be scheduled in the time I have available every week.

The third job is part of a European project which I think I have briefly mentioned before. They are happy to take me on in principle, delivering some of the group weight management sessions, but clearly want to see the outcome of all these other employment options before committing to employing me.

Meanwhile I have been trying to finish the module I'm doing towards an MSc in Advanced Dietetic Practice, and for the first time in my career had to ask for an extension to the deadline because I just can't fit everything in. The pressure of keeping all the plates spinning has also had an effect on my organisational ability, because I have had terrible trouble with all the documentation that I need to prove I am qualified and not a criminal and am actually who I say I am. It has taken two weeks for me to assemble everything in the same place.

And there have had to be trips at weekends, to London for a family do and get-together with friends, to Cambridge for a 30th anniversary dinner, the car needs another few things sorting, I really must revisit my Will which is dangerously out of date, I have played in a badminton match for a team in my weekday home, and the boiler is about to blow up and Mr A and I can't seem to find the time to make the necessary decisions about its replacement. He has had an exam and is about to have a job interview as well.

We often fret about our inefficiencies while appreciating that we are extremely lucky really, and there is nothing truly bad about our situation - as long as we can sort the boiler out before it breaks down for good.

Tuesday, 8 October 2013

Talk to me

Apples with hearts on their skins

My creative juices are waning. I am at low ebb. The tide of my imagination is way, way out to sea, and most evenings I want to retreat into some sort of cushioned cocoon and be warm and dry and quiet until morning, when the alarm drives me out into the cold. I am tormented by my unfinished case study, preying on my mind like a hungry maggot. I have started waxing poetic, and it's not pretty.

I would like to reach out to you, my readers. My blog statistics show that you are few (about 30, I think) and I think I know most of you by name. I need your help, advice, ideas, I want to extract all the goodness from your brains and use it to fuel my ambitions.

What am I talking about? Well, this has been a monologue for too long. In my previous incarnation as Student Lola, people commented. People I didn't know, but came to know, through their thoughts and views. As Dietitian Lola I am less promiscuous, I hardly comment on other peoples' blogs although I read them assiduously. In return, I receive few comments except through email and Facebook. This is OK.

But tonight I am weak, I crave company. I particularly yearn to know who is out there, especially if you have been silent up to now. I am braced for disappointment (like the time nobody came to my leaving party), so I am resilient, I will cope if you all remain silent. But I would very much like to hear from you.

What you can do for me is to tell me stuff. What do you find interesting? What do you like reading about? I'm not promising to fulfil your requests, oh no, if you want to read about the pros and cons of generic MP3 players or whatever happened to Opal Mints, I'm not the one to satisfy you. But if it's bordering on the realm of Lola Life - dietetics, diabetes, living away from home, working in the blasted NHS ('blasted' as in the Shakespearean heath), modest holidays in ordinary parts of the UK - then give me a hook to hang a blog post on and I may be inspired.

Or you could tell me what you like about my blog. Don't bother telling me what you don't like, because it's my blog and I do what I like. Don't be gushing or complimentary - if nobody read a single post I would still be writing them - but feel free to come out of the shadows, 'de-lurk', and shout something across the river running between us. And please, please, even if you don't have a formal online persona, do stick a name on the end - it doesn't have to be your real name, just make something up, it's fine. I am listening.

Wednesday, 2 October 2013

Pancreatic islet research

Lots of little pink flowers
National Botanic Garden of Wales, May 2013
Last week I visited the Islet Research Laboratory (IRL) in Worcester. I was assisted in this endeavour by the local Diabetes UK group, who had arranged a minibus to take a select few on this jolly trip. I have written about this group before, and suffice to say that most of the group did not exhibit behaviour significantly different from what I experience at their meetings. But the quality of the material presented by the researchers made up for any shortcomings of the party.

There are a very few centres in the country where this type of work is done. The islets in question are the Islets of Langerhans, which are the structures within the pancreas that contain insulin-secreting beta cells. The research team extract clumps of islet cells from cadaveric donor pancreata* by dissolving away the tissue around the islets, and then infuse them (sometimes on several occasions) into the hepatic portal vein of the recipient. The islets are transported to the liver and lodge in the tissue there, and somehow a blood supply is created from nowhere (vascularisation) to nourish them and to transport away the insulin that they manage to secrete. The fact that any of this works seems to me to be a miracle, much like throwing mortar and bricks randomly into house foundations might cause a habitable bungalow to emerge.

Although the techniques are still experimental, islet transplantation is approved for patients within the NHS. Recipients are very few (208 worldwide, 34 in the UK), partly because donors are very few, and partly because the selection criteria are so stringent. Most qualify due to severe hypoglycaemia unawareness, which can be utterly debilitating, leading to incapacitating hypoglycaemia with no warning. Others might be suitable recipients because they are already taking lifelong immunosuppressant medication following a kidney transplant.

The success rate of islet transplants is improving, measured by independence from insulin injections, but only 10% of transplant recipients are still insulin-independent after 5 years. It seems, however, that even though they have to return to insulin injections, some recipients recover their awareness of hypoglycaemia, which is a huge bonus. The researchers at IRL are following a number of strands of research: improving the yield of islets from donated pancreata (they only get about 50% yield at the moment), improving the vascular development and survival of implanted islets, and enhancing the immune protection of islets. They are also thinking about different sites for implantation - the pancreas is deemed too 'brittle' for implantation, which is why the liver is used, but there are other options that may be more successful, such as the intestinal submucosa.

Extraction of islets is quite brutal, so it makes sense to try to improve their 'health' before transplantation. It has been found that they survive better if held in a rotational suspension rather than allowing them to settle in culture. Next, ways to enhance vascularisation include stimulating secretion of vascular endothelial growth factor (VEGF) through incubation of islet cells with various drugs that not only increase VEGF expression but have also been shown to up-regulate beta-cell insulin secretion (the 'glitazones' or thiozolidinedione family).

Four experimental results
Fluorescence immunostaining for insulin (red – TRITC) and VEGF (green – FITC) in human islets maintained in (a) SC, (b) SC TZD, (c) RC and (d) RC TZD.TZD: thiazolidinedione; SC: static culture; RC: rotational cell culture; TRITC: tetramethylrhodamine isothiocyanate; VEGF: vascular endothelial growth factor; FITC: fluorescein isothiocyanate.
The immuno-protective angle seems to have arisen by one of those chance thoughts that the senior researcher seems to have had while doing a crossword or brushing his teeth or something - how is a developing foetus protected from the immune system of the mother? This has resulted in a series of experiments using adult stem cells from the amniotic membrane, which they collect from the nearby hospital following donations from women having caesarian sections. Sticking some of these cells in with the islets (nothing sophisticated, just mix them together) seems to have resulted in some useful fusing of the different cells, and may lead to a new line of research.

Progress is slow in research, and while I thoroughly approve of what they do, I can't imagine doing it myself - hardly any human contact, tens of years before results of experiments are any practical use. They also struggle for funding, ethical approval of research, and lack of donor material. Research labs are only third in line for any pancreas donation - first are medical centres that do whole pancreas transplants, and second are those that perform islet transplantations on people rather than just doing research. So IRL ends up with the pancreases that nobody else wants.

We all sang rousing songs in the minibus on the way back (no, of course we didn't) but I was mystified by those of the party, and there were several, who had been on this trip more than once. The rate of progress meant that aside from the benefit of tea and biscuits and sitting down for an hour or so, there would have been little change since the last time they were there. But then, this group contains individuals that are like none I have ever met before.

* by far my best moment of the evening came when the lead researcher first used 'pancreata' as the plural of pancreas.

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