Introduction: A short history of my PhD

My dissertation title, for those of you who care, was ‘Rising Incidence of Type 1 Diabetes – autoantibodies and genetics in an evolving environment’. I started my PhD in Autumn 2009 after two years working as an autoantibody technician. *If you want to know more or check my factoids why not check out the Diapedia website where they are constructing a peer reviewed and referenced encyclopaedia of the disease(s)*. The associated posts are designed to give a bit more detail to introduce you to my subject area. See; Rising Incidence, Type 1 diabetes, Autoantibodies, Genetics, Environment. Not all the posts are up yet, as I write them I will link them together and link them in here.

Sciencey bit: Type 1 diabetes

First things first, what is diabetes?  Most people who have diabetes have diabetes mellitus which has to do with inability to regulate blood sugar. The sugar in question is glucose which is what cells use to make energy. Blood glucose is regulated by two hormones; insulin (which tells cells, including special storage cells in the liver, to take in glucose) and glucagon (which tells the liver to give back the glucose). In type 1 and type 2 diabetes insulin is unable to regulate glucose because there isn’t enough of it or the body doesn’t respond to it anymore. Insulin is made by beta cells (β-cells) which live in the islets of Langerhans in the pancreas, which is a little organ that makes a hormones (like insulin) and digestive enzymes. In T1D there isn’t enough insulin because the β-cells that make the insulin have been destroyed by the body’s immune system. It is, therefore, an autoimmune disease. The really interesting thing is that it is the β-cells that are destroyed by the immune system and the neighbouring alpha cells (that make glucagon) and exocrine pancreas (which makes the digestive enzymes) are left completely alone. This shows how good our immune systems are at destroying specific things.

 

Lots of children develop disease in their teens but children can be diagnosed as young as six months. Before this age diabetes tends to be caused by a ‘simple’ genetic problem. That is, simple in the sense of affecting only one gene, not necessarily simple to identify or treat. Individuals with T1D have to inject insulin to manage their blood glucose. Insulin was identified and extracted in 1922. However despite the effectiveness of this treatment it still isn’t as good as the homeostasis afforded by the β-cells. This means that people with diabetes can experience a host of complications later in life including blindness, kidney and heart disorders, and lack of circulation in the extremities. This is one of the reasons why it is so important to research this area. There are of course lots of medical research that could help a person with diabetes. For those who have progressed to complications you want to be able to maintain their eyes, kidneys, hearts or toes for as long as possible. For all people with diabetes you want to help them maintain their blood sugar the best they can so that they are less likely to develop complications and enjoy their current life. We therefore have people researching new insulins that can better mimic natural insulin release, people working on artificial pancreases, and people working on transplanting pancreases or islets of Langerhans (where the β-cells live). The other tactic to employ is to try and stop people getting diabetes at all. This doesn’t really help those people who already have disease but IF we were successful it would clearly be the best thing. This ‘if’ is a big ‘if’, but there are lots of people who are trying to make it happen and this is where my work fits in. Can we predict who will develop disease? Can we understand why and how disease happens? Can we find a way to stop disease? The answers are; yes - to a point (see the autoantibody and genetics sections), kind of, and one day!

Sciencey bit: Rising Incidence

The incidence of disease in the UK in under 15s is something like 20 per 100,000 per year. Prevalence is often quoted at 0.4% (four in every thousand) but I challenge you to identify the paper where this is actually calculated. Incidence is one of those words you kind of have a feel for without actually knowing quite what it is. It is the measure of NEW cases of a disease and is often measured per 100,000 (people) per year. This is distinct from prevalence which is about the total number of people with a disease. As you can imagine one problem with measuring incidence is knowing how many people have the disease, the other is having an accurate idea of how many people make up the general population. You could say 1 out of 100 children were admitted to A&E  because of new onset type 1 diabetes (hence forth abbreviated to T1D for the sake of my sanity) but it wouldn’t really tell you anything about anything except that A&E department (the numbers used here are as an example and are based on no factual information). You might think we have a good record of who has T1D, after all it is fatal if untreated, but when you start including new adult cases of T1D you start to muddy the water with cases of type 2 diabetes. ‘Adult Cases?’ I hear you cry! ‘but T1D is a disease of childhood, isn’t it?’. Actually not so much; as I understand it the majority of individuals actually develop disease after the age of 15 but per age group the incidence is lower in adults (at least with our current definitions of T1D which are slightly circular). For the reasons mentioned above incidence of diabetes is easier to calculate in some places (generally those with better developed health care) and in children. Even in western countries however national registers of diabetes are few and far between therefore another important part of calculating incidence is to try and figure out who you might have missed. This is done by cross checking the cases you found with cases identified by an independent source and is known as secondary ascertainment. If you see incidence without ascertainment be suspicious, very suspicious! The other challenging thing about incidence is that you get a lot of variation year on year. This means you need data from a lot of years to get a real sense of the variation and any change in the average incidence.

 

So now we are caught up on the tricksiness of incidence calculating what is all this about incidence rising? Over the last 30-40 years we have started to get some good data collected over a number of years on the incidence of disease in children aged under 15 years. Studies of the incidence of disease have been spearheaded by a European study (EURODIAB) and a worldwide study (DIAMOND) which have analysed data from a number of countries simultaneously. These studies have shown almost universal increased incidence of disease in childhood at an average rate of 3-4%. Of course that is a increase in a small starting incidence but it is an increase that adds up; the most dramatic data are from Finland (which is also the country with the highest incidence of disease) where incidence increased from 31 per 100,000 per year to 64 per 100,000 per year in just 25 years (1980-2005). The increased rate of disease is most obvious in children under the age of 5 years old. There are two possible explanations 1) that disease is becoming more common in all age groups, 2) that individuals are developing disease at an earlier age. We really need good data on disease in adults to figure out which of these possibilities is true and as yet no consensus has been established.  So though I say ‘rising incidence’ this is actually short hand for ‘rising incidence of type 1 diabetes in under 15s in ‘more developed’ countries because I have no idea about incidence in adults or most of the world’s population’. There have been a few reports of a plateau in incidence but as yet none have been sustained.

 

Why is incidence rising? One might suppose that more people with diabetes are now surviving long enough to reproduce and so maybe we are passing more disease on to new generations genetically (for more info see the genetics section). In a small way this is true but the increase in incidence is too dramatic to be caused by proliferation of ‘at risk’ genes. Some researchers have looked at genetic risk in populations of individuals who have been diagnosed with disease at different time points. These studies show is that people who are diagnosed more recently have (on average) less genetic risk for diabetes. This means those with high genetic risk are still developing disease but more people with less genetic risk are now developing disease. Why might this be happening? Pretty much all biology boils down to the product of genes and environment. So if the genetic contribution is reducing the environmental contribution must be increasing. What might this environmental factor be? Short answer, we don’t have a clue. For some more ideas see the environmental factors post.

Lean not on your own understanding...

This week I have been mainly working! So there aren't any particularly exciting photos. I did however go to Costco on Saturday and, because my sister works at Costco in the UK, I took photos! This week I have succeeded in setting up a bank account and a PO box so I feel like I have achieved the main non scientific objectives of the trip.  I'm about to embark on my last week here till August. Wow it went by quickly. I have been working on a number of other posts during the week so quite a lot will go up today.

 

 

This week as I struggle with new knowledge I have been struck by Proverbs 3:5-6 "Trust in the Lord with all your heart, and lean not on your own understanding. Acknowledge him in all you ways and he will make your paths straight". As postmodern (?) people we are encouraged to lean on our own reason, think about stuff for ourselves, be our own people, be self reliant. As scientists we work as an international web of ideas, the accumulation of the blood, sweat and tears of generations of academics, but we are still encouraged to 'own' knowledge and lean on our own understanding of the facts. As a Christian I take a moment to remember that the weight of the world doesn't lay on my shoulders, that my understanding is a part but not the whole. I don't know it all and thankfully I don't have to!

Blown away by blown glass...

This is the street I'm staying on

My building is the one in the middle of the photo
on the left

Freeway park

Another week has passed in the blink of a coffee fuelled eye – I am going to miss the coffee machine at work. This week I also found ‘Tetley British Blend’ in the store ($3 for 80 tea bags) the USA isn’t quite a tea desert after all. This week at work I have been continuing to learn cell staining and flow cytometry. It seemed to be going ok to start with but every day I seem to kill more cells. The death of my experimental cells has been reflected in the number of brain cells I have lost to a fruitless struggle against the Mac computer I have been using for analysis. It has however been a lovely sunny week and I have the photos of Mt. Rainier to prove it! The fountains have also started flowing in Freeway park, I now understand the purpose of all the concrete, which I presume is a mark of Summer.

 

Mt. Rainier from the bus. It's quite hard to get a photo where you can see it!

On Saturday I had the day to myself and headed into Seattle centre for the afternoon. I decided to go over to the space needle for the first time. This gave me a good excuse to try the monorail.



Monorail (Downtown end)

Monorail (Space needle end)

Room 1 - experimenting with glass and fluorescence

Space needle!

I am waiting for visitors to venture up the space needle but. I had a good time in the gift shop! I couldn’t however resist the lure of the glass sculptures peaking up above the fence around the Chihuly Garden and Glass exhibition. I dutifully paid my $20 (yes it was a lot) and spent two hours staring so hard I made my eyes sore. Chihuly is from this region and produces beautiful glass installations.


Room two - inspired by native baskets

For more information go to chihulygardenandglass.com and/or enjoy the pictures... a picture speaks a thousand words so 30 pictures is getting on for a thesis!




 



Room 3 - inspired by the sea

Room 4 - Persian Carpet



Room 5 - inspired by nature



Room 6

Drafting out ideas



Room 7 - glass chandeliers




Room 8

 

There is no fear in what you’re going to face...

From the mundane (flat photos) to the glorious (this entry?) – God is in it all. Many years ago when I was still at Uni (that is doing my undergrad at Bath) I went to a wonderful little church called Hayhill Baptist Church. This was a lovely little church with a family feel and, at least when I attended, not too many students! Anyway, one of the things we did was have an ‘encouraging prophesy’ class lead by people from one of the other churches in Bath. I don’t know what your views on prophesy are but this was about making time to hear from God the encouraging words he had for your fellow Christians. We were all a bit nervous about this and tried our best but it was clear that those people who were leading the course had spent time growing this spiritual gift. At the end of each evening they spent time speaking to each of us, which they recorded for us so we could listen to what God was saying again and again. I only got to the sessions a couple of times but both times received encouragements that have stayed with me for the intervening years (which is actually only 7 years or so but I think I will be saying the same thing when I’m eighty!). So there are a couple of things they said that I’ve been reflecting on over the last few weeks.

 

First and foremost; ‘there is no fear in what you’re going to face’. She said this again and again as if to drive the message home, and I have always struggled with that. I feel like I fear pretty much everything I face – day in, day out – I fear. Then I got on a plane and flew across an ocean preparing to spend two years in a place I had never been, where I knew no-one. I prepared for the weight and crush of fear, for anxiety and homesickness. This is where God shows up. This is where he steps in. This is where I lean on a God who says ‘there is no fear in what you are going to face’ and does it, and I am without fear. I am provided for (largely through Laurie and John’s Christ centred hearts) and I know I will be provided for. The moral of the story is 1) God is good all the time, all the time God is good! And 2) guard the words you say and think carefully about the words you do not speak because you may be withholding an encouraging blessing.

Rent my flat or tell someone else to rent it!

Welcome to my flat:

One double bedroom ground floor furnished flat with garden. Purpose built flat with good size kitchen, bathroom, and lounge. On bus routes with easy access to M5.

Where? Henbury.

What?

·        Double bedroom

·        Ground floor

·        Furnished

How much?

·        £460 Rent (including water rates but excluding council tax and other bills).

·        Deposit £675 (can be paid in instalments).

When?

·        Available from August 1^st 2013.

·        May consider short term (2-3 month) rents but would prefer tenant likely to stay put for at least a year.

Furnishings and Fittings:

·        Single Bed (which can be disposed of if double bed required)

·        Wardrobes and chest of drawers

·        Arm chairs, Sofa, dining chairs, dining table.

·        Gas heating/hot water, gas stove top, gas fire in lounge.

·        Electric Cooker

·        Washing Machine, Fridge freezer, Microwave.

·        Bath and a shower (hopefully – I’m working on it!)

 

·    Mature garden, including small patio. Could be used for growing vegetables or flowers. Great for barbeques (if we have a summer!) 

·      Lockable shed – with gardening equipment, space for storing a bike.

·        Parking is on road, usually there is space directly outside flat.

Anticipated bills:

·        Council Tax (Band  A. £96 for 11 months (single person discount 25%)

·        Electric - currently paid by direct debit (around £15 a month)

·        Broadband (currently £25 a month)

·        Gas – on key card (estimated cost is seasonal. £40-£50 a month in Dec, Jan, Feb. £10-15 per month in June, July, Aug. Spring – varies). You may get a better deal if you shop around.

Possible optional extras (trying to find a home for my belongings):

·        My collection of sci-fi/fantasy books (floor to ceiling bookshelf) as you can see on the photo

·        Sewing Machine

·        Two man (really one man) tent with camping equipment.

·        DVD collection

·        DVD player and 21” TV (not flat screen)

·        Christmas tree and Christmas decorations!

Rental is at cost to Anna (interest on mortgage, content/buildings insurance, water bill rate) who will be in the USA. Yearly boiler services will be arranged by the Anna. Other repairs (due to wear and tear) will be paid for by Anna but should be organised by the tenant (e.g. fixing washing machine). The alternative is to get a letting agents involved and then the cost goes up. Generally contact with me will be through e-mail (to approve repairs etc.) but for emergencies I’ll provide you phone numbers for my family in Bristol.  

Bus routes:

·        On the 76 bus route - Cribbs Causeway to Hengrove, via Southmead Hospital, Gloucester Road and Bedminster.

·        On the 1 bus route - Cribbs Causeway to Broom Hill, via White Ladies Road, Temple Meads.

·        Close to the 54 bus route  - Cribbs Causeway to Stockwood, via Southmead hospital, White Ladies Road, Temple Meads.

·        Close to 40 bus route – Cribbs Causeway to Old Market, via Shirehampton and Avonmouth.