Genetics and Type 2 Diabetes

Diabetes-with-family-history-prevalence-city-20592 When I first diagnosed with Type 2 Diabetes (TD2) I immediately started to research the scientific literature for any clear genetic explanation of this highly prevalent disease, but I was unable to find any clear link between a specific genetic loci and occurrence of the disease; although, there were several papers making such links they were far from proving any such link.  However, a recent article in Scientific American (October 2015, pp56-59) has suggested one possible explanation of the growth of TD2 and a genetic cause that predates the evolution of Homo Sapiens!  Reflecting on this article I can understand how I would not have come across this explanation as the research has always been linked to a different disorder – Gout, or the “disease of Kings”.

Gout is caused by a build up of uric acid in the bloodstream, which can then crystallise in capillary vessels leading to immense pain.  Uric acid is swiftly removed from most animals through breakdown by an enzyme called Uricase, but humans and many primates lack a functional form of the gene responsible for production of this enzyme.  Apparently, the loss of function of this gene occurred some 15+ million years ago when a series of nonsense mutations inactivated the gene (Oda et al. Mol Biol Evol 2002;19:640–53).  The article proposes that the selective pressure for the loss of Uricase activity begins when apes moved from Africa to Europe, which at first provided a plentiful environment with a sub-tropical climate providing bountiful supplies of fruit for their diet (particularly figs).

All_palaeotemps

However, this period saw the beginning of climate cooling and this drier cooler weather changed the European vegetation from a rich broadleaf forested area toward a savanna-like environment, with much less fruit available and much of this fruit (especially figs)now becoming seasonal and quite scarce during winter.  As cooling continued these European apes began to starve, therefore, the loss of the Uricase gene must have provided a selective advantage (Hayashi et al. Cell Biochem Biophys 2000;32:123–9).  The normal mammalian reaction to periods of starvation is to produce fat (e.g. for an energy supply during hibernation, or to provide sufficient energy to survive winters).  However, during prolonged periods of starvation foraging for food must continue, especially for primates that do not hibernate, and for this to be successful glucose is required by the brain.  This is achieved by an “insulin-resistance” effect.   The clue to this selective advantage lies with the fruit-rich diet that the apes in both Europe and Africa were consuming – digestion of fructose leads to production of uric acid and researchers have found that uric acid can trigger this switch to “insulin-resistance”.insulin-resistance The researchers proposal is that the loss of the Uricase gene led to a gradual development of the ability to switch to converting fructose to fat providing a better chance to survive food shortages during winter.  They also propose that these European apes may have brought this major selective advantage back to Africa as they migrated back to avoid cooling winters, they must have out-competed African apes and thus left the mutated Uricase gene that has been acquired by humans.

If this explanation of these genetic events is correct, we have a genetic explanation of TD2 – sometimes known as insulin-resistance – and what we have now is that processed foods, which often contain corn syrup, or table sugar, that are extremely rich in fructose, are being turned into fat because of the elevated uric acid levels in our bloodstream.  It would be exciting to think that new drugs could be developed against uric acid production, which might help reduce obesity and TD2.  Genetic Engineering may even hold the possibility of restoring Uricase production in the distant future.  In the meantime, as I have said before we must aim to increase regular exercise, reduce sugar intake and aim to make fresh fruit our only supply of fructose.  The antioxidants available in fresh fruit help to reduce many side effects of excess uric acid and reduce multiple diseases.

However, from a personal viewpoint I am left with something of a mystery as this genetic explanation does not explain familial occurrences of TD2, something I have personal experience of!  The best link between TD2 occurrences in families and an observed disorder is that TD2 is tightly linked to β-cell dysfunction in the pancreas (O’Rahilly, S.P. et al.  The Lancet , Volume 328 , Issue 8503 , 360 – 364), which is associated with insulin resistance (Kahn, 2003.  Diabetologia 46, 3-19), but the nature of this genetic link is complex and confused and involves amyloidosis of insulin.  A detailed description of this will follow.

Corned Beef Hash

DSC00002This recipe is a classic quick and easy meal that can be prepared and cooked in less than 30 minutes, it is based around using sauté potatoes rather than the more traditional mashed potato and this tends to make the meal look less mushy.  The amounts and variety of herbs and spices can be varied to suit your own taste – experimentation is everything!  The recipe below serves two people.

  • 1 340g tin Premium Corned Beef.
  • 1 tin of new potatoes (or freshly boiled new potatoes that have been scrapped and boiled for 15 min).
  • 6 small off the vine tomatoes.
  • Half a fresh onion, chopped into small pieces.
  • 1 finely chopped fresh clove of garlic.
  • Freshly ground red and black peppercorns.
  • Dried oregano.
  • Dried rosemary.
  • 1 tablespoonful of vegetable oil.

Preparation

Chop the onion into small squares.

Slice the potatoes across their width so that the slices are about 4-5mm thick.

Cut the tomatoes into quarters.

Cut the corned beef into cubes about 2cm across.

Cooking

I tend to use a wok to cook this, but a large frying pan will also work.  Place the oil in the wok and heat until medium-hot, add the chopped onion and garlic, which should sizzle immediately, and fry until lightly browning at the edges.  Add the potatoes and sprinkle them generously with the herbs and pepper (the potatoes should be generously covered with the ground pepper) and sauté until the slices of potato are heated through.  Add the corned beef and stir-fry until the cubes of corned beef soften, add the tomatoes and continue to stir-fry until the tomatoes are heated through.  Serve on a hot plate (with brown sauce if you are not diabetic).

The 44th Meeting of TOFC – The Old House at Home, Havant

old_house_at_homeThis was our third visit to The Old House at Home and it remains a firm favourite for many.  We booked for fifteen in advance, but as often happens these days we ended up being a larger gathering – 19 in this case.  We were setup near the back of the pub (near the kitchen) where we were last time and this area allows some expansion if necessary and we made good use of that capability.  In effect we used the lower long tables and three tall tables, which meant we were broken into smaller groups, but I think that helps conversations.

We had one new face at this meeting and a few who we haven’t seen for a while, which is always good for the atmosphere.  I certainly has a few good chats and a slightly political debate (ah well!), but all very enjoyable!  It looked to me like everyone else also enjoyed the day.

We were slightly late starting to order the food – we were delayed when Southern Trains cancelled the 11:13 and then pulled the 11:35 onto the wrong platform (which was already occupied) and consequently took several minutes just to unload the passengers through the one door on the ne carriage that was at the platform!  Still, once the order went in it didn’t seem to take too long for the meals to be served and as far as I could tell everyone got the meal they ordered.  My own personal view about Fuller’s pubs is that they are quite expensive and the food, on particular, is expensive for what you get.  that is certainly the situation here and my fish and chips were nice enough, but at £8.95 not cheap.  The beer that I had was HSB and that was good, but also not cheap.

All in all I still like this pub, but I think it doesn’t quite work for us as such a large group – not so much a space problem as an organisation problem – it is quite a drain on the kitty and makes it difficult to ensure fair access to the funds for everyone.  I think we may have to make more frequent visits to Wetherspoons in order to boost the kitty if we are to keep this gathering going along the current lines!

Thursday 27th February–More DIY

Up early again – in case they delivered the wood early – in fact they came about 10:30, so I could have had more time in bed!  It was a strange situation with the guys from Wickes as they were supposed to take away the damaged wood, but they said they didn’t want it and suggested that I kept it.  Then they rang back to say they should have taken it after all, so will now have to come back tomorrow to collect (between 8 and 9 am), so another early start.

DSC_0006I spent most of today working on the shoe rack that i am currently building and I have now finished the first stage.  There is still quite a way to go and a lot of sanding the wood before I glue it, stain it and varnish it.  I will carry on with the second section over the next few days.

I managed to watch some of the film (Time Runners) I borrowed from the library (about half of it), it was a little confusing, but interesting – I will reserve judgement until I have seen all of it.

I made chicken tikka for dinner today, it is a long time since I made that, but it was okay – maybe needs less cooking in the new oven – it went well with the salad.

Finally, watched an exciting game of football with Spurs playing a brilliant second half after a woeful first half and then  poor start to the second half.  Three goals in 13 min was very impressive.

Saturday 22nd February–Trip to London

Hilton London BridgeAn early start to the day on Saturday as we off to London for an overnight stay at The London Bridge Hilton and then on to the grandson’s 4th birthday party early Sunday (10:30 am).  I was up making some sandwiches to eat on the train and packing a few items to take with me – tablets, Kindle etc! Although we got the Waterloo train from Southampton Central, I was surprised when we got there to see a train going direct to London Bridge (it was what is normally the Victoria train via Barnham), but it is a slower train so we stuck with our original plan.  So, we took a taxi down to the station for the 12:30 train to Waterloo, which was fairly easy and then we too the over ground train across to London Bridge from Waterloo East.  A five minute walk at the other end found us in The Hilton Hotel, very easy.  A quick check in and then we made our way to the room, which was very nice, reasonably well set out and an adequate number of electric sockets.  Probably my only criticism was one side of the room seemed dark and how to operate the air conditioning system was unclear, but I worked it out.

cote_restaurant_london_photo_chiswickAfter unpacking, we went for a stroll around the embankment and The More area until we found ourselves in a bar watching the tail-end of the rugby (boy was it noisy though), still England won!  Just across from the bar was a Cotes restaurant and we have always had a good meal in that chain of restaurants and we decided to book a table for the evening.  After changing, back at the hotel, Kathy’s son joined us for a drink and then the meal.  The food was good and I had a really nice smoked salmon starter, followed by belly pork and a glass of red.  despite being Saturday night we got a table easily, and had good service throughout – I remain well impressed by Cotes.

The 43rd Meeting of TOFC–The White Swan, Guildhall Walk, Portsmouth

The White Swan

This was our second visit to this old haunt since Wetherspoons sold the pub and a microbrewery company took over – Brewhouse and Kitchen – and knowing the layout I thought I would contact them to make a booking.  In fact, we couldn’t get an answer when we phoned, but an email got a very quick answer and we booked for 20.  When we arrived we found we were situated at the back left of the pub, okay but a bit closed off from the rest of the pub, but there was plenty of space we just needed to arrange the tables a little.  There was a little inconvenience in that the door to the kitchen was next to us and we had to ensure access, but otherwise we were fine.

Being a microbrewery there is always the chance that a brew is being made when you visit this pub and today we were lucky (unlucky?) enough to be there as a brew was being produced, so the pub had a distinct aroma of yeast and malt.

There was a good turn out of TOFC members (19), so it took a while to compile the list of lunches, buy beers and drinks and settle down, but it worked out reasonably well with us splitting into one main group and one satellite group.  Once again it was nice to see old faces (a few we haven’t seen for a while) and at least one new face who has joined us.  Interestingly, we also saw a few faces of old colleagues from The University who had popped in for lunch (nice to see some traditions carry on).  I am pleased that everyone is still enjoying these events and that their popularity is growing, I just hope we can find enough new places to visit in 2014.

The menu has some unusual items (Chilli with chocolate in it!) and seemed to be reasonably popular – the Chilli was quite popular, but not sure I could taste chocolate, maybe – and despite the pub being busy, the food arrived after about twenty minutes and was very tasty.  I didn’t hear any complaints, just a slight uncertainty as to whether we got one too many meals (we didn’t).  So, so far so good and I have to say I like how they have set this pub up – I even got used to the smell of wort being prepared.  We all tried one of the locally brewed ales, Troubleshooter, and it seemed popular with everyone.  This is definitely a place to visit if you haven’t been before and I was more impressed at this second visit than I was at the previous visit.

The 42nd Meeting of TOFC – back to The Lord Palmerston

The Lord PalmerstonThis meeting of TOFC is the first of the New Year and consequently the one where we spend the excess funds in the kitty.  For that reason we always choose a Wetherspoons as they provide best value for money and The Lord Palmerston in Southsea is a good size to accommodate a sizable group.  Unfortunately, they don’t take table booking (apparently too many people fail to turn up) so we had to grab some tables early.  In fact, we managed to get a couple of long table down near the food serving area, which allowed us to expand easily and was handy for the food when it arrived.

For my wife and me, the journey was a train through to Portsmouth harbour, which ran perfectly on time, and then the No 1 bus that dropped us of at the top of Palmerston Road – so a relatively easy journey from Southampton.

As usual with this “free” event, we had a good turn-out (19 eventually) and there was already a good crowd in the pub by the time we got there with the kitty!  We quickly settled in and paid back those who has bought a round (that always goes down well) and then started to order food.  In between food orders there were a few different beers bought at the bar and, as usual for this pub, there was a good choice of different real ales.  The food order went in about 20 min after we arrived and the food was served very quickly afterwards.  I was not alone in saying how well Wetherspoons manage big food orders these days and everyone seemed to get there food quickly and without problem.

Once again there was good mix of people and, this time, we even found a new recruit in the pub – he mentioned to me that he remembered our Friday meeting from when we were all at work, lol!  Everyone seemed in good spirits and we chatted about everything from The Ashes (a bit depressing) to memories from work (distant!) and there was a good amount of mixing of people to improve this chatting.  All in all a good day and still some kitty left over!