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).

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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.

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Fav. Tracks: The World of Progressive Music – Wowie Zowie – Various Artists

100 The World of Progressive Music – Wowie Zowie – Train to nowhere (Savoy Brown).

This vinyl album, from the Decca label, is another example of a sampler album introducing the labels various Progressive Rock artists (Decca were probably the least well known for this genre at the time, but eventually produced several major bands through Decca Deram).  The album was released in 1969 and has quite a few well known bands including Genesis, East of Eden and The Moody Blues.  Savoy Brown were a less well known (at least in the UK) London band who formed in the mid sixties, but later moved to the USA.  My introduction to their music was from this sampler album and I really liked this track (for some reason I never got around to buying any of the LPs).

I love the unusual sound of the track, which is excellently complemented by the singing voice of Bryce Portius, but it is difficult to describe the sound of the music – it is neither blues nor rock and is maybe a portent of things to come!  This album is an indicator of how progressive Rock was to develop into many interlinked bands.

The album tracks:

Down at Circes Place – Touch
Where did I Belong – John Mayall
Train to nowhere – Savoy Brown
Voodoo Forest – Johnny Almond
Communion – East of Eden
In The Beginning – Genesis
Nights in White Satin – The Moody Blues
Computer Love – William R Strickland
Go Away, come back another day – John Cameron Quartet
Not Foolish, Not Wise – Keef Hartley Band

Fav. Tracks: Woodstock Two – Various Artists

jimi-hendrix-woodstock-two-4231451 Woodstock Two – Marrakesh Express (Crosby, Stills, Nash & Young).

This is an old vinyl double-album dating back to 1971 and is a second release of material from the famous Woodstock Festival and, as such, is perhaps not quite as good as the first album, but still has some important bands and music and remains an important recording of this historical event that gave birth to all other music festivals (and saw the development of the peace movement so tightly associated with hippies and the youth of the time in general).

Picking a favourite track from this album was not too difficult and I immediately chose this classic hit from the brilliant Crosby, Stills, Nash and Young.  I love the catchy tune and the lyrics are brilliant and tell the tale of that early 70s era.

Catch a bit more of the era with the closing song sung by most of the artists who appeared and featuring a track made famous by the musical stage play “Hair”

The album tracks:

Jam Back at the House Jimi Hendrix
Izabella Jimi Hendrix
Get My Heart Back Together Jimi Hendrix
Saturday Afternoon/Won’t You Try Jefferson Airplane
Eskimo Blue Day Jefferson Airplane
Everything’s Gonna Be Alright Paul Butterfield
Sweet Sir Galahad Joan Baez
Guinnevere Crosby, Stills, Nash & Young
4 + 20 Crosby, Stills, Nash & Young
Marrakesh Express Crosby, Stills, Nash & Young
My Beautiful People Melanie
Birthday of the Sun Melanie
Blood of the Sun Mountain
Theme for an Imaginary Woman Mountain
Woodstock Boogie Canned Heat
Let the Sunshine In Various Artists

Fav. Tracks: While My Guitar Gently Weeps Disc 2 – Various Artists

whilemyguitar%20lge While My Guitar Gently Weeps Disc 2 – Cocaine (J.J. Cale)

The second CD of this small boxed set is another collection of wonderful guitar riffs and tune.  However, picking a favourite was, again, very easy for me as this track (cocaine) is one of my all time favourite blues track.

The riff is instantly recognisable and a great complement to words that I think are an interesting reflection of the world.  This is a really good foot-tapping tune and one everyone should have in their blues collection, whether it be Clapton’s version of this one  by JJ Cale.

The album tracks:

Big Log – Plant, Robert
Purple Rain – Prince
Road To Hell (part 2) – Rea, Chris
Parisienne Walkways – Moore, Gary
Jessica – Allman Brothers
Woodstock – Matthew’s Southern Comfort
Sweet Home Alabama – Lynyrd Skynyrd
Turn To Stone – Walsh, Joe
Black Magic Woman – Fleetwood Mac
Hold The Line – Toto
More Than A Feeling – Boston
Guitar Town – Earle, Steve
Bad Case Of Loving You (Doctor Doctor) – Palmer, Robert
Jail Bait – Wishbone Ash
Cocaine – Cale, J.J.
Blue Guitar – Hayward, Justin & John Lodge
Going Home (Local Hero theme) – Knopfler, Mark
Whiskey In The Jar – Thin Lizzy

Fav. Tracks: While My Guitar Gently Weeps Disc 1 – Various Artists

whilemyguitar%20lge While My Guitar Gently Weeps Disc 1 – While My Guitar Gently Weeps (Jeff Healey Band)

This double CD is a wonderful collection of some of the best guitar work in recent rock history.  However, picking a favourite track from this first CD was relatively easy as the title track has always been one of my favourite pieces of music.

The introduction has a wonderful sound to it and really fits to the chorus and track title – the guitar really does weep.  The lyrics, in my view, are an amazing commentary on the world and the chorus easy to sing along with – just rock music at its best.

The album tracks:

After Midnight – Clapton, Eric
Love Over Gold – Dire Straits
Samba Pa Ti – Santana
Stuck In The Middle With You – Stealer’s Wheel
Keep On Lovin’ You – REO Speedwagon
Show Me The Way (live) – Frampton, Peter
Little Bit Of Love – Free
Right Next Door (Because Of Me) – Cray, Robert Band
Thrill Is Gone – King, B.B.
Sweet Dreams – Buchanan, Roy
Cryin’ Won’t Bring You Back – Green, Peter
Chance – Big Country
I Don’t Want A Lover – Texas
Shine Silently – Lofgren, Nils
Bird Of Paradise – White, Snowy
What’s Going On – Taste
Badge – Cream
While My Guitar Gently Weeps – Healey, Jeff Band

Fav. Tracks: The Very Best of MTV Unplugged, Vol. 2 – Various Artists

The Very Best Of MTV Unplugged 2 - FRONT The Very Best of MTV Unplugged, Vol. 2 – Wicked Game (Chris Isaak).

I am not sure how I came to this album, but I have a feeling I may have downloaded it to get this one track.  However, there are some other interesting tracks, some of which I had not heard before and others that were major hits.

I love the introduction to this track the guitar is superb and there is a great rhythm to the tune.  Chris Isaak’s voice is perfect for this song and he provides a real depth to the sound and that interesting shift in key is superb.  All in all a great track.

The album tracks:

Every Breath You Take Sting
Wicked Game Chris Isaak
Zombie The Cranberries
Imitation of Life R.E.M.
Layla Eric Clapton
Four Seasons in One Day Crowded House
Cornflake Girl Tori Amos
Have I Told You Lately That I Love You Rod Stewart
Like a Rolling Stone Bob Dylan
Human Behaviour Björk
Crazy Seal
Beds Are Burning Midnight Oil
Run, Baby, Run Sheryl Crow
I’m Ready Bryan Adams
In the Air Tonight Phil Collins
Don’t Let the Sun Go Down on Me Elton John

Fav. Tracks: Vertigo Annual: 1970 – Various Artists

VERTIGOANNUAL_GER2 Vertigo Annual: 1970 – Three Sisters – Affinity,

This double album (vinyl) is one of my all-time favourite “sampler” albums and is a wonderful illustration of how progressive music was developing quickly and being marketed in 1970.  The music on this album led me to buy several other albums by the featured artists, so it did its job very well, but it a collection of many of major bands of the time.  In picking a favourite track I feel I should avoid those bands that I have listed elsewhere and, so, I choose a piece of music that I think is very catchy and an example of rock music developing from progressive rock sounds, from a band that launched from The University of Sussex, produced a single album, but then disappeared.

I like the rhythm that opens the track and the way the lyrics echo the story of the witches from Macbeth.  The music has hints of Black Sabbath and I can imagine a powerful stage-act built around this (although, because the band mainly played universities, this probably would not have happened).

The Album tracks:

Elegy Colosseum
Handbags and Gladrags Rod Stewart
Half Baked Jimmy Campbell
I Don’t Know May Blitz
Mississippi Woman Juicy Lucy
In My Box Fairfield Parlour
Goin’ My Way Magna Carta
Three Sisters Affinity
Behind the Wall of Sleep Black Sabbath
Introduction Gracious
To Play Your Little Game Cressida
Elastic Rock Nucleus
One Way Glass Manfred Mann, Chapter Three
No Time Like The Present Bob Downes
Summer Breeze Dr Strangely Strange
Gypsy Uriah Heep