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.

Fav. Tracks: Zabriskie Point – Various Artists

zabriskie Zabriskie Point – Country Song (Pink Floyd)

This post brings the description of my current music collection to an end.  I have not included any of my classical music, but I think I have included all others.

This final collection of music from various artists is in fact the soundtrack to a cult film from 1970, which describes the development of the youth-based movement of the late 60s in the USA.  A total failure as a film, the beauty of Zabriskie Point is undoubtedly this music and especially the input from Pink Floyd.

This song starts off very much like some of the tracks from the film More, but after a while it turns to a more rock-based sound with a buzz effect on the lead guitar.  This turns back to the initial theme and so the tune repeats.  The lyrics are interesting and powerfully sung and there is clearly music development that makes the sound a little unusual for Pink Floyd.  The rock influence gets stronger toward the end of the track until a faded ending.  A very unusual piece of music from an unusual album.

The album tracks:

Heart Beat, Pig Meat Pink Floyd
Brother Mary Kaleidoscope
Dark Star [Excerpt] Grateful Dead
Crumbling Land Pink Floyd
Tennessee Waltz Patti Page
Sugar Babe The Youngbloods
Love Scene Grateful Dead; Jerry Garcia
I Wish I Was a Single Girl Again Roscoe Holcomb
Mickey’s Tune Kaleidoscope
Dance of Death John Fahey
Come in Number 51, Your Time Is Up Pink Floyd
Love Scene Improvisations [take 1] Jerry Garcia
Love Scene Improvisations [take 2] Jerry Garcia
Love Scene Improvisations [take 3] Jerry Garcia
Love Scene Improvisations [take 4] Jerry Garcia
Country Song Pink Floyd
Unknown Song Pink Floyd
Love Scene [Version 6] Pink Floyd
Love Scene ][Version 4]

Fav. Tracks: Yesterdays Gold Vol. 13 – Various Artists

alb_224404_big Yesterdays Gold Vol. 13 – Cathy’s Clown (The Everly Brothers).

This MP3 download has some classic oldies from the 60s, but was primarily bought for this one song – Cathy’s Clown.

The sound is instantly recognisable as The Everly Brothers and is typical of the pop ballads of the early 60s.  It quickly becomes a sing-along track and is easy to listen to at anytime.  One of the classics of the era.

 

The album tracks:

The Everly Brothers – Cathys Clown
Roy Orbison – Crying
The Coasters – Along Came Jones
Clyde Mc Phatter – A Lovers Question
Gene Pitney – The Man Who Shot Liberty Valance
Ray Charles – Georgia On My Mind
Fats Domino – I Want To Walk You Home
Connie Francis – Mama
Brook Benton – Frankie and Johnny
La Vern Baker – I Cried A Tear
Jackie Wilson – Dogging Around
Bobby Darin – Wont You Come Home Bill Bailey

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