Wednesday, 15 February 2017

Treating diabetes mellitus: from ancient Egypt to the NHS

Over the past thousand years of medical progress, mankind has seen a slow but steady increase in human longevity. Though the occasion plague, famine or war will lead to a mortality peak in a generation, by and large each new wave of humanity is healthier than the last.

But this trend seems to be about to change. A study published in 2015 revealed that middle-aged white Americans are dying at younger ages than their parents for the first time in decades; and as with all trends, where the US leads, the UK and Europe are sure to follow soon after. In fact, there are many  studies suggesting that today's children may lead shorter lives than their parents.

To explain these trends experts have looked to two main factors – firstly “deaths of despair” such as opioid overdoses, suicides and the complications from long term alcohol abuse. In 2015, 52, 000 Americans died of drug overdoses alone, more than died per annum of HIV/AIDS during the epidemic's peak years in the mid 90s. Almost half of these deaths were due to opioid-based drugs, such as heron or the much stronger synthetic opioid fentanyl.

Secondly a more recent study has linked diabetes to the increase in American mortality. Whilst in 1958 only 0.93% of the US population was diagnosed diabetic, now 7.02% (nearly 30 million people) of the country live with the disease. The number has grown three-fold since the early 1990s, rising with the ever increasing obesity rates.  Approximately 368 million people on Earth were living with the disease in 2013.

Most of these cases are  diabetes mellitus Type 2. This is what used to be known as “adult onset diabetes”, to differentiate it from Type 1 diabetes, which involves the auto-immune destruction of the insulin producing beta cells in the pancreas and usually begins in childhood.  Type 2 diabetes now makes up 90% of all diabetes diagnosis  in Europe and is seen increasingly in young adults and children.

Type 2 diabetes is associated with a ten-year reduction in life expectancy, and is though to be an under-reported cause of death, likely affecting life expectancy trends. People with diabetes often have multiple co-morbidities such as obesity, high blood pressure, cardiovascular disease, and even cancer.

Diabetes was one of the first diseases that we can recognise as described in an Egyptian manuscript from c. 1500 BCE. They mention “too great emptying of the urine” and that the urine would attract ants. This is due to the high levels of glucose in the urine seen in untreated diabetics. These first cases are believed to all be Type 1.

Type 1 and type 2 diabetes were described as separate conditions a thousand years later, in India, by the doctors Sushruta and Charaka, with Type 1 being associated with youth and Type 2 with obesity. The name “diabetes” was given by the Greek doctor Apollonius of Memphis in 250 BCE, meaning “to pass through”.

So throughout historical times, both types of the disease were recognised, although rare, and treatments were generally unavailable. Aretaeus of Cappadocia offers a list of symptoms of diabetes, although no treatments and notes “life (with diabetes) is short, disgusting and painful”.

However by the late 19th Century the idea of a low-carbohydrate diet was realised. Whilst under rationing in Paris during the Franco-Prussian war, French physician Bouchardat realised his diabetic patients were faring somewhat better. This lead to some doctors going so far as to keep their patients under lock and key to prevent them from breaking particularly restrictive diets.

In 1889 Germany, Oscar Minkowski and Joesph von Mering removed the pancreas from a dog and saw the poor animal developed diabetes. The protein insulin was eventually identified as being the key to blood sugar control in 1921. Sir Frederick Banting and Charles Best went on to purify insulin from cows and successfully treated a 14 year old boy with Type 1 diabetes in 1922.

Advances were made rapidly, in 1936 the two types of diabetes were made distinct from a treatment perspective and in 1944 a standard insulin syringe was developed. The structure of insulin was first determined in 1951 and first genetically engineered, synthetic human insulin for use in patients was produced using E. coli recombinant expression in 1978.

Since then, there has been huge amounts of progress in the treatment of diabetes, both Type 1 and Type 2, including the introduction of the blood glucose meter and the insulin pump. Short and long-acting insulin derivatives that stem from work done within the York Structural Biology Laboratory at the University of York are now the standard treatment for many Type 1 diabetes patients worldwide.

Researchers at the University of Pennsylvania looked at the prevalence of Type 2 diabetes in the US population and looked at the increased risk of death adults ages 30-84. They calculated that, while diabetes was listed as the cause of death in 3.7% of cases, it was more likely to the underlying cause in almost 12% of the total deaths. Amongst the obese cohort alone, the death rate from diabetes was closer to 19%.

There are now many drug treatments available for Type 2 diabetes, however many have complicated side effects. Most disease management regimens focus on lifestyle interventions to lower various risk factors and maintain a healthy blood sugar level.

Annually, the NHS currently spends £8.8 billion (over 8% of its budget) treating Type 2 diabetes and its complications – from outpatient services to amputations. On a societal level too, Type 2 diabetes has a huge impact on levels of absenteeism and early retirement as the various complications of the disease effect the suffers lives.

Prevention of the onset of Type 2 diabetes is the ideal solution from a healthcare prospective, and it can be achieved with both lifestyle changes and medication. Patients with prediabetes who go through lifestyle changes alone (weight-loss, increased physical activity and quit smoking) can reduce their risk of developing Type 2 diabetes by 50 to 60%.

Although it has been known for some time that obesity and the associated co-morbidities are a leading factor in reduced life expectancy, researchers are hopeful that a focus on diabetes and specifically the control of blood sugar might help healthcare workers and policy makers to combat the trends in mortality statistics. 

An abridged form of this article appeared in Nouse 14/022017

Thursday, 2 February 2017

Food, your mood and how we choose

Get short tempered before lunch? Snap at people if you’ve skipped breakfast? Perhaps you are suffering from hanger – the combined effects of hunger and anger.

Self-control requires energy. When our energy levels are low, it follows that our control over our temper is reduced too.

As blood glucose levels drop, the stress hormones cortisol and adrenaline are released to drive us to find our next meal. Along with a chemical identified as neuropeptide Y, these combine to make people more aggressive to those around them.

The effects of blood sugar on aggression were measured in a 2014 trial investigating 107 married couples. In the first part, the couples used voodoo dolls and up to 51 pins to express the level of anger that they felt at their partner at that time, and the blood glucose levels of both was measured.

In the second half, the couples played a competitive game, after which the winner could blast the loser with a loud noise through a set of head-phones. As expected, the lower the blood glucose, the more pins and the longer the noise the partners received.

A 2012 study at Columbia University looked at case sentencing by judges and saw they tended to be more lenient first thing in the morning and right after lunch. On the other hand, this may have been more to do with the ordering of the caseload (shorter cases vs longer and more complicated ones) than the timing of meals.

The hunger hormone, ghrelin, which is produced in the stomach prior to meals and during fasting, has been seen to have a negative impact on the brain’s ability to make rational decisions. During an experiment at the University of Gothenburg in 2016, rats with a higher level of ghrelin (mimicking hunger conditions) behaved more impulsively and erratically.

However this study was done in rats, they can be a good model for humans, and more research is needed to confirm the effect is true in us. But perhaps for now be careful when making decisions on an empty stomach.

Wednesday, 1 February 2017

Launching a solution to the lithium-ion problem

YOU OFTEN find rechargeable lithium-ion batteries in phones, laptops, hoverboards and even planes and electric cars. They are light-weight, highly efficient and rechargeable; this makes them ideal for all sorts of gadgets.
In comparison to nickel-cadmium batteries, lithium-ion batteries are more reliable, hold charge for longer and can be built to be much smaller and thinner.

The components of a lithium-ion battery are much less toxic than those of other battery types, which may contain lead or cadmium. The iron, copper, nickel and cobalt of a lithium-ion battery are safe for landfill or incinerators. Yet, 25 years after their introduction to the market, there are still occasional reports of lithium-ion batteries causing fires in all sorts of devices, including a fire on-board a Boeing 747 flight in 2010 which killed two people.
In 2016 2.5m Samsung Galaxy Note 7 smartphones were recalled due to a problem with their batteries, causing fires and injuries to many users. The recall of the Samsung phones was due to an engineering fault, the theory being that one part inside the battery was coiled incorrectly leading to an excess of stress on another single part. As more demands are made on the battery in any given device, engineers try to pack more power in to smaller spaces.
Within a lithium-ion battery, there are three main components: the positively charged cathode (a metal oxide), the negatively charged anode (graphite) and the liquid electrolyte, a solvent of lithium ions. The cathode and anode must be physically separated by a permeable wall and in very slim batteries this can be done by a polymer as thin as ten microns.If this wall is breached, it can lead to a process called thermal runaway. The battery gets hotter, leading to further degradation of the polymer, which causes the battery to heat even more. The flammable electrolyte can reach 500°C at which point it may ignite or even explode.
Simply adding flame retardant to the electrolyte solution would lessen the chance of fire but at the same time massively reduces the efficiency of the battery. To reduce the risk of a catastrophic fire, researchers at Stanford University have devised an automatic fire extinguisher for lithium-ion batteries. Yi Cui and this team have produced a thin polymer capsule that contains a fire retardant. If the battery overheats to the point that the polymer shell melts, the miniature fire extinguisher is automatically set off and the fire retardant released into the battery.
If these safety devices can be shown to work on a large-scale in a real world setting then it opens lithium-ion batteries to more widespread use in electric cars and aircraft. Currently a safer alternative to lithium-ion batteries is the solid state battery, where the liquid electrolyte is replaced with a solid which is far less flammable. However the inherent problem with the solid state battery is that it takes an incredibly long time to charge – negating most of its useful potential in cars and electronic devices.
Still, it is important to note that lithium-ion batteries are generally extremely safe. The probability of the lithium-ion battery in your phone failing is less than one in a million – whereas the probability of you being stuck by lighting stands at around 1 in 13 000 – meaning that lithium-ion batteries remain a relatively safe and efficient option.

Published Nouse 24 Jan 2017

Friday, 20 January 2017

Skeleton Tree - Nick Cave and the Bad Seeds

I wrote this album review back in autumn 2016 for Circulation Magazine. I have shared it here as a variation in the blog style. Perhaps I shall include some more music here later. Imogen.

Nick Cave writes about death. He always has done. Death, destruction and mortality are ongoing themes across the decades of his work. Yet here in Skeleton Tree there is something more. Although all but one of the songs were written before the loss of Cave’s fifteen-year-old son (in a fall from a cliff near the family’s home in Brighton), the album recording was completed in the aftermath.
It is hard to separate the album from the tragedy that surrounds it, although this is what Cave himself asks us to do in the accompanying documentary film ‘One More Time With Feeling’. But even the opening line brings your mind snapping back to focus “You fell from the sky / Crash landed in a field / Near the River Adur”. Words written before the tragic event but somehow so painfully foreshadowing.
There is, however, a logical progression from the earlier work. The Cave motifs are continued, mermaids, the sea, Gothic horror and the exploration of mortality. There are tracks where Cave sings from the view of an unknown female character and then goes on to sing about the same character from an outsider’s perspective, watching the woman becoming unrecognisable.
Whilst, for the most part, the lyrics are the standard Nick Cave fare, it is the delivery that really makes the record bite. Gone is the rage and threatening creepiness that rang out in Cave’s voice in 2013’s album Push Away the Sky. Here the speech-singing feels vulnerable and lost over the floating, looping texture of the music. He sounds like he has aged so much in the intervening years. On the seventh track, ‘Distant Sky’, he is joined by Danish soprano Else Torp as he searches for peace and the soothing lullaby of her voice just sharpens the bite of grief.
The Bad Seeds are as experimental and hypnotic as they have ever been. The old jangling rock of the early albums is long forgotten and Warren Ellis leads the fascinating and at times unsettling waves of sound that underlie Cave’s piano and voice.  This is a band that known for impressive energy and wildness during live performances,  producing tracks like From Her to Eternity; the stripped back effect is disquieting, though there is still the occasional snap of discord to keep you hooked.
This is an album you will listen to from start to finish and then find yourself sat in the dark thinking about for hours later. Perhaps, unlike his earlier work, it is not one you will return to again and again, the emotional drain it takes even as an outsider is exhausting. And perhaps this is not an album for outsiders to enjoy as such. But as Nick Cave explains in One More Time With Feeling, life goes on around tragedy, and for an artist, life is making art.

Monday, 16 January 2017

Acupuncture: what’s the point?

THE UNIVERSITY of York has now become the first university in the UK to appoint a ‘Professor of Acupuncture Research’, after awarding the title to Dr Hugh MacPherson at the start of this month. Dr MacPherson works in the Department of Health Sciences and has a focus on researching acupuncture’s effectiveness for various conditions, explanations for possible mechanisms that might explain its working, as well as its safety and cost-effectiveness in a clinical setting.
Research into acupuncture in recent years has taken two approaches, use of “sham” needles (needles that withdraw into themselves so the patient is not receiving acupuncture but still believes that they are, placebo acupuncture) and trials on rats and mice. There have also been several large data reviews, such as that by White et al in 2002 who looked at 22 different studies of the effectiveness of acupuncture on smoking cessation and concluded it did not help smokers trying to quit.

Increasingly popular in the UK, acupuncture
Image: Wikimedia commons. A standard acupuncture needle.
is a major component of traditional Chinese medicine and involves thin needles being inserted into areas of the body. Techniques and practices vary from country to country, but the procedure is mostly used to treat pain. However in more recent years people have begun to claim that acupuncture has helped them with everything from weight-loss to allergies to quitting smoking.
However in 2010 a group from the University of Rochester Medical Centre in New York induced pain in adult mice and then inserted (and rotated, ouch!) needles just below the mouse’s knee every five minutes for half an hour. These mice appeared to show a reduction in discomfort by 60%. Obviously this is somewhat different from the acupuncture that you or I would experience at a clinic, but, combined with some research from Kyung Hee University in Seoul that showed stimulation with needles reducing inflammation in rats with spinal cord injury, there is some data that drives more research into the medical viability of acupuncture.
Meanwhile, in humans, the placebo effect is a powerful thing, and hard to account for. A 2014 Nature Reviews Cancer review article published data showing patients reacting equally well to sham needles as to the real thing There is some debate as to whether “sham acupuncture” can ethically be used on elderly patients seeking treatment for osteoarthritis or if it is deception and thus unethical.
There are few dangers from acupuncture as such, as long as it is performed by a professional using sterilised needles. As such, some may argue that, even if the effect is purely placebo, perhaps for some patients as a pain management approach this would be more effective, safer and certainly cheaper than long-term drug treatment.  Nonetheless until there is sufficient evidence to support the use of acupuncture in the place of conventional medical treatment, it should not be offered in its place.

Published in Nouse 22/10/16

Sunday, 15 January 2017

The fight to resist antibiotic resistance

WHEN SIR Alexander Fleming received the Nobel Prize for Medicine in 1945, for the discovery and isolation of penicillin (jointly, with Ernst Boris Chain and Edward Abraham who discovered how to concentrate the drug and proposed the correct structure), he gave an interview  in which he predicted the situation we now find ourselves in.
“The thoughtless person” he declared, “playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penillin-resistant organism.”
Image: Pintrest
Image: Pintrest
Throughout the Second World War, penicillin was used to treat soldiers with infected wounds as well as bacterial infections such as pneumonia, syphilis, tuberculosis, gangrene, and gonorrhoea. Now most strains of gonorrhoea are resistant to penicillin, as well as other first line antibiotics such as tetracycline, and fluoroquinolones. Some multi-drug resistant strains are even resistant to cefixime, a broad spectrum antibiotic; it’s now no longer recommended to use this family of drugs to treat the STI in case resistance develops in more strains.
Whenever anyone undergoes a surgical procedure they are given antibiotics to reduce the risk of developing bacterial infections that can lead to sepsis. As more and more antibiotic-resistant bacteria develop, the number of people in the UK dying from antibiotic resistant infections will increase. In 2015, 44 000 people in the UK died from sepsis, compared to  35 000 from lung cancer. As more and more antibiotics are rendered ineffective, we risk returning to a world where a simple operation like an appendectomy is a life-threatening risk of infection.
In September, all 193 UN member states agreed to combat the threat of antibiotic resistant bacteria. This was only the fourth time in the history of the UN that they met to discuss a health subject. Margaret Chan, director general for the World Health Organisation (WHO), spoke at the event, calling for medical providers to rely less on antibiotics for disease treatment, and for more innovation in antibiotic development.
Only two classes of antibiotics have reached the market in the last 50 years. There is little profit seen in their discovery. It’s not a sound investment to create a drug, costing in the hundreds of millions, only to have to tell people to refrain from using it in large quantities in case resistance develops. Citizen science programs, such as Swab and Send created by Dr Adam Roberts at UCL, look to harness the energy (and financial backing) of the general public in the hunt for new antibiotic compounds.
There are other uses of antibiotics that we can now curtail. In the US, 80 per cent of all antibiotics sold are used on livestock to promote animal growth. Most of these drugs are often given at a sub-clinical level (i.e. a dose too low to combat a disease) so some bacteria in the animal are killed off but those that are naturally slightly resistant survive to multiply and mutate. This also has the effect of flooding surrounding land with waste run-off still filled with antibiotic compounds. Not only are the animal pathogens becoming more and more antibiotic resistant but the frequency of antibiotic resistance in other bacteria (such as those found in the soil and waste water) increases. The use of antibiotics to promote animal growth was banned by the EU in 2006, though it wasn’t completely phased out until 2011.
Tackling the increase of antibiotic resistance may seem daunting, but the signatories to the UN declaration agreed with the WHO to commit to innovation in antibiotic development, increase public awareness of the threat of antibiotic resistance and to develop regulatory systems for human and animal antibiotic use. As individuals we can play our part by only taking antibiotics when prescribed by a doctor, and always finishing the entire prescription, even if you start to feel better. You should never share an antibiotic prescription with another, or use up a left over prescription; even if you think it is for the same complaint. And remember, antibiotics will do nothing for a viral infection, so are unlikely to help if you have a sore throat or a cold!
Published in Nouse 1/11/16

Saturday, 14 January 2017

The Pill and depression: a correlation we cannot ignore

ON SEPTEMBER 28, a team of Danish scientists published the results of a six and a half year- long study linking hormonal contraception with depression. This is the largest study of its kind; a total of 1,061,997 women aged 15 to 34 participated. The study included women taking both kinds of oral contraceptive (combined and progesterone only), users of a patch (norgestrolmin) and users of users of a levonorgestrel intrauterine system (brand name Mirena® in the UK).
Depression, noted in the study as either a filled prescription for antidepressants or a recorded diagnosis by a medical professional, affects 2.6 in 100 adults in the UK every year, according to Mind, a mental health charity.
From the data gathered in Denmark, it seems that taking the combined pill increased the risk of a woman aged between 20 and 34 being prescribed antidepressants by 23 per cent.  A levonorgestrel intrauterine system appears to increase the likelihood of a depression diagnosis by 40 per cent.  The largest increase for both diagnosis of depression and prescription of contraceptives were seen in users of the hormonal patch, with a 100% increase in recorded depression signs.
Incidents of depression in teenagers (aged 15 to 18) taking the combined contraceptive pill who had no previous experience of mental health issues increased by 80% – from 1% in the general population of younger women to 1.8%.  Why the impact is greater on younger minds is not clear, but the NHS currently pushes longer term contraception to young women and perhaps this many lead to more GPs taking more time to discuss alternative contraception methods with their patients.
For those who have experienced mood-affecting side effects of hormonal contraceptives, this research couldn’t come soon enough. In fact, mood changes are one of the main reasons women stop taking the pill within the first year. Many women have felt that their concerns and experiences with the psychological and emotional problems from the prescription have been too easily dismissed.
However it should be noted that this is only a statistical analysis of the data, and though the research team did control for many variables it cannot yet be said what causes the link; correlation is not causation.
There are some things however that are not up for dispute. Depression is very real, and if you are concerned about yourself or others then please seek out help.

Published Nouse 7/10/16