More Drugs for Diabete's - Back to the Future?

Way back in the mists of time, chemists discovered a glycoside compound from the bark of apple trees that had a profound effect on glucose disposal in Diabetics. This extract, called Phlorizin, brought about glucosuria, which is the excretion of glucose in the urine. It also to some extent also caused polyuria (excessive urination). As these are often symptoms of  Diabetes itself, and as it was only 1835, it took a while for it to be viewed as anything that could be useful. As time went by experiments were undertaken to find a use but it was not until the 1970's that the mechanism of the compound was discovered and named. Sodium-Glucose Co Transporter-2  inhibitor (SGLT2)  is what it became and is the current theme of most research, for yet another drug for Diabetes.

I say yet another, because rather than using the original compound, which was in fact poorly absorbed in the gastro-intestinal tract, 'Big Pharma' needed to come up with a better 'mousetrap' in the form of a synthetic compound that could be patented, so that money could be made. Frankly, I find it a little alarming as the way it works is to inhibit the capability of the kidneys to 'save' glucose from being excreted in the urine. This a process discovered, that the kidneys perform, to conserve vital energy in the body and functions at a certain level. In Diabetics with high circulating glucose in the blood, the kidneys filter out the excess and do not conserve it all, as with normal humans, hence both glucosuria and polyuria are symptomatic in the Diabetic with low level control of hyperglycemia. What these new experimental drugs aim to achieve, is to enhance this phenomena, outwith the normal kidney function, so that the process 'kicks in' at lower levels of concentration. It does this by inhibiting SGLT2 in the kidneys.

 Astra-Zenica are conducting trials of their contribution to this wonderful idea at present; it is called  Dapaglifozin and is being developed in conjunction with Bristol-Myers Squib.What is important is the unintended consequences that may ensue from this, and the effect it may have on kidney function in the longer term. These may be obvious to many Diabetics with a grasp of their problems and the primary one is the enhancement of urinary glucose. All Diabetics are prone to urinary tract infections and genital fungal infections. This is largely because of the high glucose content of their urine, as bacteria and fungi feed on this. Low levels of glucose and acid urine inhibit this but Diabetics struggle to maintain this and, as a consequence get this type of infection and use antibiotics regularly as a result. This of course adds to the problems most already have and exposes them to long term or repeated incidents of UTI's for which ever more drugs are prescribed adding to the polypharma to which they are all subjected. To expose them to even more risk in this area seems somewhat counter productive.

In addition these drugs thus far have not displayed a great deal of success and are viewed very much as an 'add-on' protocol, for use with other hypoglycemic agents, such as metformin. They do enhance the performance of of these agents and lower HbA1c a little, but nothing startling. They also do enhance weight loss to a small extent, which is usually a good thing for a Diabetic, but, is it not about time, that science stopped its constant search, for a fix for something that is easy to stop. Reduce the glucose level at source, by stopping eating carbohydrates to any extent and Diabetics ease the burden on their already overburdened pancreas, and both the need or at least the volume of drugs needed is reduced or even eliminated.Of course that presents a problem for healthcare and especially 'Big Pharma'. So much money is at stake, both for them and for the NHS, which spends in excess of 10% of it's entire budget on Diabetics. The gravy train would halt and quite a few employees would no longer be needed. Turkeys voting for Christmas, I think not!

It also goes to show the panic in the Industry at the moment to come up with new ideas for drugs because patents are fast expiring and little is in the pipeline. There has been nothing of any significance, discovered  in Medicine in nearly twenty years, except more 'me too' drugs or new strains of the old one's. So they are turning once again to the old favourites such as cancer or diabetes. They've peddled useless or near useless and dangerous drugs to these cohorts for years, without any glimmer of a cure and it's costing them billions in compensation for some, such as Avandia, the cost of which has virtually wiped out GlaxoSmithKlines profits for the whole of the last year. Makes your heart bleed does it not?

It would be nice for a change to see research being directed at a cure, for some of these ailments or at least some acknowledgement that lifestyle changes can be just as effective as taking a store cupboard full of dangerous and often self-defeating drugs. Perhaps that is asking for the impossible.

At Last, Some Real Evidence of Efficacy of Omega 3's

This study , at last gives credence to the view that Omega 3 oil, in the right quantity and mix, alleviates some of the worst elements of depressive illness. (Sorry about the quality, but the cached version is free).

There have been a number of previous studies that were inconclusive from a scientific standpoint, but such interventions were viewed as relatively benign, except where high levels were consumed, when gastro-intestinal problems ensued.. The difference here is that the effect was dose related, with a high EPA to DHA level. And in a relatively low dose. It was also a high quality study conducted as a double blinded placebo trial. This is the 'gold standard' we all seek to give proof to a hypothesis. In addition, the cohort was suffering from major depression, not the "I'm feeling a bit low", type, but full blown serious depression, that can challenge life itself. Patients with co morbid anxiety symptoms were not shown to improve, however, so this group derived little benefit from the trial.

It ticks every box of study protocols, It was long term, of a size to be significant, but most of all the scientists involved went to great lengths to ensure even the placebo tasted the same as the genuine oil capsule. Sure, it was supported by the makers, in that they supplied product, but there is no patent on fish oils, so no real axe for them to grind, other than the satisfaction of proving a hypothesis, long held anecdotaly, but always never quite proven categorically. It is also significant that the cohort using other antidepressant drugs in addition to Omega 3's also derived little benefit.

Omega 3's have long been associated with a number of health benefits, quite numerous in fact. They are viewed as an anti-coagulant, an anti-hypertensive and have been associated with pain relief in arthritis. A number of studies for all uses have been undertaken, but most owe their origin to the study of nutrition in the Inuit of Greenland in the 1970's, when it was found that the Eskimo (Inuit) consumed large quantities of polyunsaturated fatty acids from their diet of fish. They also consumed even larger quantities of saturated fats as well, but that's another story. This diet even if confounded slightly by this, did seem to confer a protection from heart disease, stroke and hypertension. Consequently these long chain fatty acids became a 'must' for health.There are a few downsides, perhaps with consuming very large quantities, in that those prone to bleeding, say into the brain (hemorrhagic stroke), or with Type 2 Diabetes could worsen their symptoms by consumption, but on the whole it is relatively benign and is attributed with health improvements.

It is important that the EPA (eicosapentaenoic acid) content is somewhat higher than is found in most proprietary capsules with a ratio of 1050mg/d EPA to 150mg/d of DHA (docosahexaenoic acid) so some addition of EPA to a standard capsule regimen may be needed. But pure EPA capsules to enable this are now widely available. I also, personally feel, that 8 weeks is quite a short time for full benefit to be derived, as I found, certainly with my arthritis that real relief was not felt for almost three months. but that is my anecdotal experience. It seems, again anecdotaly, that the lessening of depressive episodes that I had been having, was more a side effect of taking Omega 3 for arthritic pain. The underlying problem of osteoarthritis, of joint deterioration, is of course not improved by this regimen, it is merely a means of pain control without the use of NSAID's.

Any one wishing to follow this protocol should engage with a medical practitioner, if at all possible, prior to commencement, and ensure that it does not, reduce or enhance the effect, of any medication already in use. This is especially important for people on Warfarin or Heparin protocols as the anticoagulant properties of Omega 3's can be pronounced in this cohort.

Evidence (or lack of it ) Driving Healthcare Objectives.

Healthcare has always been a Political subject. Back to the founding of the NHS, when Doctors railed against the deprivation of their 'Demi-God' status, by a State funded machine, to the Quality Outcome Frameworks of today, the Government, of the day,  has tried to manipulate the public, and to some extent Doctors too, to achieve 'goals' that they feel are cost effective or laudable. Some were self evidently beneficial, such as the, largely, but not entirely, elimination of killer diseases such as polio. But as time has elapsed and various Governments have come and gone, the systems that guide and govern the protocols for health, have been corrupted by the concept, that Medicine has the answer to all of mankind's ills; that a 'pill' can always be devised that will fix virtually any and every problem that humanity faces.

Science itself, has been corrupted in many ways. Studies are now undertaken almost exclusively by makers of drugs, prosthetics and diagnostic machinery. Very little 'peer review' of the outcomes or dangers is undertaken, except by those same makers. The manufacturers are now corporate entities that span the globe and have sales in excess of small (and not so small) countries. Their influence in our everyday lives has become both persuasive and pervasive and sadly, Medicine and Healthcare slavishly follows the hypotheses propounded by various segments of the Public Health Community, the Regulatory Bodies, the (so called) Charities, all, who stand to gain, from the perpetuation of a disease, condition or ailment, because elimination would hail their demise.

Each feeds on the other, perpetuating the appearance of scientific unanimity, about a health benefit for which there was probability, which becomes a certainty. Drugs only prescribed for seriously ill cohorts, then become beneficial for the 'worried well'. Protocols are invented to guide what we eat, drink, spend our leisure time embracing, all guided by dubious healthcare benefits, for which there is weak evidence of any good or useful outcome.  Powerful tools and organisations promote goals for which there is no real opposition, because it is not brooked, even in the face of incontrovertible proof that it is of no benefit, or worse, that it does harm. Possibility, becomes probability, and then certainty. Everything is presented as such; rational discussion is absent. Advice becomes diktat and all dissent is marginalised.

National policy currently advises us all that;-

Fat makes you fat and causes heart disease - not proven.
Cholesterol gives you heart disease - not proven, in fact proven to be false.
Statin's lower the risk of heart disease, in everyone - proven to be false.
Statin's lower heart attack risk in men with heart disease - now viewed as unlikely.
Hypertension (high blood pressure) is caused by salt - contradictory evidence therefore not proven.
Regular Mammograms save lives - in fact they do more harm than good.
Cancer rates are falling - not true, we are just better at extending the lives of those with it.
Heart disease rates are falling - as above.
Five-a-day lowers heart disease risk - in fact no benefit accrues.
Five-a-day lowers cancer risk - in fact there is little to no benefit except a small one for the vegetables only.
Green leafy vegetables lower diabetes risk - very little benefit.


The list is becoming too long, so I will stop now to save boredom setting in, but I can prove everyone of these tenets of healthcare to be either wrong or of so little benefit as to be virtually worthless. So how come the public doesn't know this and the bodies for whom we look to guide our health continue to peddle this worthless drivel? Well it's complicated. 'Big Pharma' and the food and drink industry have permeated all the agencies of the state and Politicians are so busy perpetuating power that they are indifferent to reason or dissent. Conclusions about healthcare are presented to the public with such forceful conviction that no balance now exists with the strength of the evidence that guides them or any that opposes it. There is a view that only the Politicians and the professionals that guide them, can weigh the evidence and they often view these protocols as inherently benign. So no harm then? Well er .. yes, but let not the truth guide you, if you are a Politician or 'Big Pharma' or the Food Standards Agency etc.etc.

Continuity of Care in the NHS (Joined up Medicine).

This tenet of Health care has long been regarded as the ideal, by most if not all Practitioners. It is the best way of safeguarding the patient from errors and mismanagement, be it in Hospital or the Primary Care Unit, such as the GP's practice. Most Trust's trumpet it as the pathway they all adhere to, but the reality is far from the rhetoric.The Kings Fund views it as being essential to the patient experience, whatever that is, and is researching and asking for input to achieving this goal. So what is it that is going wrong that prejudices patient safety and causes the almighty 'cock ups' that occur with alarming frequency in some of our alleged 'best' (sic) hospitals?

Well we do not have enough good Doctors or probably not enough Doctors at all. That is Doctors, who are either prepared to follow a patient through treatment to discharge, or ensure an adequate handover to another at the end of shift. And by good I mean adequately trained and motivated, not some 'wet behind the ears' youngster, virtually straight from medical school, tasked with the job, of taking care of numbers of wards, and patients on the night shift, with only a 'phone number to obtain Consultant backup. And of course with the knowledge, that it would take a major disaster to drag him/her off the Golf Course or away from the dinner guests.

Not 'joining the dots' seems to be the biggest problem. Looking at symptoms in isolation without looking at the history, making judgements about treatment, without reviewing the notes and tests, that some lab technician has worked through the night, to deliver in time for the operation to be scheduled, or not? Not bothering to see the patient prior to treatment, and failing to provide sufficient information for patients to provide informed consent, due to the unbridled hubris that many display in their protocols and procedures. It is this lack of a continuous care pathway that leads to the sort of disaster that has befallen heart patients at the Nottingham University Hospitals NHS Trust, who failed their patients due to lack of diligence, in ensuring that information about serial episodes of endocarditus was not passed on to others, which in turn allowed lives to be lost without need.

It is far from the first time that this Trust, which is a major Teaching Hospital with intake of 500 F1's per year, has made the headlines. It is in fact rarely out of them, as my friends at National Death Service will attest. This is just in one week! Joining it all together, so that bewildered patients actually get to see a Doctor more than once, during their Hospital stay would be a first step. Actually reading test reports prior to giving dangerous general anaesthetics to people without first knowing, if that act alone might kill them might be the next. Acting on the results of tests, with knowledge of the patient history, is the foundation of treatment. It is not something you should leave to some half baked F2, at midnight on a Friday, whom you have conversed with on your mobile, and directed them to list a trauma patient,  for operation, without seeing them, reading the notes, reviewing the tests and discussing informed consent. Yet it happened. And lives were irretrievably changed, and one almost lost.

Was there any contrition, any meaningful attempt at redress or even candour. Was there even any honesty in providing a prognosis for the future or information of any improvement intervention. Was there b******s. The attitude seems to be, that one should be grateful for having one's life threatened, when you entered their halls, without a life threatening injury; be grateful for surviving. Such compassion. Such empathy!

And there was Peter Homa, standing in front of his Gulag, apologising profusely for the death of the innocents who consigned themselves, to his and others care at his Trent Heart Unit. Only he doesn't care and he never will. Otherwise he would resign, and let someone else take the helm of this graveyard of unnecessary deaths.

So far as the NHS is concerned, it is getting worse as the statistics for Complaints attest. And the bulk of most harms are down to errors. And errors occur most of all when the simple stuff goes wrong. Not the heroic interventions, the open heart surgery, because it was not that, that killed the patients. It was a simple bacteria, that could have been guarded against by protocol. But only if the information had been pieced together. The evidence chain is important, but it is not being given the emphasis needed in today's NHS. Everyone is so busy filling in the screen, the report, the check sheet, that they then fail to read, or take action about. The Doctors can all howl as much as they like, but they are too callow and spineless to do anything about it. They are usually too busy working out the superannuation, and the date of their retirement.

Panorama Highlights Drug Danger to Diabetics

The controversy over Avandia continues to rumble on, and the BBC have at last picked up, that it can cause heart failure in patients, despite the fact that it's makers continue to defend its use. John Briffa, as you see, has warned about this before. But as usual, the machinery of control in the UK, the Medicines and Healthcare Regulatory Agency is once more on a 'go slow' as regards it's withdrawal. Meanwhile more Diabetics may die or be harmed by it's use and Diabetes UK sits on it's hands (Some surprise).

The sad story of Avandia started in 1999 and it was approved for EC use in 2000. It belongs to a group of drugs in the usual 'me too' ranges marketed by 'Big Pharma', called rosiglitazones. They are thiazolidinediones or TZD's (a lot quicker to say, so let's do that). TZD's are PPAR-gamma angonists, which simply put, increase  fat cell generation, as means of increasing glucose disposal. Pause a moment there, because are we not always told, that glucose, is not responsible for fat, but that fat is? So the excess of glucose, probably borne of the excess carbohydrates, you are told to consume as a Diabetic, is being metabolised, more rapidly by gist of this medication, and the mechanism it uses to achieve this is to make you fat! And this is to lower the risks associated with being Diabetic?

At this point I and my few readers may wish to lie down in a darkened room and ponder the logic of such a protocol. So I did and I still cannot see the sense in such a stupid idea, but 'Big Pharma' seems incapable of  going beyond treating symptoms, with measures that bring about others, usually to the detriment of the poor souls who consume the drug. Well, as far back as 2004 there have been rumblings about the drug, with calls for the US FDA to ban it, and 'black label' warnings have been applied to the packaging, warning of the possibility of fluid retention (oedema) which in turn can cause heart problems, but an outright ban has not been invoked
 
The NEJM of June 14th 2007 (New England Journal of Medicine) highlighted the fact that Avandia was associated with a high risk of MI, which was some time ago but as usual little to nothing was done and millions of prescriptions continue to be filled, both in the US and Europe including the UK. The ACCORD Trial was halted due to safety concerns over this, and similar drugs and a number of clinicians are at last raising serious doubts about the validity of all drugs trials, due to the incestuous nature of the (often) authors links with the drugs industry, the grants paid, structure of trials and the withholding of essential data to enable proper independent peer reviews. Well, no shit Sherlock! An increase of 43% of heart attacks, in people that took Avandia for 24 weeks seems pretty conclusive to me!

I also find it unprincipled and alarming, that in most trials, the only way that the full data can be accessed is by paying for for it! The BMJ has a lot to answer for in this by having a pay wall between it and most data other than the (often) 'piss poor' abstract. This is often manipulated to give a 'slant', that is not borne out by the data in the full document. Most if not all trials are in fact paid for directly or indirectly by the drug companies who have vested interests in specific outcomes, and adverse results are often 'buried'. Some principled Doctors and Scientists have condemned this. Perhaps tonight's Panorama programme will delve more deeply into this aspect of 'Big Pharma's' persona. I'm not holding my breath however.

Freedom (well of a sort) Maybe

She cupped her hands, lifted them high, and said "it's time to fly free!". I told her she was a sarcastic bitch, but I knew from the smile, she was just joking. And so we parted. It was the end of an era; an episode in my life that had been perhaps the hardest I had to endure. But she had helped me come to terms with a life less ordinary, that has taxed my identity, my very being at times.

She came to be, that very significant 'other' in my life, someone I became dependent on to help me find a path through the swamp of misery and self loathing I waded through. Someone who became my emotional crutch, my guide, mentor, teacher and so much more. She was all that I did not believe therapy was all about. I have always been a sceptic, a doubter, but this woman treated me with respect, with kindness and did not hector, condescend or in any way act like that I had assumed a therapist would.

She gave me permission at first, to be this incoherent wreck who almost lost the last thing left in his life, and then went about destroying himself in blind rage at the iniquity of it all, and in sorrow for all my failings, as a father, husband, son, and much more. No one had ever done that before, especially for me. I was the serpent, the destroyer of lives. I was not worthy, so I set about proving just how pointless, it all had been, and in the process, nearly lost, that which I had sacrificed much of my wealth, my status, my self worth, for.

Over quite a long time, she set about restoring my soul. That essence of life within us all, that lets us get through each day. With kindness and humility, she teased out, all the horrors, in the Stygian corners that harboured my bleak outlook, were laid bare. I came to depend on those hours; one a week. Sometimes with tears, often with black humour, and eventually, some laughter. She fortified my well being sufficient to face each day. I relapsed many times, but as time went by she tasked me with visits to my worst fears, the place, the time, the events that had shaped my life, and had brought me to her in terror and misery.

I think I owe her my life, and yes, it did get that bad. I had experienced much stress in life, and trauma, as have we all. But I had no idea of what Post Traumatic Stress was about, except that battle scarred soldiers sometimes suffered from it. I really had no idea that I could get it. But I did. It's a dark and terrible place to be. Those who visit it's halls are always left with scars, often worse one's than those that brought them down in the first place. She taught me to honour the experience, that it was not a weakness, merely a symptom of strength that had been stretched beyond it's limits.

Then, she said one day, not too long ago, that we had to part; my time was over. It was her job to impose her own redundancy upon our relationship. I viewed this with some trepidation; fear even. It seemed again that she had trumped the stereotypical view I had held, that this does not happen, that therapy goes on for years. Keeping the fees coming, the subject held to dependence, always seeking new areas of one's psyche to explore, was my cynical take. Well, I had been wrong, and now it was a bit scary to be alone again, responsible for negotiating my own way across the swamp, without a guide!

I kept putting it off, saying I was not ready, that I still had issues we needed to address, but she pressed me, hard. Implying if I did not do it, she would have to. All of course, in the nicest possible way. I have a backstop, an escape route, if all goes wrong. I can ring her for help, talk again in a few months time. In some ways our relationship had changed, with me preempting some of her strategies, even teaching her a few things about my knowledge of the side effects of drugs. I even think she humoured me sometimes to cajole me into taking the reins, not being lead.

It has been a journey. Some of it even a saga related. But. it's over, at least for now and she has my gratitude, my thanks, for leading me into a slightly less dark tomorrow. I hope to be able to walk again without that crutch. I wish I could tell her name, but that would betray all the tenets she lives by. But thank you, you know who you are, and hopefully now, I know who I am too..