This was the stark headline on the BBC News yesterday.  It has been claimed by the National Diabetes Audit for England that huge numbers of patients with diabetes are not receiving the nine mandatory tests that everyone with diabetes should receive annually.
The tests are :

• Blood glucose level (HbA1C)
• Blood pressure
• Serum cholesterol
• Eye screening
• Leg and foot check
• Kidney function
• Weight
• Smoking check
• Care planning

It is not as if any of these tests are new.  They have been enshrined in every diabetes guideline and target since at least 1995.  These include (to name a few):

• What Diabetes Care to Expect
• National Service Framework
• GMS QOF
• Global Guideline for Diabetes
• NICE Guideline for Diabetes
• SIGN Guideline for Diabetes

Amongst other things it is claimed that less than 10% of patients are offered all the tests.  As over 90% of GP’s claim the maximum number of QOF points it is clear that many GP’s are claiming for tests, the results of which they are either not performing or, possibly, recording.

Diabetes UK claim that “this is one of the few problems facing the government that does not require more investment”.

The bottom line is that many patients are suffering from major complications that they do not need to suffer from because blindness, amputation, renal transplants, stroke and myocardial infarction are largely preventable with early detection and management.

The group comprised what appear to be almost all the great and the good from the world of Diabetes in the UK, and so what they say should be worthy of attention. It is.

They have pronounced on various contentious issues and appear in every case to have got it right.

For instance, they do not rule out point-of-care testing providing the users have adequate training and the quality control is adequate.

They also detail the situations where HbA1C should not be used for diagnosis.  These mainly reflect the point that HbA1C effectively gives an average blood glucose estimation for the previous 2-3 months.  Hence in diabetes of acute onset, for instance in children, HbA1C should not be used because it may remain within normal limits for some weeks after the onset of symptoms until the new higher levels of blood glucose glycosylate hæmoglobin at a new higher rate.

They even offer simple guidance on what to do when the test is within normal limits using the relatively new term of “high risk of diabetes” which was formally known as Impaired Glucose Tolerance or Pre-Diabetes.

This guidance is so important that we make no excuse for publishing the full summary, which can be found in the Resources section of our website.

The guidance has been published in many places, one of these being the magazine Practical Diabetes.   Further on in the magazine can be found what one hopes will be the last stand of the Luddites.  They claim that HbA1C diagnosis has a high misclassification rate of nearly 50%.  This sounds alarming until it is realised that they have selected a group for their research that is specifically excluded by the consensus group from HbA1C diagnosis; namely “patients at high risk of diabetes who are acutely ill”.  They used as their sample patients with possible acute coronary syndrome; a group noted for their tendency to high blood glucose levels and where the HbA1C has not yet had time to change.

This paper should be ignored.

Find out more on our Diabetes Management distance learning course, which is always up to date with the very latest developments in the field.

It is interesting to look at insulin a bit more closely.  Human basal insulins have been available since about 1980 and currently cost about 1.27p per unit of insulin.  Analogue insulins have been available since the late 1990′s and currently cost an average of 2.25p per unit of insulin although there is quite a big difference between the shorter acting analogue cost (1.9p per unit) and the longer acting analogue cost (2.8p per unit).

Bolus analogue insulins are more convenient for the patient because their rapid onset of action means they can be taken immediately with, during or even just after eating rather than 20 to 30 minutes beforehand and there may also be a reduced hypo risk if snacks are not eaten between meals but in some a soluble may still be acceptable.

So the BIG question is:  Are basal analogue insulins twice as effective as isophane insulins?

NICE says “No” (they suggest tight restrictions of those who need analogue insulins).

Popular Medical Opinion says “Yes” (over 85% of the annual spend on insulin is on analogue insulins).

On a cost basis this translates to nearly four times as many patients being prescribed basal analogue as opposed to human basal insulins.

So who is right?

NICE is government financed.  One would therefore expect them to have cost in mind when making recommendations.  However, in this case, their recommendations are backed by firm evidence. These show that:

On the basis of these findings, NICE recommend that basal analogues may be considered (rather than isophane) in patients:

1. Who require assistance with injecting insulin
2. Who cannot use the device needed to inject isophane
3. Whose lifestyle is significantly restricted by recurring hypos
4. Who would otherwise need twice daily basal insulin injections in combination with oral antidiabetic drugs

The first two recommendations are a little odd.  The devices used to inject basal analogue insulins are generally similar to those used for isophane although the NovoNordisk FlexPen is not available for isophane (one wonders why) so 1] and 2] are difficult to interpret.

The Bottom Line

It will be difficult for practitioners to resist pressure from on high to change from basal analogue to isophane insulins for routine use.  So far the manufacturers of the newer drugs have failed to demonstrate any major advantage of the new drugs.  There is a lot of pressure from them for us to regard isophane as old-fashioned.  Isophane has been around for a while but it is still an excellent insulin.

We can look at Risk Charts.

We can contemplate Numbers Needed to Treat.

We may have treated ten people after a myocardial infarction with low dose aspirin and been told that we have prevented one major event in one person.  But which person?

We may have lowered blood pressure in ten people and reduced the chance of them having a stroke from 15% to 5% but may be the ten people were in the other 85%.

So it is gratifying to read a headline such as appeared in a daily paper recently:

“Deaths from heart attack halve in a decade“.

Now that’s impressive.

80,000 heart attacks and 28,576 deaths have been prevented.

Hey – that’s 16 heart attacks and 6 deaths in OUR practice.

Of course, all the dismal jimmies are out there saying that it’s only temporary.  Obesity and diabetes will soon push the figures back up again.

Stuff them and pat yourself on the back (for it’s unlikely that anyone else will) on doing a good job.

Fancy, 6 deaths prevented.  The trouble is, one of them might be Mrs Moana.

The story actually dates back to the mid-nineteenth century when Paul  Langerhans described the groups of cells known as the Islets of Langerhans in the pancreas without realising what their function was.  Oscar Minkowski and Joseph von Mering later found that when experimenting with a dog, if the pancreas was removed the dog developed diabetes but that if the duct was ligated, it did not.

In the popular mind insulin was discovered by two Canadians at the University of Toronto, Frederick Banting and Charles Best but two other people were heavily involved,  the head of Banting’s department, a Scotsman called John McLeod and another scientist Bertram Collip.

Basically, Banting wanted to explore the functions of islet secretions by performing some experiments on dogs.  He was allotted a laboratory by McLeod, who oversaw the experiments.  Banting co-opted Best who was a medical student and, later when things started to move quickly, Collip.

Things developed rapidly after a dog which had had its pancreas removed was kept alive and its blood glucose level low by frequent injections of islet extract.  Collip was able to purify islet extract.  McLeod suggested the name “insulin” from the Latin word for island.

The first human with diabetes was given insulin in January 1922 and the patient, Leonard Thompson made a dramatic recovery.  Within nine months, the substance had received a product licence (eat your hearts out pharmaceutical companies !) and was manufactured by Eli Lilly who are, to this day, one of the main players in insulin manufacture.

The first cracks in the team came in 1923 when McLeod and Banting were jointly awarded the Nobel Prize in Physiology or Medicine.  Banting was furious and immediately donated half of his prize to Best.  McLeod countered by giving half his prize to Collip.

Within a year, Eli Lilly were producing large quantities of insulin while the European rights had been granted to Nordisk, one of whose partners was Hans Christian Hagedorn who, in 1946, discovered Isophane or Neutral Protamine Hagedorn (NPH)insulin.

For the first 60 years, all insulin was extracted from cow and, later, pigs’ pancreas.  Until the late forties when the longer acting isophane insulin was produced only soluble insulin was available.  This had to be given at least three times a day using syringes and needles that were sterilised between each injection.  Plainly people treated at this time had sub-optimal glycaemic control and yet many survived for many years, indeed some of the earliest people treated with insulin have only just died, having received insulin for as much as 80 years.

For many years all those treated with insulin had Type 1 Diabetes.  The first suggestions of insulin resistance were made by Professor William Falta in 1931 and developed by Sir Harold Himsworth in 1936.  Although Type 2 Diabetes was known and treated with sulphonylureas, metformin and, occasionally, insulin, insulin resistance was almost forgotton until G M Reaven’s ground-breaking Banting Lecture in 1988.  He proposed the existence of also-called “Syndrome X” which later became known as “metabolic syndrome”.  These terms have now almost been abandoned with Impaired Glucose Tolerance (or Pre-Diabetes) and Type 2 Diabetes being the preferred names.

Meanwhile things was starting to progress in insulin.  Until about 1970 soluble and isophane bovine or pork insulin were available in strengths of 20, 40 and 80 units/ml.   The potential for confusion was solved with a wholesale switch to 100 unit/ml insulin.

The pathway to synthetic insulins was laid by Frederick Sanger and Dorothy Hodgkin in the 1950′s and 1960′s; both of whom won Nobel Prizes for their work.  This work led to the synthesizing of insulins by genetically modifying yeast or bacteria to give the so-called “human insulins”.  The latest development came at the end of the century when the first “analogue” insulins became available.  These are produced by recombinant DNA technology (or molecular cloning).

At present there are 2,200,000 people in the UK with diabetes of which about 300,000 have Type 1 Diabetes.  So probably upwards of 600,000 people are treated with insulin. Things have come a long way since Leonard Thompson.

Learning links:
Diabetes Mangement distance learning course
Insulin Conversion study day

“On your left – Mum denied new cancer cure drug”

“On your right – New drug causes serious side effects”

Plainly, there has to be a balance between pharmaceutical advances and adverse side effects.

At present, it is enormously expensive both in time and money to bring a new drug to the market place.  Companies look at thousands of compounds for possible beneficial effects and test many on animals before even contemplating human treatment.  If a drug passes all these tests, it then enters clinical trials which are divided into four “Phases”.

In Phase 1 trials, a drug is tested on healthy volunteers to check for serious side effects.

Phase 2 involves testing the drug on volunteers with the disease at which the drug is targeted.

Phase 3 is the one which causes the problems because it involves testing the drug on large numbers of patients.

If a drug passes all the phases it may then be given a licence and marketed by the company.

Phase 4 relies on those prescribing a drug to report back on any possible harmful effects of the drug.

Drugs drop out of the trials at all stages and the whole procedure takes up to and over ten years and costs several hundred million pounds.

David Cameron has announced plans to streamline this process by, for instance, allowing seriously ill patients to receive new drugs before they have received a product licence – a sort of Phase 3.5. By doing this, he hopes to attract back research to this country from whence it has fled due to red tape and potential scientists being denied entry to this country by the stricter immigration laws.

Commenting on the red tape covering trials in this country, this reporter says that many drugs are now trialled in India.  Perhaps he forgot criticising that country a few weeks ago for being, shall we say, rather lax in its ethics about administering new drugs to paid volunteers.

Right or wrong?

Medical research is not in a good state.  Researchers ask questions not necessarily because they are important but because someone is prepared to pay for the research.  For example, you won’t find anyone willing to pay for research to find the ideal dose of aspirin to prevent further myocardial infarctions, yet that was not the case with simvastatin in 1994.  Reason:  Aspirin costs 75p per month (small profit) and Statin £20 per month (large profit).

On the face of it, it seems a great idea to streamline the development of new drugs and yet there are still those niggles which ask how, after years of testing a new drug, it can be withdrawn less than a month after launch due to serious liver side effects.

If I was a government wanting to inject £180,000,000 into drug research, I would bring together a panel of experts, lock them in a room after telling them that they could not come out until they had listed the ten most important medical research questions that need answering.  Only research which addressed one of these questions would receive funding.

Simple, hey?

So, WAKE UP all you podiatrists and women’s health experts.  It’s your turn now to be in the firing line as the conditions of peripheral vascular disease and osteoporosis have been included for the first time after, one would assume, a great deal of lobbying on behalf of the specialities.

The peripheral vascular disease criteria include, as you would expect, the issues of anti-platelet therapy, blood pressure and aspirin.

The osteoporosis criteria look at the use of bone-sparing agents in the under and over 75′s.

In addition to these criteria, the A & E people have obviously been twisting a few peoples’ arms with 31 extra QOF points to try and stop us filtering off our problems to A & E departments.  Remember the “Please see and treat” days?

A summary of the changes can be found on our website, together with the full listing in our Resources section.

As you would expect, all of our courses conform fully to the latest nGMS QOF criteria.

He claims that there are serious flaws in both the medical profession and the pharmaceutical industry.

He makes veiled criticism of the medical profession for first inventing and then carrying out coronary angioplasty. He comments that, presumably because the operation is so simple and effective, the number benefitting from the procedure has increased twelvefold.

I doubt whether a patient with angina, whose life has been saved and enhanced, would agree that too many of these procedures are carried out.

He then moves on to take on the might of the pharmaceutical industry. He argues against multiple drug prescriptions in general and statins in particular.

First of all let’s look at a few figures:

1. A rise of 1mmol/l of cholesterol increases the risk of a severe cardiovascular event by 72%.
2. A reduction of 1mmol/l of LDL reduces the risk of a severe cardiovascular event by 23%.
3. The life expectancy of a female has risen from 73 to 82 since 1970.
4. A month’s course of simvastatin 20mg daily costs less than £1.
5. A person with Type 2 Diabetes is at high risk of premature death due to hypertension and dyslipidæmia.

Mr le Fanu starts off on the pharmaceutical industry by criticising polypharmacy. The majority of patients who are on half a dozen or more prescriptions daily – a figure which Mr le Fanu finds particularly shocking – are those with Type 2 Diabetes.

These people, who have hyperglycæmia, are at high risk of developing hypertension and dyslipidæmia, from where it is a short journey to cardiovascular disease and premature death. However, if hypertension is managed effectively (which virtually always requires three different medications), if hyperglycæmia is managed (which often requires two different medications) and if dyslipidæmia is managed (which may require more than one medication) then the life expectancy can be increased to normal.

This result is not caused by pharmaceutical companies ramming medications down patients’ throats. It has been proven time and again by repeated research projects to be a highly effective way of managing this life-long disease.

The onslaught on statins is particularly unfortunate. He mentions (unspecified) side effects of statins despite the British Heart Foundation commenting that statins are among the safest of drugs with a large amount of research evidence supporting their use.  The only severe side effect is rhabdomyolysis. The incidence of this is about 1 in 100,000 patients. Hardly common. The remainder are reversible and probably dose related. He does not mention the beneficial effect on reducing cholesterol by a figure of approximately 25%. That’s a big saving of lives.

So where’s the problem?

It is no accident that the life expectancy in the United Kingdom has risen by 10 years in the last 45 years. Would the many people who are living 10 years longer as a result of the developments within the medical and pharmaceutical profession agree with Mr le Fanu’s criticism? Perhaps not.

One final thought. I wonder if Mr le Fanu is any relation of Sheridan le Fanu, one of the most famous writer of ghost stories in the 19th century.

Find out more about some of these issues on our Diabetes Management and Cardiovascular Disease Management distance learning courses.

The reason I ask this question is all to do with diabetes and HbA1C.  In fact the subject is strangely reminiscent of a similar situation about fifteen years ago with blood glucose levels.

For several years, some professionals have wondered whether it would be possible to make a diagnosis of diabetes on the basis of an HbA1C estimation.  In the case of Type 1 Diabetes, this is plainly not possible, for the onset of this condition is often sudden and dramatic so that the HbA1C  level has not had chance to change to its new level.

But in the case of Type 2 Diabetes, which has a slow and insidious onset, then plainly this should be possible.

The World Health Organisation convened a consultation with experts in every field remotely connected with the management of diabetes and concluded that “HbA1C  can be used as a diagnostic test for diabetes, provided that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement.  An HbA1C  of 6.5% (by the way, what’s happened to the mmol/mol we’re supposed to be using?) is recommended as the cut point for diagnosing diabetes.  A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests.  The expert group concluded that there is currently insufficient evidence to make any formal recommendation on the interpretation of HbA1C  levels below 6.5%.”

So that’s alright then.  That’s what we’ll do in future.

No it isn’t, actually.  Well, not in the UK anyway where the recommendations have not been adopted without some quibbles.  One of the dottier is that it may lead to more people being diagnosed with diabetes.

Would you rather be told that you have got diabetes and have your risk factors for cardiovascular disease carefully managed; or not know that you have diabetes and continue to rot away your arteries?  I know what my answer would be.

What possible other explanation is there of an HbA1C  over 6.5% other than that the patient has got diabetes ?

If worldwide organisations are going to spend a lot of time and money in such an important subject and individual countries are just going to plough their own idiosyncratic furrow, what on earth is the point of continuing with such an organisation?

Fifteen or so years ago, exactly the same situation arose.  The World Health Organisation announced new diagnostic levels for the diagnosis of diabetes based on random and fasting levels of blood glucose, plus glucose tolerance tests were indicated.  Here at the Training Centre, we spent many cumulative hours explaining to puzzled students that, although the new levels had been announced by the World Health Organisation, they had not been adopted in the United Kingdom.

Find out more on our Diabetes Management distance learning course.

Today we take randomised trials of new treatments for granted but it was not always so.  Until the early fifties, researchers tended to select patients for trials of new drugs that they thought would benefit from them.  Meier suggested that patients should be chosen randomly and compared with another random group which did not receive the treatment.

Many doctors were horrified and claimed that they knew that a new treatment worked but Meier responded, “Well, not really.”

Meier also, along with Edward Kaplan, produced new curves and equations to estimate survival rates of medical treatments.  These enabled survival rates to be calculated at every stage of a trial.  These tools are used in virtually every study in progress today.  They are also the tool by which patients can be informed of the likely success of a possible treatment 5, 10 or even 15 years ahead.

As always it took a long time for Meier’s ideas to become indispensible to medical research.   In fact it needed the American Nurses Trial published in the nineties, which committed a generation of women to take HRT in the false hope that it would prevent them developing cardiovascular disease, to enshrine Meier’s work completely.  When randomised trials were eventually published in the early 2000’s, it was shown that the effect of HRT was at least neutral with regard to cardiovascular disease.  This put the final nail in the coffin of non-randomised trials, 50 years after Meier had first proposed his alternative.

Meier deserves to be remembered as such pioneers as Pasteur, Curie and Fleming as one of the true greats of medicine.  If you want a final point, look at the way decisions are reached in another field such as economics.  Evidence-based?  What’s that?