How will we afford the diabetes epidemic?

The oldest adage in the book “prevention is better is cure” could never have been more apt than now. We didn’t really need reminding, after all the figures are already terrifying but this week’s publication of the SABREstudy does rather highlight the point, there’s a lot of diabetes around and it’s getting worse.

Specifically, the SABRE study has shown that in an urban population of middle aged people followed up for 20 years, by the end of follow up, 15% of the Europeans had developed diabetes, 33% of the Asian Indian population had it and 30% of the African Caribbean subjects had developed it.

The figures for the European subjects are bad enough and very much chime with the ~15% prevalence of inpatient diabetes found by the national diabetes inpatient audit, but for the ethnic minorities they are staggering, and mean that roughly 1:3 of all Asian Indian and African Caribbean patients in many parts of the country may have diabetes. Furthermore, these figures were used to predict that by age 80, the prevalence will be 1 in 2 in these groups, in other words, it will be safer to ask “does my patient not have diabetes?” rather than “might they have it?”

Of course these figure should not be a surprise, we already know that globally, the WHO is predicting ~440M with diabetes by 2030 and that approximately 10% of all NHS budget is now spent on diabetes and diabetes related conditions/complications. Thus, it is well recognised that the current rate of growth is un-sustainable and will bankrupt the NHS if nothing is done. So surely now is the time to focus on diabetes prevention strategies. The Diabetes Prevention Programme and Finish Diabetes Prevention Study (as well as several other smaller/less well publicised studies) established the precedent, it is possible.

Now the challenge is how to convert the theory of diabetes prevention in to practice. Leaving aside the pharmacologic interventions used in some study arms, the principles are simple, identify the higher risk individuals and get them to make modest adjustments in their diet, aim for relatively small weight loss and modest increases in physical exercise. The challenge is to convert these principles in to a pragmatic, practical, achievable strategy on the ground. The sorts of resources employed by the investigators in the DPP and DPS diabetes prevention programmes, if scaled up to a population level, would also, like the costs of diabetes itself, potentially bankrupt the NHS.

The challenge will therefore be to scale up these sorts of interventions on an affordable footing. The results of the Norfolk Diabetes Prevention Study and others employing less intensive, more “real-world” interventions to affect diabetes prevention should provide clearer ideas on how best to achieve diabetes prevention on an affordable basis. In the meantime, studies such as SABRE only serve to remind us of the extreme importance of this particular public health challenge.

A pregnant pause in diabetes treatment...

Diagnosing gestational diabetes is easy, isn't it? - any degree of impaired glucose intolerance in diabetes. Well maybe, but how to define any degree of glucose intolerance in pregnancy seems to be a lot more difficult than you'd have thought.

For the clinician at the coal face in hospitals around the UK (and indeed around the world) a major factor underlying this difficulty is the vast range of discordant recommendations. In the UK, we have NICE advising us to diagnose GDM on WHO criteria, i.e. a fasting blood glucose of 7.0 and a 2 hr 75g OGTT value of 7.8. Until recently the ADA was recommending a 75 g OGTT with fasting, 1 hour and 2 hour cut offs of 5.3, 10.0 and 8.6, with 2 or more readings elevated for a diagnosis. More recently, following the publication of the HAPO study, the IADPSG have recommended cut offs of 5.1, 10.0 and 8.5 (fasting, 1hour and 2 hour respectively) on a 75 g OGTT, with only 1 level needing to be elevated for a diagnosis.

Not only is there therefore a wide range of different diagnostic criteria available, but there is an elephant in the room: adopting the IADPSG criteria will more than double the prevalence of GDM in most ante natal clinics at a stroke. When many antenatal services are already struggling to meet demand, this situation will be untenable in the short to medium term until further resources are made available.

It is therefore not surprising that some centres are sticking to old sets of diagnostic criteria and others are modifying the newer diagnostic criteria in an attempt to compromise by simultaneously adopting new criteria and managing the numbers at the same time. Anecdotally, some centres, for example are considering adopting IADPSG but stratifying cases so that 2 elevated readings would trigger entry to the antenatal diabetes clinic, 1 elevated reading would trigger mid-wife or standard antenatal clinic-led, diet-based management with potential later transfer to the antenatal diabetes clinic if acceptable glycaemic control was not being achieve.

In summary, the field is wide open and practice at present is highly variable, we desperately need authoritative practical guidance, in the meantime, the pregnant pause continues...

Dr Jeremy Turner has updated the GDM guidance on Diabetesbible. Click here to read. 

Glimmer of hope for obese type 2 patients

Back in the days of UKPDS it was firmly established that insulin-initiation in patients with type 2 diabetes leads, on average, to a weight gain of around 7Kg in the first 12 months after initiation.

Patients and their doctors do not like this. The patients feel disempowered as they watch their weight remorselessly climb and their doctors have a sneaking suspicion that they are doing little more than ‘fuelling the fire’ of insulin resistance.

Although the latter concern has a strong theoretical basis, we should remember that even with the observed weight gain, there is strong evidence that intensively insulin-treating T2DM leads to better outcomes than not doing so.

Nevertheless, the weight issue remains and is only becoming more of a problem as the background average BMI in the population increases. In 2007, a new class of T2DM drug was launched – the GLP1 agonists and indeed initial experience has been encouraging with the ABCD UK national audit of exenatide reporting a mean 0.7% HbA1c reduction and a mean 5.9Kg weight loss in the first six months with broadly acceptable side effect and safety profile (to date).

Of course we do not yet know if these results, which after all are only surrogate end points, will translate ultimately in to reduced mortality and morbidity but for now the portents are good. Thus, for the first time in T2DM there has been a meaningful alternative to insulin inititiation, and more importantly one which offers realistic hope of weight loss, when the old metformin/sulphonylurea combination is no longer cutting the mustard.

However, until very recently, a large and important group or patients has been excluded from the party – those whose HbA1c is so way out of range or whose beta cell exhaustion so advanced (or both) that insulin is mandated. Of course some have already been (perhaps quite rightly) combining insulin with GLP1 agonsists “off license” and again the ABCD UK national audit gives us a useful snap shot of this situation, showing that across the UK already ~30% of prescriptions for exenatide were written in combination with insulin.

However, it will come as a relief that this practice has finally been officially sanctioned. Many of you will have received a communication from Lilly/Amylin in the last couple of weeks that twice daily exenatide is now licensed in Europe for co-prescription with any basal insulin (and metformin plus/minus pioglitazone). Although the study that led to this license extension was performed with insulin glargine, the EMA’s decision pragmatically and sensibly does not restrict the approval to lantus.

Encouragingly, there was no more hypoglycaemia in the exenatide/glargine arm of the study than in the glargine/placebo arm.

Although it will remain essential to monitor patient's responses in terms of weight and HbA1c improvement, to stop this costly combination where there is little/no benefit and to remain philosophical about its use while there is an absence of hard evidence of long term benefit, this step offers one more bit of good news to patients.

I think the next challenge for this interesting area of pharmacotherapy is to see what guidelines NICE lays down around the GLP1-insulin combination in its next iteration of CG66-CG87-type 2 diabetes clinical guidance.

Avoid the mistakes of the past with new drugs

The recent history of new drugs for type 2 diabetes teaches us to approach this area with caution.

Rosiglitazone has been withdrawn in the wake of the Nissen New England Journal meta analysis, before that, Troglitazone was withdrawn after several fatal episodes of hepatic failure. More recently, Pioglitazone has had a large number of cautions and contraindications attached to it, the most recent being a possible increase in the risk of bladder cancer.

Admittedly all three of these examples belong to the same class of drug but these are still salutary lessons that should serve to remind us to treat novel hypoglycaemics with caution. The UKPDS data is now relatively old and included a population of patients who were slimmer, older, smoked more and took less statins at baseline than newly diagnosed type 2 diabetes patients typically are nowadays.

Notwithstanding these limitations, this is still the most authoritative and largest RCT of glycaemic and blood pressure control in newly diagnosed T2DM and one of the largest RCTs in T2DM period. Thus, one could argue that we would still be well advised to pay heed to its results. These clearly and unequivocally showed that good glycaemic control with insulin or metformin or sulphonylureas or combinations of the above and good blood pressure control are highly effective at reducing the incidence of micro and macro vascular complications and moreover, these benefits are long lasting even after cessation of intensive intervention in the so called “legacy effect”.

In contrast, newer agents have a near absolute absence of evidence of long term efficacy, have yet to have their long term safety demonstrated and are massively expensive in comparison with metformin, gliclazide and human insulin. So, how should we approach drugs such as the GLP1 agonists? On one hand, they are effective at reducing HbA1c and have the near miraculous benefit of making weight literally fall off of many patients who take them. On the other hand they are costly, there is no data showing that their BMI and HbA1c benefits translate into a reduced incidence of complications or better still, reduced mortality, and their long term safety is far from proven.

So, what test should we apply when trying to balance these considerations? I would like to make a near heretical suggestion in this day and age of evidence-based, cost effectiveness modelling, and guideline-driven medicine; I would like to suggest that we use good old fashioned clinical judgement and a smattering of common sense! The HbA1c reductions are sizeable for many, the weight benefits are of a magnitude that are likely to yield significant cardiovascular benefits if maintained.

In ‘non-responders’ they should clearly not be continued, but their cautious use in a restricted population of responding patients combined with a high degree of clinical vigilance would therefore seem like a reasonable approach while we await more definitive long term outcome and safety data. I think the mistake that we must not make yet again is the wholesale, unthinking, blanket adoption of yet another new class of hypoglycaemic drug while there is still an absence of proof that we are really giving our patients any meaningful long-term benefit.

Avoiding the language of control with diabetes

"Your diabetes control is really not terribly good and if you carry on like this year after year your risk of getting long term complications from your diabetes is really quite high."
It's a line I have to say all too frequently - though as gently as possible - to patients.
But it strikes me that 'control' is rather an emotive word. I wonder what the patient hears when we say this sort of thing? Perhaps something along the lines of "I'm finding it very difficult to control you and you are a very naughty patient," or "Just as your school teachers of yesteryear said, you aren't doing very well and must try harder."
Maybe some do hear the message as it was intended. However, I remain concerned that 'control' is a bad choice of word for describing the end result of the daily wrestle with one's blood sugars.
There are subtle insinuations that arise from the word. Perhaps 'control' implies that one factor or one person is dominant over another (the doctor over the patient maybe?). Perhaps it implies something regimented, predictable or inflexible, precisely the attributes that one wouldn't normally associate with a biological variable such as blood glucose levels. Perhaps, worst of all, there are connotations that the diabetes might be controlling the patient - a sadly common occurrence.
The 'C' word is not a desperately good word for describing how optimal or otherwise a patient's glycaemia is. Indeed I go through phases of trying not to use it. I replace it with euphemisms such as the aforementioned 'glycaemia', synonyms such as 'regulation' or the rather obvious and unimaginative 'HbA1c'.
However, whenever I do so, my clinic letters take on a stilted, almost constipated air which must seem very strange to the colleague reading them and thus inevitably, unavoidably, I eventually revert back to 'control'.
In the 21st century, in an era of patient empowerment, can we not find a better word to use when discussing the central issue of long term glycaemic regulation with our patients - a word that carries less hidden emotional power, a word that helps rather than hinders our patients?
Answers on a postcard...

Hello, hello, hello, what’s going on here then...

Do I work for the NHS or the DVLA? This is what I found myself wondering about in my last clinic.

It’s rare in medicine that your duty to act as the patient’s advocate is not the over-riding factor in all clinical decision-making. However, if you are fortunate enough to be a diabetologist, then several times a month you will find yourself in the professionally invidious position of doing the DVLA’s bidding, potentially not putting the patient’s concerns centre stage.

Allow me to furnish you with a hypothetical scenario. A 42-year-old patient with a 20 year history of diabetes consults you for their routine annual review and during the appointment also requests that you complete a medical questionnaire for the DVLA. They have the form with them and plonk it in front of you. You are working your way through the questions fairly well until you get to the one that asks if you have inspected a written record of their recent blood glucose monitoring results.

You are happy that day-to-day glycaemic control is not a major problem for this patient, their HbA1c is 59 mmol/mol, the hospital notes bear witness that they have never been seen in A&E with a major hypo - nor trauma from a road traffic collision caused by hypoglycaemia for that matter. They verbally report no major hypos and good hypoglycaemic awareness and your clinical instincts tell you that you have no reason to disbelieve this account of things.

You have previously scrutinised their glucometer and recorded in the notes “glucometer readings mainly single figures/low teens”. However, they do not have either glucometer or glucose monitoring diary with them today. You would not be making an issue of this minor point were it not for the DVLA form, after all, have you never, not even once, arrived at work without your hospital ID badge? We are all human.

But now the pressure’s on, the patient’s driving license is about to expire, they need it for their livelihood, they have to get the form back to the DVLA in the next three days or the license expires. Do you just tick the box saying you’ve inspected the glucose monitoring diary? No, better not do that, what if that one in a million chance comes to fruition and they have a huge hypo on the way home and plough in to a crocodile of school children on a zebra crossing?

OK, plan B, politely explain to the patient that it will not be possible to complete the form today even though your professional instincts are telling you that to do so would be quite OK? You explain, the remonstration starts, the pleading, the imperative to keep driving with which you so completely empathise. Now, from being kind, sympathetic, benevolent, you are cast as cruel, heartless and callous.

Not only has this consultation gone badly wrong, but the entire therapeutic relationship has been seriously injured, perhaps forever by a third party who was never invited to this consultation in the first place. Oh dear, how did it ever come to this? Did you ask to be both policeman and doctor at the same time? I suspect not, I know I certainly didn’t.

For advice on driving and diabetes CLICK HERE.