DRWF Research Manager Dr Eleanor Kennedy reports from the Diabetes UK Professional Conference in Liverpool.
The Diabetes UK Professional Conference is drawing to a close but Day 3 is still bustling at the conference centre. Yesterday’s rain may have stopped but people’s enthusiasm and commitment have not and the first session of the day, which kicks off at 8.30am, is full of delegates there to hear about diabetic ketoacidosis (DKA). And, on International Women’s Day, it is great to be there to hear Dr Shivani Misra, one of the DRWF’s Clinical Fellowship awardees, give a convincing presentation about the diagnosis and treatment of diabeteic ketoacidosis, an important issue in diabetes care and management.
The so-called Hot Topics session which follows runs through some important issues that are really at the forefront of research at the moment. Professor Cliff Bailey from Aston University in Birmingham continues the discussion on DKA but, this time, in relation SGLT-2 inhibitors. This new and very exciting class of drug which works by facilitating the excretion of sugar (glucose) via the kidneys has, until very recently, only been available for people with type 2 diabetes. It is now, under very defined circumstances, allowed to be prescribed to people with type 1 diabetes, but there are very grave concerns about the increased risk of DKA and this is splitting opinion.
Clinical trial data is helping us to understand better the degree of DKA that is occurring but the issue remains that people with type 1 diabetes who are in these trials are well educated about the risks of DKA and how to measure their ketones and even they appear to be struggling.
Clearly much more work needs to be done to unite the diabetes world and to convince those who remain sceptical about the utility of SGLT-2 inhibitors in people with type 1 diabetes.
Another area covered during the session, this time by Professor Kamlesh Khunti from the University of Leicester, is about the possible advantages of early combination therapy. In patients with type 2 diabetes, it is more common to start them, post-diagnosis, on one drug and then to add incrementally over a number of years, other drugs to improve glucose control and, often, blood pressure.
But what if we added more drugs at an earlier stage? Could this improve outcomes? Professor Khunti argues that this could lead to the earlier achievement of therapeutic goals as well as a potential reduction in the risk of side effects if drugs are added at a lower dose together closer to the point of diagnosis. There could also be an opportunity to combine oral antidiabetic drugs with complementary modes of action which could have the potential to delay disease progression. Importantly, however, there is evidence to suggest that this strategy could actually improve compliance rates.
Compliance rates become increasingly difficult with the more drugs a person is asked to take. Fewer people will take more than one drug, fewer still more than two drugs and so on but, for some reason, the early adoption of a multiple drug regimen appears to have a counterintuitive effect and ensure that more people take their full drug schedule. So are new combination therapies and educational programmes one possible solution to therapeutic inertia? Again, we’ll need more research on this before a definitive answer is available.
The standard of talks and of interaction this year has been terrific and I’ve had the great privilege of being able to listen and to report on so much. But I have kept the best to last. A series of talks that blew the audience away.
You may recall that I said at the end of my blog from Day 1 that I had met Professor Andrew Hattersley and that he had more or less bet me that I wouldn’t attend a session that he was leading late in the afternoon on Day 2. “And he reminds me of a session tomorrow evening that I shouldn’t miss – he’ll be speaking which means that it’ll be good!”
I go. And it is!
The hormone, insulin, is produced naturally as a molecule called preproinsulin which is biologically inactive. Preproinsulin is converted into proinsulin and then proinsulin is converted into insulin by the removal of a short piece of protein called C-peptide. And it is this simple little protein that was the subject of a series of talks that keeps me and hundreds of people in a packed to the brim and standing-room-only lecture theatre engrossed.
Crudely speaking, it is the loss of C-peptide that is the characteristic of people with type 1 diabetes. As endogenous levels of insulin fall, intuitively C-peptide levels will also fall because no proinsulin is being made as the beta cells that make it continue to be attacked by an immune system that has gone rogue. However, measuring C-peptide levels was, at least historically, difficult to do and relatively expensive so it was not often done. But times have changed and they can now be almost routinely measured. So how do we know, without measuring the definitive marker of type 1 diabetes, that we’re actually diagnosing cases of type 1 diabetes correctly.
The short answer is we don’t!
In a type 1 diabetes clinic in Edinburgh, the consultant, Professor Mark Strachan, decided to measure the C-peptide levels in his patients being treated with insulin for type 1 diabetes. Of a clinic of 953 people, he tested 757 and found that 103, or more than 13%, actually had detectable C-peptide levels. Within this cohort, he found people who had monogenic diabetes who do not need to be in insulin therapy and he detected rare and unusual forms of the condition including a mitochondrial genetic disorder that is characterised by diabetes and deafness.
Which takes me back to my assertation yesterday that neither type 1 nor type 2 diabetes is a single condition. This research shows so elegantly and so simply that what we thought was a simple distinction is, at least in part, incorrect. There are people with type 1 diabetes who are still producing a lot of C-peptide and those who are being misdiagnosed because of a genetic mutation.
I hope that, as I wave goodbye to Liverpool and head home, next year’s conference will be dominated by new research on the clustering of type 1 and type 2 diabetes. This test could help researchers to start identifying who has detectable levels of C-peptide and that in itself, could lead to a seismic shift in the way we diagnose and treat what today we call type 1 diabetes and type 2 diabetes.
Personalised medicine isn’t on the horizon. It’s coming home to roost!