DRWF Research: How lifestyle and environmental factors could help provide personalised treatments for people living with type 2 diabetes
Published on 28 April 2021
Read Day Four of DRWF Research Manager Dr Eleanor Kennedy’s blog reports from the Diabetes UK Professional Conference and another packed half-day of sessions and symposia.
Following on from my musings last night about the shadow of Covid-19 hanging over everything at the moment, it is perhaps not surprising that one of the very well attended sessions of this fourth day is entitled Re-shaping diabetes services post Covid-19.
Professor Johnathan Valabhji, National Clinical Director for Obesity and Diabetes at NHS England and the chairman for the session, opens proceedings for the day: “The last 12 months have been like no other year in our lives in terms of Covid-19 and its impact on all of our lives and society and, in particular, its impact on people with diabetes.”
To their credit, healthcare services provided around the UK regrouped quickly in the face of the emerging crisis, moving many appointments online - but what will be the lasting impact of this on the services offered going forward?
Impact of Covid-19 on services for people with type 2 diabetes
Dr Matthew Carr kicked off the session with a talk about the indirect effects of the Covid-19 pandemic on type 2 diabetes diagnosis and monitoring across the UK. Using the Clinical Practice Research Datalink (CPRD), his team collected anonymised patient data from GP practises which informed them about, for example, the rates of diagnosis of type 2 diabetes.
During 2019, this was relatively steady at 35-40 per 100,000 person-months. However, in March 2020 at the start of the first lockdown, this plummeted by 70% compared to the previous year. This drop was mirrored by a fall in the number of new metformin prescriptions. Using extrapolation estimates, the researchers noted that there were approximately 60,000 missed or delayed diagnoses across the UK between March and December 2020 leading the speaker to conclude that services will need to manage this backlog whilst ensuring that patients remain engaged with services particularly as the move towards home monitoring and remote consultations becomes the mainstay of care and management going forward.
Enhancing diabetes care
Dr Clare Hambling, a GP, then discussed the shaping of primary care diabetes services post-Covid-19. In her view, the priorities for enhancing diabetes care in a multidisciplinary primary care network include early referral and intensive support for people newly diagnosed with diabetes including attendance at structured education courses, a holistic approach to care addressing the long-term disease burden and with focused care on vulnerable and underserved populations. She concluded with a rallying call to those working in primary care to maintain the momentum and to embed what has worked well and to change what has not, building on the opportunity that reconfiguration of services is offering and will continue to offer.
From there, I switched focus completely to listen to some excellent talks on genomic and precision medicine in diabetes.
This is a complex area but a field that is demonstrating that genetics can be used to capture individual differences in the etiological contributions to the development of type 2 diabetes that can, in turn, be related to clinically relevant outcomes. The translational value of human genetics for rare diseases and for certain forms of cancer has been clear for some time and is now beginning to have some traction for common complex traits like type 2 diabetes. And this, of course, has implications for future therapeutics by highlighting patient stratification that may result in faster trials, better outcomes and risk profiling allowing for rational drug design.
Working towards personalised treatments for people living with type 2 diabetes
The session ends with a talk from Professor Anna Gloyn, a valued member of the DRWF Research Advisory Board for many years, who recently moved from the University of Oxford to take up a position at Stanford University in California.
Professor Gloyn started by thanking the genomics revolution, catalysed back between 2000 and 2003 when a complete human genome reference sequence was published. Technological advancements for sequencing and genotyping at scale subsequently decreased in cost allowing increased access to this material which stimulated the creation of large biobanks and precision medicine sequencing efforts.
One of the most common forms of monogenic diabetes – maturity onset diabetes of the young (MODY) - is the poster boy of such genetics research as it helped to identify a form of non-insulin requiring diabetes that presents in children and young adults typically under the age of 25 years old and that is characterised by an autosomal dominant inheritance.
Researchers have now identified at least six sub-types of this condition. This has, in turn, allowed identification of glucose sensing mutations which require no treatment at all, insulin secretion mutations that require only a low dose sulphonylurea, channel disorders that need to be treated with high dose sulphonylurea and ectopic fat monogenic subtypes of diabetes that need treatment with metformin elegantly demonstrating precision medicine that is already in the clinic.
However, Professor Gloyn recognised that such precision medicine for type 2 diabetes will be a lot more problematic as it is a polygenic condition complicated by environmental factors. However, there are some exciting examples of possible stratification medicine.
For example, fasting C-peptide and antibody status, two clinical markers of functioning pancreatic beta cells, can be used to define a response to GLP-1 receptor agonists, one of the newer classes of drug in the diabetes armamentarium. High levels of fasting C-peptide and a negative antibody status indicate that a patient will respond well to a GLP-1 receptor agonist.
Professor Gloyn added that an integrated view will be needed to predict the risk of type 2 diabetes taking into account lifestyle and environment, the underlying genetic risk and early life events. To do this sequence data from a person’s genome will need to be combined with lifestyle data and progression biomarkers to achieve useful prediction rates.
Professor Gloyn’s take home messages were that a genetic diagnosis alters treatment and prognosis in monogenic diabetes. The interpretation of genetic variants in known monogenic genes requires domain expertise and integration of data but that ultimately genetics may help precision medicine efforts for type 2 diabetes.
Two very different topics but both Covid-19 research and personalised, or stratified, medicine are on everyone’s lips at the moment, and it will be interesting to see if and when these two fields collide.
Read Lockdown guidance for staying home and safe for people living with diabetes during Covid-19 pandemic
DRWF operations during the Covid-19 health crisis
The DRWF team is working remotely. Covid-19 guidance, particularly where it aligns or impacts with diabetes guidance, is shared as quickly as possible through the DRWF website and social media channels with the aim of making it as easy to understand as possible and a reliable source of latest news.