Targeting treatment and improving lives in the diabetes community
Submitting InstitutionsUniversity of Brighton,
University of Sussex
Unit of AssessmentAllied Health Professions, Dentistry, Nursing and Pharmacy
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Immunology
Summary of the impact
Research from the University of Brighton's Diabetes Research Group (DRG)
has underpinned the translation of beta-cell replacement therapy into
clinical application for the treatment of type 1 diabetes (T1D) to
establish the world's first government-funded islet transplant service at
six new UK islet-transplant centres. As a consequence, the first 65
successful islet transplants were performed, reducing the incidence of
hypoglycaemic events by >95% and providing a life- changing therapy for
patients. Through a leadership role in Diabetes UK, BONE integrated the
interests of stakeholders and professionals to establish a new model for
diabetes care. With the Juvenile Diabetes Research Foundation, in 2013 he
launched in Parliament the first UK T1D Research Roadmap.
Diabetes research at the University of Brighton has established a
progressive research base across 20 years. The DRG applies
clinically-reflective model systems and human tissue studies to determine
the disease mechanisms underpinning the causes, development and
progression of diabetes. Early work [reference 3.1] used biopsies to
relate histological change to rodent cell activation during the course of
pre-diabetes. This study discovered a significant rise in a coenzyme late
in the progression of pre-diabetes that helped to modify knowledge about
cell destruction processes. This developmental work documenting the
natural history of the disease processes in models of T1D has progressed
to studies on newly diagnosed diabetes in humans.
Reported findings [3.2, 3.3], using a unique collection of T1D
pancreases, have characterised the inflammatory infiltrate in T1D and
provided the first direct evidence that a common enteroviral infection is
capable of triggering development of diabetes in genetically susceptible
individuals. This work was identified as a `Research Highlight' in Nature.
Further research demonstrated for the first time that there is an
increased islet cell proliferation in patients with recent-onset T1D [3.4,
3.5] thereby identifying new therapeutic targets and treatments for the
cure and prevention of T1D (Juvenile Diabetes Research Federation
International-Research Priority Area). These studies were selected by the
Editor of Diabetologia — the premier European diabetes journal as
an `Editor's choice' article and also triggered a full commentary paper in
the same journal. This research was supported by the DRG's participation
in an EU programme, the IREN Consortium, which established a European
Centre for `Beta Cell Regenerative Medicine', including central facilities
for: (a) human stem cells; (b) human pancreatic islets; (c) viral vector
construction and; (d) microarray genetic and proteomic analyses.
University of Brighton researchers led the development of
cellular/molecular methodologies and model systems for generating,
characterising and testing replacement cells and tissues suitable for
Research involving model systems expanded previous work started by
MACFARLANE and SHAW at Newcastle and went on to develop a
glucose-responsive beta-cell line to produce a new and abundant
alternative source of insulin producing cells suitable for transplantation
and treatment of T1D [3.6]. This work has configured alternative
beta-cells as surrogates of native islets and these 3D islet-like clusters
have proved an ideal replacement for non-human islets in studies to
improve outcomes in human islet transplantation. These research
achievements have been driven by EU programmes aimed at improving
understanding of T1D and developing better treatments for people living
with the disease. The TONECA Co-ordination Action promoted and supported
the networking and coordination of research and innovation activities in
the field of T1DM by combining expertise and providing open access to new
research results throughout the EU. The University of Brighton led one of
the four main scientific Work-packages (WP3 — in-vivo model systems) and
acted as the UK Regional Coordinating Centre, with responsibility for
communication between scientists, physicians and patients and their
national organisations (professional and patient). The ongoing PEVNET
research programme is detecting the persistent enterovirus infection
leading to inflammation and damage of the pancreas and stopping the
subsequent development of disease. The work on the detection of viruses
(Workpackage 3) is the responsibility of the collaborative research
partnership led by key investigators BONE (Brighton), Morgan (Exeter) and
Foulis (Glasgow). The University of Brighton is the co-ordinating centre
of the recently awarded NEXT Collaborative Project, which is developing
nano-engineered pancreatic islets to investigate adverse immune reactions
and develop immune-shielded islets suitable for transplantation into
non-systemically immune-suppressed diabetic patients. The tissue
engineering of the beta-cells (WP2) and the construction and in-vitro
testing of the chimeric islet grafts are the responsibility of University
of Brighton researchers MACFARLANE, BONE and SANTIN.
||Professor of Cell and Molecular Biology
(June 1992–to date).
||Reader (Oct 2006–to date).
||Research Fellow (Oct 1994–Oct 1996),
Research Fellow (Nov 1998–Mar 2001), Senior Research Fellow (Apr
2001–Mar 2004) Senior Lecturer (Apr 2004–May 2006), Principal
Lecturer and Reader (June 2006–July 2010), Professor of Tissue
Regeneration (Aug 2010–to date).
References to the research
[3.1] DAVIES, A.J., BONE, A.J., WILKIN, T.J., ROKOS, H. and COLE, D.R.
(1994) Serum biopterin — A novel marker for immune activation during
prediabetes in the BB rat. Diabetologia, 37, pp.466-471. [Quality
validation: leading peer-reviewed journal].
[3.2] RICHARDSON. S.J., WILLCOX. A., BONE. A.J., FOULIS, A.K. and MORGAN,
N.G. (2009) The prevalence of enteroviral capsid protein vp1
immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia,
52, pp.1143-115. [Quality validation: 105 cites].
[3.3] WILLCOX. A., RICHARDSON, S.J., BONE, A.J., FOULIS, A.K. and MORGAN,
N.G. (2009) Analysis of islet inflammation in human type 1 diabetes. Clinical
Experimental Immunology, 155, pp.173-181. [Quality
validation: 108 cites].
[3.4] WILLCOX, A., RICHARDSON, S.J., BONE, A.J., FOULIS, A.K. and MORGAN,
N.G. (2010) Evidence of increased islet cell proliferation in patients
with recent onset type 1 diabetes. Diabetologia, 53, pp.2020-2028.
[Quality validation: leading peer-reviewed journal].
[3.5] WILLCOX, A., RICHARDSON, S.J., BONE, A.J., FOULIS, A.K. and MORGAN
N.G. (2011) Immunohistochemical analysis of the relationship between islet
cell proliferation and the production of the enteroviral capsid protein,
vp1, in the islets of patients with recent-onset type 1 diabetes. Diabetologia:
Short Communication, 54, pp.2417-2420. [Quality validation: leading
[3.6] ALDIBBIAT, A., MARRIOTT, C.E., SCOUGALL, K.T., CAMPBELL, S.C.,
HUANG, G.C., MACFARLANE, W.M. and SHAW, J.A.M. (2008) Inability
to process and store proinsulin in transdifferentiated pancreatic acinar
cells lacking the regulated secretory pathway. Journal of
Endocrinology, 196, pp.33-43. ISSN 0022-0795. [Quality validation:
leading peer- reviewed journal].
Peer-reviewed research grants:
BONE (Steering Committee Member), `Islet Research European Network
[IREN]: Bioengineered cells for gene therapy of diabetes mellitus' EU
Commission BIOMED 2 Concerted Action (18 partners). 1998-2002. Total
BONE (Work-package Leader) Coordination Action on the aetiology,
pathology and prediction of type 1 diabetes in Europe (Project acronym:
TONECA) EU Sixth Framework Programme Priority 1.1.1: Life Sciences,
Genomics & Biotechnology for Health. (28 partners). 2004-2008. Total
BONE together with Morgan, Foulis and 13 EU partners, `PEVNET —
Persistent virus infection as a cause of pathogenic inflammation in type 1
diabetes — an innovative research programme of biobanks and expertise.' EU
7th FP Collaborative Project. 2011-2016. Total funding: €5.99m.
MACFARLANE, BONE and SANTIN and 4 EU partners — HEI x1, SME x3), `NEXT —
Nano engineering for cross tolerance: a new approach for bioengineered,
vascularised, chimeric islet transplantation in non-immunosuppressed
hosts.' EU 7th FP Collaborative Project. 2013-2016. Total
Details of the impact
The World Health Organisation predicts that more than 30 million people
will be diagnosed with the T1D disease by 2030, classifying it as a global
epidemic. University of Brighton researchers provide the expertise to
target treatment and improve lives in the diabetes community through:
Establishing the world's first government-funded islet transplant
service: The University of DRG's work on the isolation and
functional characterisation of pancreatic beta and surrogate
insulin-producing cells provided the basic research underpinning the
establishment of the UK Islet Transplant Consortium. The Consortium,
chaired by Professor James Shaw (Newcastle), prepared a successful bid to
the National Commissioning Group for NHS funding and NICE approval of an
integrated UK NHS Islet Transplant Programme. The Programme, launched
nationally in 2008, is the world's first government-funded islet
transplant service dedicated to patients with type 1 diabetes. This
programme saw the establishment of six transplant centres that provide a
cost-effective national programme for islet transplantation. These centres
were commissioned to deliver a cure for recurrent life-threatening
hypoglycaemia (sources 5.1, 5.2, 5.3).
About one third of people with type 1 diabetes will experience a severe
hypoglycaemic event each year, requiring intervention and treatment from
others. For people who experience multiple severe events, an islet
transplant is life-changing therapy. Islet transplantation involves
separating out insulin-producing islet tissue from a donor pancreas and
transplanting the islets by simple injection into the liver of the
patient. These islets develop their own blood supply and produce insulin
as required. Islet transplants have been successfully performed on 65
patients between April 2008 and March 2013, with a reduction in severe
hypoglycaemic events (>95%) and improved glycaemic control (5.2, 5.4).
The frequency of severe hypos was, on average, reduced from 23 per person
per year to less than 1 per person per year and overall insulin
requirement was halved in these patients. This simple procedure makes the
most unmanageable form of this condition manageable. These low-impact
transplants are performed under local anaesthetic, taking less than 30
minutes, with patients returning home on the same day free from the burden
of insulin injections, finger-prick blood glucose testing and the fear of
night-time hypoglycaemic episodes. Patient, family and carer education is
an essential aspect of the service delivery to ensure long-term and
sustained improvement. MACFARLANE and BONE continue to provide advice to
the Consortium as members of the Scientific Advisory Board.
Promoting a wider understanding of the lifestyle issues associated
with living with diabetes: BONE's earlier work with the British
Diabetic Association (subsequently Diabetes UK) as a member of the UK
Advisory Council and Professional Advisory Council Executive, helped the
Organisation move from a predominantly clinician-led professional
association to the largest organisation in the UK working for people with
diabetes. This has helped break down barriers between clinicians and
patients through the empowerment of a range of stakeholders. Currently
Diabetes UK has a nationwide network of >300 voluntary groups with
300,000 supporters and 6,000 healthcare professional members. BONE'S
involvement in this transition was as a member of the Executive Group
(Hon. Secretary), which developed the current Diabetes UK Governance
Structure. The Expert Group (Science and Research) he chaired was the
first to directly engage patients and lay members in priority setting,
which has changed the nature of care in the diabetes community. This is a
practice subsequently adopted by the other Expert Groups that feed into
the UK Advisory Council. This increased leadership role for the lay
membership of Diabetes UK required a significant culture change from both
healthcare professionals and lay persons alike. The major impacts have
been a wider understanding of the lifestyle issues associated with living
with diabetes from the healthcare professionals and a heightened sense of
engagement of patients and their carers with the work of Diabetes UK. In
recognition of this, BONE won an Excellence Award for Outstanding Services
to the Advisory Council of Diabetes UK in 2008.
Raising awareness with key policy makers: Brighton DRG works
closely, in an advisory capacity, with the major national (Diabetes UK)
and international (Juvenile Diabetes Research Foundation — JDRF) diabetes
charities and professional bodies (International Diabetes Federation —
IDF) (5.5). This work has raised awareness of what living with diabetes
involves and the impact it has on the UK. The University of Brighton DRG,
along with Brighton MP Caroline Lucas, led the JDRF call for the
government to provide additional investment in type 1 diabetes research at
the first-ever `Type 1 Parliament' lobbying event at the Houses of
Parliament — 25 April, 2012. Delegates included 60 patients with T1D and
over 70 MPs, and the audience was made up of 300 people from key groups
including healthcare professionals, corporate supporters and journalists.
This lobbying event led to the launch, in June 2013, of the `Type 1
Diabetes Research Agenda Roadmap for the UK' with the Brighton DRG
selected to lead the beta cell research priority area (5.6). This roadmap
highlights gaps in resources, has helped to dovetail internationally
relevant research priorities, evidenced issues in career structures, grant
types and funding stability across the community, thus providing relevant
information to government, and enabling them to leverage more funding into
Increasing public engagement and promoting understanding of diabetes:
The University of Brighton DRG recently made a short film with the
organiser of the Sussex Diabetes Gateway, a peer support group for young
people with diabetes (5.7). This powerful film describes the impact that
involvement with members of the DRG is having in helping youngsters
improve their quality of life and their diabetes control. The SD Gateway
is one of many local diabetes voluntary groups that have enthusiastically
attended the `Open Lab' sessions run by the DRG at the University of
Brighton, promoting public and patient awareness of diabetes research.
Other local community groups that visit the University of Brighton DRG and
which the DRG visit regularly to give presentations include the Redhill
Obesity Community Engagement Group, the Brighton Voluntary group and
diabetes patient support groups from Burgess Hill and Hayling Island.
MACFARLANE and BONE are regular invited speakers at JDRF public awareness
events throughout the UK, which provide research updates and opportunities
for families affected by diabetes to talk with researchers and understand
how research teams like the University of Brighton DRG are working
together to achieve JDRF's mission to cure, treat and prevent type 1
diabetes. Recent events that have led directly to increased donations to
JDRF include — `The artificial pancreas' — Newcastle, November 2011;
`Discovery Day' — Brighton, November 2011; JDRF Patrons' Club `Paths to
the perfect pancreas' — London, October 2012.
Sources to corroborate the impact
5.1 Information on the UK NHS Islet Transplant Programme. Available at: www.nhsbt.nhs.uk/triennial-report/organ-donation-and-transplantation/allocation-of-organs/
[Accessed: 2 November 2013].
5.2 Diabetes UK, `Diabetes treatments' [online]. Available at: http://www.diabetes.org.uk/Guide-to-diabetes/Treatments/Islet-transplants/?print=2
[Accessed: 2 November 2013]. Guide to treatments that confirms the role of
the first government-funded transplant centre and that 95 islet
transplants had been performed in 65 people in the UK.
5.3 National Specialised Commissioning Team, Service Specification.
Available at: http://www.specialisedservices.nhs.uk/library/36/Service_Specification_and_Standards___I
[Accessed: 2 November 2013]. This document describes the effects of islet
transplantation including proven benefits for those who suffer from
recurrent episodes of severe hypoglycaemia.
5.4 Young Diabetologists & Endocrinologists (2012), `Referral
criteria for islet transplantation.' Available at:http://www.youngdiabetologists.org.uk/etools/guidelines/islet
[Accessed: 2 November 2013]. Confirmation that 96% of all transplants were
functioning at one month, and have been maintained long-term Severe
hypoglycaemia was reduced by >95% and the UK clinical islet transplant
programme has attained its goals of preventing recurrent severe
hypoglycaemia, improving glycaemic control and maintaining satisfactory
5.5 Testimonial available from Head of Research Communication at JDRF,
confirming how the Brighton DRG work is contributing to JDRF's mission to
finding the cure and the impact of the diabetes research agenda roadmap.
5.6 JDRF (2013) Type 1 Diabetes Research Agenda Roadmap Report. Available
[Accessed: 2 November 2013]. Roadmap Delivered to Parliament 12 June 2013.
Brighton's research appears on pages 20-21.
5.7 The Sussex Diabetes Gateway. Available at: http://www.sussexdiabetes.org.uk/
[Accessed: 2 November 2013].