The Prevention & Treatment of Diabetes Dr Elizabeth Robertson Director of Research Diabetes UK

1. The 2019
Royal Pharmaceutical Society/
UCL School of Pharmacy
New Year Lecture

2. The Prevention and Treatment of Diabetes
Dr Elizabeth Robertson
Director of Research, Diabetes UK
Morgan & Richardson, Diabetologia, 2018
Human Islets of Langerhans

3. What is diabetes?

4. What is diabetes?
There are two main types of diabetes
• Type 1 - where the pancreas does not produce any insulin
• Type 2 - where the pancreas does not produce enough
insulin - or the body's cells do not react to insulin

5. Type 1 diabetes: causes
“What once seemed like a
single autoimmune disorder,
with roots in T-cell mediated
attack of insulin-producing β
cells, is now recognised to
result from a complex interplay
between environmental factors
and microbiome, genome,
metabolism, and immune
systems that vary between
individual cases.”
DeMeglio et al Lancet 2018

6. Type 1 diabetes: stages
Greenbaum et al Diabetes 2018

7. Progression of Type 1 diabetes
Long et al Diabetalogia 2018
• Slow progressors – develop islet autoantibodies early in childhood
but can take up to 10 years for a Type 1 diagnosis
• Late starters – develop islet autoantibodies as teenagers or adults
and progress rapidly to a Type 1 diagnosis
• WHY?

8. Type 2 diabetes risk factors

9. Heterogeneity of diabetes
Cluster 1: Severe autoimmune diabetes (SAID)
Cluster 2: Severe insulin-deficient diabetes (SIDD)
Cluster 3: Severe insulin-resistant diabetes (SIRD)
Cluster 4: Mild obesity-related diabetes (MOD)
Cluster 5: Mild age-related diabetes (MARD)
E. Ahlqvist et al Lancet D&E 2018
HbA1c BMI
Age at
diagnosis
B-cell
function
Insulin
resistance

10. Misdiagnosis of diabetes?
Thomas et al, Lancet D&E, 2018
Incidence of genetically defined Type 1 and Type 2
diabetes in the first six decades of life.

11. The crisis we’re
facing

12. Scale of the UK diabetes crisis

13. Scale of the UK diabetes crisis

14. Total number of adults (millions) with diabetes (20-79 years)
Diabetes around the world

15. Scale of the global diabetes crisis
Number of people
with diabetes
worldwide and per
region in 2017 and
2045 (20-79 yrs)

16. Inpatient care in the UK

17. Inpatient care in the UK

18. Investment in diabetes research
in the UK

19. European diabetes research 2002-15
• UK biggest contributor to European diabetes research
• Overall decline in European diabetes research from 45% of
the world output to 33%
Begum et al Diabetic Medicine 2017

20. How we can tackle
the growing crisis

21. Current treatment and prevention
strategies
Strategy Type 1 Type 2
Prevention none diet and lifestyle
Treatment • insulin
• medical
devices
• islet cell
transplant
• diet and lifestyle
• drugs
- metformin
- Sulphonylureas
- Acarbose
- Prandial glucose regulators
- Glitazones
- Incretin mimetics
- DPP4 inhibitors
- SGLT2 inhibitors
• insulin
• bariatric surgery

22. Role for Chemoprevention in Type 2?
Colhoun et al, The Lancet 2004

23. Trends in rates of all-cause mortality among
populations with diagnosed Type 2 diabetes
Gregg et al, Lancet D&E, 2016

24. Need for more targeted use of
existing and new Type 2 drugs
NICE Type 2 diabetes guidelines
Curtis HJ, et al .Diabetes Obes Metab. 2018
DPP4 SGLT2 SU PIO
Metformin
£36 £43 £4 £16

25. Type 2 remission: DiRECT
• Profs Lean (Glasgow) and Taylor
(Newcastle) trialling a low-calorie diet
weight management programme for
Type 2 remission
• Builds on successful Diabetes UK funded research
• 800 cals a day for 8-20 weeks followed by weight
management programme = not a quick fix!
• But can it work long term as part of routine GP care?

26. DiRECT hypothesis
• Too much fat within the liver and pancreas
• prevents normal insulin action
• prevents normal insulin secretion
• Both defects are reversible by substantial weight loss
• Individuals have different levels of tolerance of fat
within the liver and pancreas

27. Two initial small scale studies
11 and 30 participants
100%
0%

28. DiRECT first year results
Remissions by weight-loss category at 12 months
Lean et al, Lancet 2017

29. Responders and non-responders
Taylor et al, Cell Metabolism, 2018

30. Health economic costs of DiRECT
Lean et al, Lancet D & E 2018
£656 £677
£34
£168
£1,223
£0
£500
£1,000
£1,500
£2,000
£2,500
Intervention Control
Primary and secondary care Medications Intervention cost
Components of one-year cost: DiRECT intervention vs. control

31. NHS Diabetes Prevention Programme
(NDPP)
• 100% coverage of England
• 280,000 referrals, 159,600 attended initial
assessment
• 52% of participants attended 8 sessions or
more (out of 13 sessions)*
• Mean weight change for completers -3.2kg (-
3.1 to -3.4kg)*
* Data to March 2018

33. Type 2 prevention plans:
Scotland, Wales & Northern Ireland
NHS
Diabetes
Prevention
Programme
A Healthier Future: Type 2 diabetes
prevention, early detection and
intervention: framework
Diabetes
National
Services
Framework
Diabetes
Strategic
Framework

34. NHS long term plan
(published Jan 7th 2019)
• Prevention of Type 2
• doubling enrolment to NDPP over next 5 years
including new digital option
• 200,000 people
• Remission of Type 2
• test an NHS programme supporting low calorie
diets and weight management for obese people
with Type 2 diabetes
• 5,000 people
www.longtermplan.nhs.uk

35. A vaccine for Type 1?
A peptide immunotherapy relies on injecting small protein
fragments (or peptides) to ‘retrain’ the immune system and
stop it attacking the pancreas, potentially preventing or
slowing down Type 1 diabetes

36. Proinsulin peptide
immunotherapy is safe
Ali et al, Science Translational Medicine, 2017

37. Environmental factors?
Laitinen et al, Diabetes, 2014
D.Hober, Discovery Medicine, 2010
Coxsackie B virus
Gale, Diapedia, 2014
Coxsackievirus B1
- associated with
an increased risk
of β-cell
autoimmunity
Vaccine
developed by
Finnish team -
safe and effective
in mice
Human trial
ongoing

38. Prevention of Type 1?
Steck et al, Diabetes Care, 2015
Progression to diabetes in
children with confirmed
autoantibodies (N = 577)
Ab+, antibody positive
GP, general population
FDR, first degree relative

39. Looking to the
future

40. World-leading UCL diabetes research
Professor Lucy Walker

41. Islet of Langerhans
T cells attack the
pancreatic islets and
destroy the beta cells
Brown: insulin
Blue: T cells
T
T
T

42. 4 of the top 20 most
significantly
upregulated genes
are Tfh genes
T cells responding to islet antigen have a
gene signature of Follicular Helper T cells
Follicular
helper T
cell (Tfh)

43. • People with Type 1 have a gene
signature of follicular helper T cells in
their blood
• design new strategies to halt this
type of damage?
• interfere with cell development?
Follicular
helper T cell
(Tfh)
Can follicular helper T cells be used as
an early indication of the autoimmune
response in Type 1 diabetes?

44. The Future…
• Artificial pancreas
• Microbiome
• AI diagnostics
• Stem cell therapy
• Islet implants
• Psychological interventions
• Social interventions
• And more…

45. Artificial Pancreas
People living with diabetes
• #wearenotwaiting
• Open Artificial Pancreas System
 #OpenAPS
Professor Roman Hovorka, University of Cambridge, has led the world in artificial
pancreas research

46. Role of the Microbiome?
Pollak, Diabelalogia, 2017

47. The future of precision medicine in
diabetes?
• in vivo imaging of beta cell mass and
function
• postprandial glucose indices models
• virtual imaging of patients using digital data
• genetic risk scores
Roden, Cobellini, Rich, Kovatchev, ADA 2018

48. Genetic risk scores
Grubb et al, Diabetes Care 2018

49. • Diabetes is a complex condition
and therefore needs a personalised
approach to prevention, diagnosis,
treatment and care linked to
population scale interventions.
• The importance of translating research into practice –
remission of Type 2 diabetes - an example where
pharmacists could play a key role?
• Strength of diabetes research in the UK and the need
for more investment

50. ‘Overcoming diabetes’
Professor David Taylor
“if governments, health care providers and the
wider public maintain the confidence and
integrity of purpose required to keep investing
in public health measures and effective new
treatments, and to act on the evidence
available about the societal and personal
actions needed to protect health, diabetes and
its consequences will not be major causes of
death or disability by 2050s.”

51. Acknowledgements
Profs N. Morgan & S. Richardson, University of Exeter
International Diabetes Federation Atlas
Prof G. Rayman, Ipswich Hospital
Dr G. Lewison, King’s College London
Prof C. Greenbaum, Benaroya Research Institute, Seattle
Prof L. Groop, Lund University
Prof A. Hattersley, Drs R. Oram, J. Dennis, A. Jones, University of Exeter
Prof K. Gillespie, Dr A. Long University of Bristol
Prof H. Colhoun, University of Edinburgh
Prof N. Satar, University of Glasgow
Prof R. Taylor, University of Newcastle
Prof M. Lean, University of Glasgow
Prof J. Valabhji, Imperial College London, NHS England
Prof M. Peakman, King’s College London
Prof H. Hyöty, University of Tampere
Prof A. Steck, University of Colorado
Prof L. Walker, University College London
Prof R. Hovorka, University of Cambridge
Prof M. Roden, University of Düsseldorf
Prof C. Cobellini, University of Padova
Prof S. Rich, Prof B. Kovatchev, University of Virginia
Professor M. Pollak, McGill University
Drs E. Burns, F. Riley, Diabetes UK
Prof D. Taylor, University College London

52. Thank you
elizabeth.robertson@diabetes.org.uk
@erobertson02