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Royal Pharmaceutical Society UCL School of Pharmacy New Year Lecture 2019

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

Published in: Technology
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Royal Pharmaceutical Society UCL School of Pharmacy New Year Lecture 2019

  1. 1. The 2019 Royal Pharmaceutical Society/ UCL School of Pharmacy New Year Lecture
  2. 2. The Prevention and Treatment of Diabetes Dr Elizabeth Robertson Director of Research, Diabetes UK Morgan & Richardson, Diabetologia, 2018 Human Islets of Langerhans
  3. 3. What is diabetes?
  4. 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. 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. 6. Type 1 diabetes: stages Greenbaum et al Diabetes 2018
  7. 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. 8. Type 2 diabetes risk factors
  9. 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. 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. 11. The crisis we’re facing
  12. 12. Scale of the UK diabetes crisis
  13. 13. Scale of the UK diabetes crisis
  14. 14. Total number of adults (millions) with diabetes (20-79 years) Diabetes around the world
  15. 15. Scale of the global diabetes crisis Number of people with diabetes worldwide and per region in 2017 and 2045 (20-79 yrs)
  16. 16. Inpatient care in the UK
  17. 17. Inpatient care in the UK
  18. 18. Investment in diabetes research in the UK
  19. 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. 20. How we can tackle the growing crisis
  21. 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. 22. Role for Chemoprevention in Type 2? Colhoun et al, The Lancet 2004
  23. 23. Trends in rates of all-cause mortality among populations with diagnosed Type 2 diabetes Gregg et al, Lancet D&E, 2016
  24. 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. 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. 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. 27. Two initial small scale studies 11 and 30 participants 100% 0%
  28. 28. DiRECT first year results Remissions by weight-loss category at 12 months Lean et al, Lancet 2017
  29. 29. Responders and non-responders Taylor et al, Cell Metabolism, 2018
  30. 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. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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
  35. 35. Proinsulin peptide immunotherapy is safe Ali et al, Science Translational Medicine, 2017
  36. 36. 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
  37. 37. 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
  38. 38. Looking to the future
  39. 39. World-leading UCL diabetes research Professor Lucy Walker
  40. 40. Islet of Langerhans T cells attack the pancreatic islets and destroy the beta cells Brown: insulin Blue: T cells T T T
  41. 41. 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)
  42. 42. • 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?
  43. 43. The Future… • Artificial pancreas • Microbiome • AI diagnostics • Stem cell therapy • Islet implants • Psychological interventions • Social interventions • And more…
  44. 44. 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
  45. 45. Role of the Microbiome? Pollak, Diabelalogia, 2017
  46. 46. 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
  47. 47. Genetic risk scores Grubb et al, Diabetes Care 2018
  48. 48. • 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
  49. 49. ‘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.”
  50. 50. 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
  51. 51. Thank you elizabeth.robertson@diabetes.org.uk @erobertson02

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