Coeliac Disease and Type 1 diabetes mellitus: Diabetes related outcomes

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1 Coeliac Disease and Type 1 diabetes mellitus: Diabetes related outcomes Valencia 2014 Professor David S Sanders Royal Hallamshire Hospital & University of Sheffield, UK

2 Sheffield London

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7 Population >6 700,000 4 th largest city in the UK Largest student population Cinemas and sport! Greenest city in England

8 Jessica Ennis Gold Medal in Heptathlon

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13 Question? Do we believe we should be screening adult patients with Type 1 Diabetes for coeliac disease?

14 CD and Type 1 diabetes Intensive glycaemic control is the cornerstone of management 1 Reduced morbidity and mortality 1,2,3 1 The DCCT research group. NEJM 1993;329(14): Tesfaye S et al. EURODIAB IDDM Complications Study. Diabetologia 1996;39: Tesfaye S et al. EURODIAB Prospective Complications Study. NEJM 2005;352: Association between Type 1 diabetes and coeliac disease is well recognised Association of HLA markers or a T cell mediated response 1 Large number of studies in diabetes cohorts looking for coeliac disease Lots of paediatric literature (benefit of screening shown?)

15 Epidemiological database studies suggest that Coeliac Diseases causes increased risk

16 Adult prevalence studies Author Country N Antibody panel Known CD (n) New CD (n) Prevalence (95% CI) Collin, (1989) 16 Finland 195 AGA, ARA ( ) Page, (1994) 17 UK 767 AGA ( ) Sategna-Guidetti, (1994) 18 Italy 383 EMA ( ) Rensch, (1996) 19 USA 47 EMA ( ) De Vitis, (1996) 20 Italy 1114 AGA, EMA ( ) Cronin, (1997) 21 Ireland 101 EMA ( ) Talal, (1997) 22 USA 185 EMA ( ) Sjöberg, (1998) 23 Sweden 848 AGA, EMA ( ) Mahmud, (2005) 24 USA 158 EMA, ttg ( ) Doolan, (2005) 25 Australia 131 EMA, ttg ( ) TOTAL ( )

17 Historical Follow up studies Author N Methodology Effect on glycaemic control Shanahan, (1982) Cross sectional uncontrolled Reduced hypoglycaemia Sategna-Guidetti, (1994) 18 6 Prospective uncontrolled Worse in 4, unchanged in 2 Page, (1994) Prospective uncontrolled No change in fructosamine Cronin, (1997) 21 5 Prospective uncontrolled No change in Hb A1c Acerini, (1998) 71 7 Prospective uncontrolled No change in Hb A1c Kaukinen, (1999) Retrospective and prospective controlled No change in Hb A1c

18 CD and Type 1 diabetes: Limitations? Prevalence ranges from 0% 16.4% (N = ) Only 4 adult studies N>500 Serological assays and glycaemic markers differ Lack of control populations Effect upon glycaemic control uncertain Effect upon quality of life not assessed

19 Contemporary UK Data 1000 patients recruited from 1043 approached (95.8% uptake) Mean age 42.3 years 439 females Known prevalence of coeliac disease in Sheffield is 1% 1 1 Sanders DS et al Eur J Gastroenterol Hepatol 2003;15:407-13

20 Study recruitment flowchart

21 Results 33/1000 Type 1 DM coexistent coeliac disease (3.3%) Compared to background population 12/1200 (1%) Odds ratio 3.4 (95% CI , p=<0.0001)

22 Glycaemic control Mann Whitney U test p<0.0001

23 Glycaemic control on GFD p=0.45

24 Quality of life Cases Controls Score PF RP BP GH VT SF RE MH PCS MCS SF-36v2 Domain All domains cases vs. controls p=>0.1

25 Lipid profile following GFD

26 Cholesterol:HDL ratio p=0.03

27 No differences in peripheral neuropathy

28 Serological testing Panel Sensitivity Specificity PPV NPV EMA/tTG 84.6% 99.2% ttg only 100% 95.2% Only 2 patients missed with EMA/tTG methodology (but needed biopsy anyway) ttg alone lead to 46 unnecessary biopsies

29 Patient Age Sex Symptoms Associations EMA +ve Anaemic 1 82 F Bloating, alternating bowel habit Dermatitis herpetiformis, B12 def No No 2 21 M Nil Nil Yes No 3 42 F TATT B12 def, epilepsy, Yes No 4 43 F Nil Nil Yes No 5 39 M Diarrhoea Vit D def Yes No 6 39 F TATT IDA Yes Yes 7 40 M Bloating Discoid lupus Yes No 8 69 F Nil Hypothyroid, Addisons, IDA Yes Yes 9 53 M F Alternating bowel habit, abdo pain, bloating Alternating bowel habit, abdo pain, bloating, TATT Epilepsy Yes Yes Epilepsy Yes No F TATT, diarrhoea IDA No Yes M Ataxia Nil Yes No

30 Conclusions CD more common in T1DM than general population Worse glycaemic control Similar QoL Improved lipid profile in GFD Leeds JS et al Diabetes Care 2011;34:

31 Everything suggests benefits for looking for coeliac disease in adult patients with Type 1 Diabetes Sjoerd Bakker

32 You appear to need villous atrophy to develop any complications

33 The fly in the ointment?! N=1320 children with CD associated HLA Serological testing at 1 year intervals for 3 years 3.7% were TTG positive BUT ~ 50% spontaneously lost the antibody without starting a GFD Is this a regulatory immune response or immune tolerance? Simell S et al Am J Gastroenterol 2007;102:1 10

34 There is significant fall out!

35 Sometimes it is better to let others objectively judge your data!

36 On-going Research at the Royal Hallamshire Hospital & International GI and Endoscopy Fellowships Contact: Imran Aziz Nina Lewis Mohammed Karajeh John Leeds Kate Evans Dr Steve Barratt Andrew Hopper & Reena Sidhu Marios Hadjivassiliou

37 Royal Hallamshire GI and Liver Unit Research Clinical BSG Hopkins Endoscopy Prize 2012 Small Bowel Endoscopy BSG Clinical Care Award 2011 Small Bowel Endoscopy 2014 Primary Care Services & GI Bleed Unit Health Service Journal Awards 2012 Gastrostomy/PEG Feeding Service Cuthbertson Medal 2011 Nutrition Society & BAPEN (British Association of Parenteral & Enteral Nutrition) Coeliac UK 2010 Patient Healthcare Award Complete Nutrition 2013 Coeliac Healthcare Award European Rising Star Award 2010 Association of National European & Mediterranean Societies of Gastroenterology Medipex Award 2013 Small Bowel Endoscopy