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DIETARY PATTERN ANALYSIS IDENTIFIES FOUR CLINICALLY RELEVANT DIET PHENOTYPES IN HYPERMOBILE EHLERS DANLOS SYNDROME (HEDS)

Rabia Topan 1, Janet Kyle 2, Paul Bassett 3, Qasim Aziz 4, Natalia Zarate-Lopez 5, Kevin Whelan 6, Asma Fikree 5

Affiliations

1 Wingate Institute of Neurogastroenterology, London, United Kingdom

2 University of Aberdeen, Aberdeen, United Kingdom

3 Independent Statistical Consultant, Amersham, United Kingdom

4 Wingate Institute for Neurogastroenterology - Centre for Neuroscience and Trauma, London, United Kingdom

5 University College London Hospital, London, United Kingdom

6 King's College London - Diabetes & Nutritional Sciences Division, London, United Kingdom

Summary

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A cross-sectional survey of 470 patients with hypermobile Ehlers-Danlos Syndrome identified four distinct dietary patterns, with the most common being low energy intake, particularly among those attending tertiary clinics and using artificial nutrition.

Four dietary clusters were identified: low energy intake (n=169, most common), vegetarian/health conscious (n=62), prudent/low residue (n=133), and refined/highly processed food (n=106).
Patients with low energy intake were most likely to attend tertiary neurogastroenterology clinics, have dietetic consultations, and use artificial nutrition.
The vegetarian/health conscious group had the lowest depression and gastrointestinal-specific anxiety scores and were most likely to take nutritional supplements.
Patients consuming refined/highly processed foods were youngest, had higher depression, gastrointestinal-specific anxiety, and ARFID scores, and were least likely to attend tertiary clinics or take supplements.
No significant associations were found between dietary patterns and postural orthostatic tachycardia syndrome, mast cell activation syndrome, or disorders of gut-brain interaction.

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Abstract

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known about their dietary patterns and whether this is associated with relevant clinical characteristics.

Aims & Methods

Our aim was to identify dietary patterns in hEDS, phenotype patients according to their dietary patterns and determine whether these patterns are associated with gastrointestinal or other factors. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), past history of Postural orthostatic Tachycardia Syndrome (PoTS) or Mast Cell Activation Syndrome (MCAS), somatic and autonomic symptoms, anxiety and depression, gastrointestinal specific anxiety, Restrictive Food Intake Disorder (ARFID) screen, artificial nutrition use, nutritional supplement use and previous dietetic consultation. The 169 food items on the FFQ were consolidated into 49 food groups and principal components analysis (PCA) was used to derive dietary patterns. Cluster analysis was then used to classify patients into dietary groups. Clinical characteristics were compared between clusters using the Chi-square test, analysis of variance (ANOVA) and Kruskal-Wallis test as appropriate.

Results

470 patients were included in the final analysis, of which four clusters were identified: cluster 1 (n=169) - low energy intake; cluster 2 (n=62) - vegetarian / health conscious; cluster 3 (n=133) - prudent / low residue and cluster 4 (n=106) - refined / highly processed food. Patients in the low energy intake group (cluster 1) were most likely to attend the tertiary neurogastroenterology clinic (p=0.002), have a dietetic consultation (p=0.02) and report previous or current use of artificial nutrition (p=0.03) compared to the other clusters. Patients in the vegetarian / health conscious group (cluster 2) had the lowest depression scores (p=0.03), lowest GI specific anxiety (p=0.005) and interestingly, were most likely to take nutritional supplements (p=0.04). Patients in the prudent / low residue group (cluster 3) and the refined / highly processed food group (cluster 4) had the highest body mass index (p=0.003). Patients in the refined / highly processed food group (cluster 4) were youngest (p<0.001), had higher scores for depression (p=0.03), higher scores for GI specific anxiety (p=0.005) and higher scores for ARFID (p=0.007). They were also least likely to take nutritional supplements (p=0.04) and least likely to attend the tertiary neurogastroenterology clinic (p=0.002). Interestingly, there was no significant association between dietary patterns and PoTS, MCAS or DGBIs.

Conclusion

This is the first study to identify dietary patterns in patients with hEDS. The most common dietary cluster was lower energy intake and this was most likely to be seen in those attending tertiary clinics and utilising artificial nutrition. Whereas those who are on a refined / highly processed food diet tend to be younger and have more psychopathology. Further research is needed to establish how these associations could best be utilised in clinical practice.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Conference

UEG Week Copenhagen 2023

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Various perspectives on nutritional medicine (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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The new era of non-diet treatments in coeliac disease

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The new era of non-diet treatments in coeliac disease

Michael Schumann 1

Affiliations

1 Charité – Universitätsmedizin Berlin, Berlin, Germany

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Paediatrics Small Intestine & Nutrition Primary Care Small Intestine & Nutrition

Session

PGT Opening: How to make and not miss the diagnosis - Coeliac disease across the spectrum

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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After the first biologic failure, the next choice matters: Building confidence beyond conventional targets through deep remission with mirikizumab in CD (Eli Lilly and Company) (Complete Session)

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After the first biologic failure, the next choice matters: Building confidence beyond conventional targets through deep remission with mirikizumab in CD (Eli Lilly and Company) (Complete Session)

Alissa Walsh 1, Marc Ferrante 2, Stefan Schreiber 3

Affiliations

1 Translational Gastroenterology Unit, Oxford University Hospital, Oxford, United Kingdom

2 University Hospitals Leuven, Leuven, Belgium

3 Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany

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Abstract

Publisher

Eli Lilly

Event

UEG Week Barcelona 2026

Session

After the first biologic failure, the next choice matters: Building confidence beyond conventional targets through deep remission with mirikizumab in CD (Eli Lilly and Company)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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Presidential address

Matthias Löhr 1

Affiliations

1 Karolinska Institutet, Stockholm, Sweden

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Abstract

Event

UEG Week Vienna 2024

Session

Opening Plenary

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Journal Podcast

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The impact of COVID-19 pandemic in Gastroenterology: focus on IBD

Katarzyna Pawlak 1, Fernando Magro 2, Candida Abreu 2

Affiliations

1 Department Gastroenterology, Endoscopy Unit, Hospital of the Ministry of Interior and Administration, Szczecin, Poland

2 Hospital de São João, Porto, Portugal

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Abstract

Topics

IBD

Published

2021

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REDUCTIONS IN THE NAFLD FIBROSIS SCORE FROM THE ZENITH-CKD TRIAL SUPPORT EXPLORATION OF ZIBOTENTAN DAPAGLIFLOZIN COMBINATION IN CIRRHOSIS

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REDUCTIONS IN THE NAFLD FIBROSIS SCORE FROM THE ZENITH-CKD TRIAL SUPPORT EXPLORATION OF ZIBOTENTAN DAPAGLIFLOZIN COMBINATION IN CIRRHOSIS

Phil Ambery 1, Peter Greasley 1, Emma Wijkmark 1, Kevin Persson 1, Jan Oscarsson 1, Kristin Fiorino 2, Srivathsa Ravikiran 2, Hiddo J L Heerspink 3,4

Affiliations

1 AstraZeneca, Gothenburg, Sweden

2 AstraZeneca, Gaithersburg, United States

3 University of Groningen, University Medical Center Groningen, Groningen, Netherlands

4 The George Institute for Global Health, University of New South Wales, Sydney, Australia

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Abstract

Introduction

Positive effects on markers of metabolic dysfunction–associated steatotic liver disease (MASLD) have already been demonstrated for sodium–glucose cotransporter-2 (SGLT2) inhibitors. Pre-clinical evidence from rodent models also suggests MASLD benefits of endothelin-A receptor antagonism. Zibotentan, the most selective endothelin A receptor antagonist, is currently under clinical investigation in combination with dapagliflozin for treatment of chronic kidney disease (CKD) and for liver cirrhosis. Advanced CKD is also recognized to occur concomitantly with liver cirrhosis.

Aims & Methods

The aim of this exploratory analysis was to evaluate the effect of zibotentan combined with dapagliflozin and dapagliflozin alone on a non-invasive measure of MASLD in patients with CKD recruited into the ZENITH-CKD phase 2b study.

447 patients in the ZENITH-CKD study were treated for 12 weeks with either zibotentan 0.25 mg in combination with dapagliflozin 10 mg (n = 91), or zibotentan 1.5 mg in combination with dapagliflozin 10 mg (n = 179), or dapagliflozin 10 mg alone (active control) (n = 177). The primary outcome was urinary albumin creatinine ratio at week 12. The presented results are from patients with non-alcoholic fatty liver disease fibrosis score (NFS) > 0.675, indicating high risk for advanced fibrosis and included 39 patients treated with combination therapy with either dose of zibotentan, and 27 patients treated with dapagliflozin alone.

Results

	Zibotentan 0.25 mg/ dapagliflozin 10 mg combination group	Zibotentan 1.5 mg/ dapagliflozin 10 mg combination group	Zibotentan/ dapagliflozin combination groups (pooled)	Dapagliflozin 10 mg alone
Baseline NFS
n	10	29	39	27
Median (Q1, Q3)	1.03 (0.93, 1.23)	1.37 (0.83, 1.77)	1.12 (0.83, 1.58)	1.21 (0.99, 1.62)
NFS reduction at week 12 from baseline
n	6	24	30	20
Median (Q1, Q3)	0.56 (0.40, 0.69)	0.09 (-0.16, 0.29)	0.13 (-0.08, 0.50)	0.26 (-0.30, 0.54)

Conclusion

A reduction in NFS was observed in this small exploratory analysis of patients with CKD and high risk for advanced liver fibrosis across all three active arms of the study. These data support further exploration of the effects of zibotentan and dapagliflozin in patients with liver cirrhosis as part of the ongoing ZEAL part B study. Further data from both the CKD and liver study programs are awaited.

Disclosure

PA, PG, EW, KP, JO, KF and SR are employees of, and hold stakes in, AstraZeneca. HJLH has received funding from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novartis. HJLH has received consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Behring, Dimerix, Eli Lilly, Janssen, Novartis, Novo Nordisk, Roche, Travere Therapeutics and Vifor Pharma.

Event

UEG Week Vienna 2024

Topics

Endoscopy Hepatobiliary Pancreas

Submission format

Late-Breaking Abstract

Session

Between liver and pancreas - Game on: Late-breaking abstracts

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Entering a New Era in Metabolic Dysfunction-Associated Steatohepatitis:Examining the Clinical Implications of Emerging Disease-Specific Therapies (Catalyst Medical Education, LLC.) (Complete Session)

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Entering a New Era in Metabolic Dysfunction-Associated Steatohepatitis:Examining the Clinical Implications of Emerging Disease-Specific Therapies (Catalyst Medical Education, LLC.) (Complete Session)

Naim Alkhouri 1, Elisabetta Bugianesi 2, Michael Trauner 3

Affiliations

1 Arizona Liver Health, Tucson, United States of America

2 AOU Città della Salute e della Scienza University of Torino, Torino, Italy, Torino, Italy

3 None, Vienna, Austria

Summary

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Abstract

Publisher

Catalyst Medical Education

Event

UEG Week Vienna 2024

Session

Entering a New Era in Metabolic Dysfunction-Associated Steatohepatitis:Examining the Clinical Implications of Emerging Disease-Specific Therapies (Catalyst Medical Education, LLC.)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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