Metabolic VEDS Research Study

Metabolic phenotyping in individuals with vascular Ehlers-Danlos Syndrome (vEDS) 

Objective

The study will explore whether people with vascular Ehlers–Danlos syndrome (vEDS) have any differences in the way their body stores and uses fat (adipose tissue), compared with people who do not have vEDS. At this stage, we do not know if such differences exist or whether they affect health – this is what the study is designed to find out.

Some small research studies have looked at body scans of people with vEDS. On average, they found that people with vEDS had a little more fat around the tummy and chest and a little less in the arms and legs, even when their weight was in the normal range.

This study is trying to find out whether these small differences, and certain hormones made by fat tissue, are part of the overall vEDS picture, and whether they might be linked in any way to blood-vessel health or diabetes.

Fat tissue is important for keeping the body healthy. It stores extra energy, but it also produces chemical messengers that help to control things like blood sugar and cholesterol.

In the general population, when fat tissue cannot expand or work properly, fat can build up in places like the liver and muscles instead. This can be linked with higher blood sugar, higher cholesterol and a greater risk of diabetes and heart disease.

We do not yet know whether this happens in vEDS – this is one of the questions this study hopes to explore.

Methods

In this study,we will invite 15 adults with genetically confirmed vEDS to take part, along with a comparison group of people of similar age, sex and weight who do not have vEDS.

Everyone will be asked to attend a single research visit at Addenbrooke’s Hospital, Cambridge. During the visit, participants will have measurements of body-fat distribution (using a DEXA scan), a liver scan, blood tests, and a standard oral glucose tolerance test (drinking a sugary drink with blood samples taken before and after).

Some people may also choose to provide a small fat biopsy under local anaesthetic, to allow more detailed analysis of tissue structure. The main aim is to see whether people with vEDS show any differences in fat distribution and in how their body handles insulin, compared with those without vEDS.

People with vEDS can bruise or bleed more easily, so all procedures will be done by experienced staff using extra care, and you can stop any part at any time if you are uncomfortable.

Your safety will always come first. The longer-term aim of this research is to improve medical advice for people with vEDS, including clearer guidance on heart and blood vessel risk and how best to monitor and manage this.

Eligibility

To participate in this study you must have a genetically confirmed diagnosis of vascular Ehlers-Danlos syndrome (vEDS) and you are between 18-85 years old and resident in the UK.

• Participants will require a laboratory report from an accredited diagnostic laboratory (e.g., NHS or equivalent) confirming a pathogenic or likely pathogenic COL3A1 variant.
• Individuals with a COL3A1 variant of uncertain significance (VUS) will not be eligible for inclusion.
• All pathogenic or likely pathogenic COL3A1 variants will be eligible, with particular interest in glycine substitutions, though not restricting recruitment solely to this subgroup.
  

Principal Investigator

Dr Agnieszka Jakubowska, Clinical Research Associate/ Specialist Registrar (ST5) in Metabolic Medicine and Chemical Pathology at the University of Cambridge.

This research study will be overseen by Professor Sir Stephen O’Rahilly who is a world expert in diabetes, obesity, and metabolic health at the Institute of Metabolic Science, University of Cambridge.