Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)

The human body needs sugar for energy, but too much or too little sugar in the blood is bad for health. To control the amount of sugar in the blood, a molecule called insulin is made by specialised beta cells in the pancreas. In diabetes, beta cells don't make enough insulin which causes high blood sugar levels. In hyperinsulinism, they make too much insulin leading to very low blood sugar levels. Over time, these disorders can lead to serious health problems.

The cause of some cases of diabetes and nearly all cases of hyperinsulinism, is a single spelling mistake in the person's DNA (a variant) that changes how the insulin producing beta cells work.

The overarching aim of the ENDURE study is to understand how DNA variants cause beta cell disorders and to improve understanding of how beta cells work. It is hoped that the insights from this research may lead to new ways to treat and/or improve the lives of people living with beta cell disorders.

Participants will be selected based on having a confirmed disease-causing genetic change that results in beta cells not working properly, or a suitably matched control (same sex, close in age and weight).

Consent: Prospective study participants will be provided with the appropriate participant information sheet (PIS) and Sub-Study Flowchart detailing the study and procedures (specific to the participant's genotype). If interested in participating, the ENDURE study team will contact them to discuss the study in detail and answer any questions and address concerns raised to allow the prospective participant to make an informed decision regarding taking part in the study. For the Imaging Sub-Study, following receipt of verbal consent, participants will be asked to complete a "MRI Safety Checklist Screening Form" that is necessary to screen them prior to booking their MRI scan. Prospective study participants are individuals with a rare genetic mutation that is associated with a monogenic beta cell disorder. The cohort of prospective study participants is diverse in terms of background, primary language, home country. To have an inclusive study set-up, the study team will provide documents that are translated into the participant's (or guardian's) primary language, where English is not the primary language. Additionally, a National Health Service (NHS) appointed interpreter/interpretation service (e.g., Language Line) will be arranged for phone calls and the study visit to ensure clear communication. The participant's clinician may also attend and provide translation.