Is the Gut Microbiome Associated with Residual *-Cell Function and Development of Complications in Individuals with Longstanding Type 1 Diabetes Mellitus

Rationale: It has become apparent that most individuals with type 1 diabetes
mellitus (T1D) have some remaining β-cell function. Individuals with T1D and a
preserved β-cell function have a lower risk of hypoglycemia and diabetic
complications. The factors regulating residual β-cell function are unknown. A
likely mechanism leading to β-cell preservation is regulation of immunological
tone by the gut microbiome. Recently we published in a small pilot cohort
(GUTDM1, METC 2020_105) that residual β-cell function is linked to better
glycemic control (time in range) and linked to specific gut microbiota
composition. Since this cohort was too small to also show a link with presence
of diabetes complications and recruit enough individuals with preserved β-cell
function for confirmatory intervention trials to increase β-cell function, we
will now aim to recruit a larger follow-up cohort to a) investigate whether
residual β-cell function is associated with gut microbiome composition and
circulating immune cell counts in individuals with T1D from the new Diabeter
Center Amsterdam and b) identify 500 potential eligible individuals with
preserved β-cell function.

Objective: 1. To investigate whether T1D individuals with preserved β-cell
function exhibit a distinct gut microbial and circulating immune cell
signature, leading to a reduced incidence of diabetes complications (CVD,
nephropathy, neuropathy, and retinopathy).
2. Identify individuals with preserved β-cell function for diagnostics as well
as future intervention studies to increase β-cell function.
Study design: 10-year longitudinal observational cohort study

a 10 year multicenter logitudinal cohort study

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: This study is considered a low-risk study. The
patient will complete several questionnaires, keep track of a food diary and
collect urine and feces prior to the study visit. At the study visit we will
require a fasted plasma sample, this will slightly increase the chances of a
hypoglycemic episode, largely mitigated because all participants carry a
continues glucose monitor. Additionally, we will calculate BMI, waist
circumference, liver stiffness and measure blood pressure. The questionnaires
inquire about the burden of diabetic complications, socio-economic status and
financial literacy, abdominal complaints and hypoglycemic episodes and
comorbidities associated with diabetes. We argue that the risk and discomfort
associated with this study is similar to the yearly diabetes check-up and
justified in light of the potentially profound insights and novel treatments to
be gained by studying the impact of the gut microbiome on residual β-cell
function in T1D.