Microbiome in the Acute Stage of New Onset Paediatric Type 1 Diabetes

Overview

The goal of this observational study is to learn more about the microbiome and metabolome of children with type 1 diabetes (T1D). The main questions it aims to answer are: 1. Do the microbiome and metabolome play a role in the onset and presentation of T1D? 2. How do the microbiome and metabolome evolve during the early stages of T1D? 3. Are there are differences in the microbiome or metabolome of children who present with diabetic ketoacidosis (DKA) versus those who present without DKA, and between those who present with mild, moderate or severe DKA? 4. Is there an association between the microbiome or metabolome and glycaemic control during the first year of diagnosis? 5. Is there an association between the microbiome or metabolome and beta cell reserve after one year of T1D disease?

T1D is caused by autoimmune-mediated destruction of pancreatic beta cells. This leads to a complete deficiency of insulin. Individuals diagnosed with T1D require life-long exogenous insulin replacement to achieve glucose homeostasis and, ultimately, to survive. Although there is an underlying genetic predisposition to developing T1D, the trigger is multifactorial and likely includes environmental factors. Several large cohort studies have identified differences in the microbiome in those with T1D compared to healthy controls and suggested that it may have a role in the pathogenesis of T1D. It is not yet clear if changes in the microbiome are involved in the pathogenesis of beta-cell destruction or are an effect of the disease state. When children present with T1D for the first time, their blood glucose levels are elevated. Some children will present with life threatening DKA in which there is metabolic dysfunction and, in some cases, end organ damage. This study will examine the microbiome and metabolome of children with newly diagnosed T1D during their initial hospital admission, and describe the changes that occur in the microbiome and metabolome as these individuals are commenced on insulin and return to normal glucose homeostasis. The study will also compare the microbiome and metabolome of children presenting with and without DKA to establish if there are particular patterns of microbial diversity which are more common in one group. The study also aims to establish if there is an association between the microbiome or metabolome and glycaemic control during the first year of T1D diagnosis. The study will also investigate associations between the microbiome and metabolome, and beta cell reserve after the first year of T1D disease.