Exploring the severity and early onset of familial type 1 diabetes in Romania: genetic and microbiota insights

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic condition characterized by pancreatic autoimmunity and destruction of the insulin producing beta-cells. The risk of familial type 1 diabetes (FT1DM) is greater in families with paternal T1DM. The children with paternal FT1DM have a more severe form of the disease with diabetic ketoacidosis. Three families with FT1DM, out of which two with paternal diabetes and daughters diagnosed with this disease, and one family with sibling FT1DM were evaluated between 2019-2021 in the Pediatric Diabetes and the Diabetes, Nutrition and Metabolic Departments of a tertiary hospital. Clinical, biological, and genetic evaluations were performed, together with an assessment of the gastrointestinal microbiota. The Romanian children with FT1DM had a more severe onset, a median of age at onset of 9 years old and a genetic predisposition with positive HLA DR3/R4, DQB1*02:01. The protecting allele, DPB1*04:01, was found only in the siblings with FT1DM. A gastrointestinal dysbiosis, characterized by pro-inflammatory bacteria, with high levels of Enterobacteriaceae and Candida, was observed in the gut microbiota. This is the first case series of FT1DM in Romanian patients that shows the presence of genetic determinants but also a pathological microbiota which may determine a more severe and an early-age onset of disease.