Clinical, bio­chemical and genetic characteristics of familial forms of type 1 diabetes

BACKGROUND: Familial clustering of type 1 diabetes (T1D) highlights the importance of genetic and environmental factors in the pathophysiology of diabetes mellitus (DM). It could be the key to understanding of new immunological and genetic characteristics of T1D.

AIM: To study the clinical, biochemical, immunological and genetic characteristics of children with familial forms of T1D.

MATERIALS AND METHODS: A single-center cross-sectional study included 267 patients with familial T1D and 681 patients with sporadic T1D. Clinical and metabolic characteristics, beta cell autoantibodies and HLA class II genetics from patients with T1D hospitalized to Endocrinology Research Centre Moscow between 2016 and 2023 were analyzed.

RESULTS: The median age of onset of DM was significantly lower in children with familial T1D (5,2 [3,0; 8,0] vs 6,4 [3,6; 9,2], p<0,001). Children with sporadic T1D had diabetic ketosis or diabetic ketoacidosis (DKA) at presentation more frequently (90,3% vs 74%, p<0,001). Among the sib-pair groups 50,5% of first-affected siblings and 19,5% of second- and third-affected siblings had DKA at presentation, while in children from parent-offspring subgroup DKA episodes were observed in 21% of patients (p<0,001). IAA and GAD antibodies were more frequent in familial cases (p<0,013, p<0,003). In our groups, no significant differences in metabolic compensation of the T1D were found. HLA haplotypes associated with an increased disease risk DRB1*04-DQA1*03:03-DQB1*03:02 and DRB1*07-DQA1*02:01-DQB1*02:02 were more common in children with familial T1D (p<0.001 and p<0.001), while the protective haplotype DRB1*08-DQA1*04:01-DQB1*04:02 was more frequent in sporadic forms.

CONCLUSION: Due to our study familial forms of T1D are characterized by an earlier age of onset, a smaller risk of DKA at presentation, as well as features of the immunological profile and predisposing and protective HLA haplotypes presentation. We believe more studies are required in the future to look for risk factors and pathogenesis unserstanding.

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