The impact of family history of type 2 diabetes on clinical heterogeneity in idiopathic type 1 diabetes

Abstract Aim To investigate the impact of family history of type 2 diabetes (T2D) on the clinical phenotypes of patients with idiopathic type 1 diabetes (T1D). Methods In clinically diagnosed T1D cases, a total of 335 idopathic T1D patients were included in the study, after excluding autoimmune T1D using islet autoantibody testing and monogenic diabetes using a custom monogenic diabetes gene panel obtained from clinically diagnosed T1D cases. A semi‐structured questionnaire was used to collect information on the presence of T2D in first‐degree relatives. The demographic and metabolic markers of idiopathic T1D patients were analysed. Subgroup analysis was performed to investigate potential interactions between T2D family history and human leukocyte antigen (HLA) genotypes. Results A total of 18.2% of individuals with idiopathic T1D had a T2D family history, and these individuals were more likely to have features associated with T2D, such as older age of onset, higher body mass index at diagnosis, lower insulin dosage and better beta‐cell function, as indicated by higher levels of fasting C‐peptide and 2‐hour postprandial C‐peptide (all P < 0.05). Additionally, regardless of HLA susceptible genotypes, the impact of family history of T2D was consistently observed in idiopathic T1D patients. Multivariable analyses showed that T2D family history was negatively correlated with the risk of beta‐cell function failure in idiopathic T1D patients ( P < 0.05). Conclusions Family history of T2D may be implicated in the heterogeneity of idiopathic T1D patients.