National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Diabetes Obes Metab. 2023 Feb;25(2):417-425. doi: 10.1111/dom.14884. Epub 2022 Nov 2.
To investigate the impact of family history of type 2 diabetes (T2D) on the clinical phenotypes of patients with idiopathic type 1 diabetes (T1D).
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.
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).
Family history of T2D may be implicated in the heterogeneity of idiopathic T1D patients.
探讨 2 型糖尿病（T2D）家族史对特发性 1 型糖尿病（T1D）患者临床表型的影响。
在临床诊断的 T1D 病例中，通过胰岛自身抗体检测排除自身免疫性 T1D，使用从临床诊断的 T1D 病例中获得的定制单基因糖尿病基因panel 排除单基因糖尿病，共纳入 335 例特发性 T1D 患者。采用半结构式问卷收集一级亲属 T2D 患病情况的信息。分析特发性 T1D 患者的人口统计学和代谢标志物。进行亚组分析以探讨 T2D 家族史与人类白细胞抗原（HLA）基因型之间的潜在相互作用。
共有 18.2%的特发性 T1D 患者有 T2D 家族史，这些患者更有可能具有与 T2D 相关的特征，如发病年龄更大、诊断时体重指数更高、胰岛素剂量更低、β细胞功能更好，表现为空腹 C 肽和餐后 2 小时 C 肽水平更高（均 P<0.05）。此外，无论 HLA 易感基因型如何，在特发性 T1D 患者中均观察到 T2D 家族史的影响。多变量分析显示，T2D 家族史与特发性 T1D 患者β细胞功能衰竭的风险呈负相关（P<0.05）。
T2D 家族史可能与特发性 T1D 患者的异质性有关。
