Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Diabetologia. 2021 Mar;64(3):581-590. doi: 10.1007/s00125-020-05342-x. Epub 2020 Dec 17.
AIMS/HYPOTHESIS: Shared aetiopathogenetic factors have been proposed in type 1 diabetes and type 2 diabetes and both diseases have been shown to cluster in families. Characteristics related to type 2 diabetes have been described in patients with type 1 diabetes with a positive family history of type 2 diabetes. We wanted to characterise the family history of type 2 diabetes and its possible effects on the phenotype and genotype of type 1 diabetes in affected children at diagnosis.
A total of 4993 children under the age of 15 years with newly diagnosed type 1 diabetes from the Finnish Pediatric Diabetes Register were recruited (56.6% boys, median age of 8.2 years) for a cross-sectional, observational, population-based investigation. The family history of diabetes at diagnosis was determined by a structured questionnaire, and markers of metabolic derangement, autoantibodies and HLA class II genetics at diagnosis were analysed.
Two per cent of the children had an immediate family member and 36% had grandparents with type 2 diabetes. Fathers and grandfathers were affected by type 2 diabetes more often than mothers and grandmothers. The children with a positive family history for type 2 diabetes were older at the diagnosis of type 1 diabetes (p < 0.001), had higher BMI-for-age (p = 0.01) and more often tested negative for all diabetes-related autoantibodies (p = 0.02).
CONCLUSIONS/INTERPRETATION: Features associated with type 2 diabetes, such as higher body weight, older age at diagnosis and autoantibody negativity, are more frequently already present at the diagnosis of type 1 diabetes in children with a positive family history of type 2 diabetes.
目的/假设：1 型糖尿病和 2 型糖尿病之间存在共同的发病机制，并且这两种疾病在家族中聚集。在有 2 型糖尿病阳性家族史的 1 型糖尿病患者中，已经描述了与 2 型糖尿病相关的特征。我们希望描述 2 型糖尿病家族史及其对诊断时患有 1 型糖尿病的患儿的表型和基因型的可能影响。
我们共招募了来自芬兰儿科糖尿病登记处的 4993 名年龄在 15 岁以下的新诊断为 1 型糖尿病的儿童（56.6%为男孩，中位年龄为 8.2 岁），进行横断面、观察性、基于人群的研究。通过结构化问卷确定诊断时的糖尿病家族史，并分析诊断时的代谢紊乱标志物、自身抗体和 HLA Ⅱ类遗传学标志物。
2%的患儿有直系亲属，36%的患儿有 2 型糖尿病的祖辈。父亲和祖父患 2 型糖尿病的比例高于母亲和祖母。有 2 型糖尿病阳性家族史的患儿在诊断为 1 型糖尿病时年龄更大（p<0.001），体重指数更高（p=0.01），且更常检测到所有糖尿病相关自身抗体阴性（p=0.02）。
结论/解释：与 2 型糖尿病相关的特征，如更高的体重、更年长的发病年龄和自身抗体阴性，在有 2 型糖尿病阳性家族史的儿童中，已经更频繁地出现在 1 型糖尿病的诊断中。
