1型糖尿病 z-bo 2020-10-23 416

　　Diabetes diagnosed within 6 months of age is generally considered to be caused by a single gene mutation, rather than type 1 diabetes. This perception has recently been challenged by new research.

　　This research was published in Diabetologia, the official journal of the European Association for the Study of Diabetes (EASD). An analysis of a large number of special small patients who were diagnosed with diabetes within 6 months of age found that they were not suffering from known monogenic diabetes, but may be a type 1 diabetes with very early onset; moreover, some factors even suggested that they The earliest possible onset of the disease may begin in the uterine pregnancy stage.

　　Dr. Elizabeth Robertson, Research Director of Diabetes UK, said: "These important findings rewrite our understanding of when type 1 diabetes is onset and when the immune system goes wrong."

　　26 neonatal diabetes genes are currently known. However, 10%-15% of diabetic patients diagnosed within 6 months of age do not carry one of the 26 genetic variants. So, is it possible that there are other causes, such as type 1 diabetes caused by polygenic genetic problems?

　　Therefore, the University of Exeter Medical School team conducted this research. The study included 166 infant patients who were diagnosed with diabetes within 6 months of age and had no known single-gene abnormalities between 2000 and 2019, and compared them with 164 cases of single-gene neonatal diabetes and 152 cases of 6-24 months of age. Children with confirmed polygenic type 1 diabetes were compared.

　　It was found that these 166 study infants who were diagnosed with diabetes within 6 months of age had the typical characteristics of childhood type 1 diabetes: high genetic risk score, autoimmunity, and rapid decline in β-cell function.

　　Specifically, the genetic risk scores of type 1 diabetes (T1D-GRS) of the infants in these studies are indeed high. The T1D-GRS scores of 36% of the infants are higher than 95% of the healthy controls (sample size 4862).

　　This shows that the diabetes of these newborns is not caused by an unknown single gene cause. The research team explained, “Because the distribution of T1D-GRS scores for patients with monogenic diabetes is the same as that of people with non-type 1 diabetes. On the contrary, the high T1D-GRS scores suggest that they may have polygenic type 1 diabetes.

　　Secondly, infant diabetic patients with high T1D-GRS within 6 months of age, their autoantibody positive rate is similar to that of children with diagnosed polygenic type 1 diabetes between 6-24 months of age (41% vs 58%; P = 0.2). This provides another supporting evidence for them to belong to type 1 diabetes.

　　Moreover, the C-peptide levels in their bodies were significantly reduced within 1 year of diagnosis (median<3 pmol/L), which reflected the rapid loss of their ability to secrete insulin in their bodies. In contrast, C-peptide levels in infants with monogenic diabetes were significantly higher (median 64 pmol/L).

　　In addition, the research team also noticed that infants diagnosed with type 1 diabetes within 6 months of age tend to have lower birth weights, and their median birth weight is lower than the international reference standard. Among them, babies diagnosed within 3 months of age have the lowest weight. This increases the possibility that some babies will have reduced insulin secretion due to immune attack in the womb.

　　Based on these findings, the research team believes that type 1 diabetes can appear within 6 months of age. This is a very early-onset type 1 diabetes subtype, and the onset may begin in the pregnancy stage.

　　However, regarding the "extreme" speculation that type 1 diabetes may originate in the uterus, some experts have put forward different opinions, and believe that there is still a lack of direct evidence. Dr. Mikael Knip from the Children’s Hospital of the University of Helsinki in Finland has been studying the early life origin of type 1 diabetes for many years. Although he agrees that the sample size of this study is not small and the design is good, “we have never seen it in the cord blood of newborn babies. Diabetes-related autoantibodies, unless the mother’s (diabetes-related) autoantibodies are positive.” On the other hand, “some risk factors during pregnancy, such as loss of birth weight, may indeed increase the risk of diabetes, but this does not necessarily mean The disease process is induced in the uterus."

　　The corresponding author of the study, Dr. Richard A. Oram of the University of Exeter School of Medicine, said that at present, the research team is planning to study the infant’s immune system more deeply. "Hopefully, it can explain the reasons for the early onset of type 1 diabetes, and provide insights for the development of innovative prevention or treatment methods." Dr. Elizabeth Robertson also agreed that this may "show the key factors of type 1 diabetes from a broader perspective. Prevention and treatment are very important. After all, type 1 diabetes will affect these children for life."