Mauras Nelly, Ma Qianheng, Weinzimer Stuart A, White Neil H, Tsalikian Eva, Buckingham Bruce, Fox Larry A, Tamborlane William, Arbelaez Ana Maria, Tansey Michael, Aye Tandy, Cato Allison, Hershey Tamara, Englert Kim, Marzelli Matthew, Jo Booil, Reiss Allan
Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Health, Jacksonville, FL.
Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA.
Diabetes. 2025 Aug 1;74(8):1417-1426. doi: 10.2337/db24-0684.
UNLABELLED: Type 1 diabetes has detrimental effects in white matter microstructure. In a longitudinal study, we investigated whether these reported findings change as children grow and enter puberty. At study entry, there were 143 children with type 1 diabetes and 71 control participants without diabetes, 4-9 years old. Brain MRI using diffusion tensor imaging, neurocognitive, and glycemic assessments were performed four times across 6-8 years of follow-up. Longitudinal mixed-effects modeling was used to examine changes in fractional anisotropy (FA), axial diffusivity (AD) (measures of myelination and fiber integrity), radial diffusivity (RD) (axonal leakage), and mean diffusivity (MD) (average diffusion). Associations with glycemic and cognitive measures were assessed. We observed in 182 children (121 type 1 diabetes vs. 61 control participants) who had testing at time 4 that FA increased, and RD, AD, and MD decreased significantly in both groups, with no differences between groups for FA, RD and MD over time. However, children with diabetes had lower AD than control participants at 6-10 years. Differences were not detected at 12 years (age imputed from data), when in puberty. Higher blood glucose levels are associated with lower FA and higher RD and MD. Higher glucose percentage time-in-range was associated with higher FA, reflecting better fiber integrity and myelination and higher cognitive metrics. Within the diabetes group, AD and MD showed no association with neurocognitive outcomes. In summary, white matter AD was decreased in children with diabetes, less so during puberty, and FA was reciprocally related to hyperglycemia. These data suggest continued negative impact of chronic hyperglycemia in the developing brain. ARTICLE HIGHLIGHTS: Type 1 diabetes has detrimental effects in white matter in young children. We performed a longitudinal study using brain MRI (diffusion tensor imaging) and cognitive assessments in 4- to 9-year-old children, control participants without diabetes (n = 71) and with type 1 diabetes (n = 143), plus continuous glucose monitoring, to assess changes at four time points as children grow over 6-8 years. White matter myelination and fiber integrity were assessed using axial diffusivity, which was decreased in the diabetes versus control group, less so during puberty, and fractional anisotropy was reciprocally related to hyperglycemia. Data suggest continued negative impact of chronic hyperglycemia in the developing brain.
未标注：1型糖尿病对脑白质微观结构有不利影响。在一项纵向研究中，我们调查了随着儿童成长并进入青春期，这些已报道的结果是否会发生变化。研究开始时，有143名1型糖尿病儿童和71名无糖尿病的对照参与者，年龄在4至9岁。在6至8年的随访期间进行了4次使用扩散张量成像的脑部MRI、神经认知和血糖评估。使用纵向混合效应模型来检查分数各向异性（FA）、轴向扩散率（AD）（髓鞘形成和纤维完整性的指标）、径向扩散率（RD）（轴突泄漏）和平均扩散率（MD）（平均扩散）的变化。评估了与血糖和认知指标的关联。我们观察了182名在第4次测试时有数据的儿童（121名1型糖尿病儿童与61名对照参与者），发现两组的FA均增加，而RD、AD和MD均显著降低，随着时间推移，两组在FA、RD和MD方面没有差异。然而，糖尿病儿童在6至10岁时的AD低于对照参与者。在12岁（根据数据推算年龄，处于青春期）时未检测到差异。较高的血糖水平与较低的FA以及较高的RD和MD相关。较高的血糖处于目标范围内的时间百分比与较高的FA相关，反映出更好的纤维完整性、髓鞘形成和较高的认知指标。在糖尿病组中，AD和MD与神经认知结果无关联。总之，糖尿病儿童的脑白质AD降低，在青春期降低程度较小，且FA与高血糖呈负相关。这些数据表明慢性高血糖对发育中的大脑持续产生负面影响。 文章亮点：1型糖尿病对幼儿脑白质有不利影响。我们对4至9岁的儿童进行了一项纵向研究，包括无糖尿病的对照参与者（n = 71）和1型糖尿病儿童（n = 143），使用脑部MRI（扩散张量成像）和认知评估，外加持续血糖监测，以评估儿童在6至8年成长过程中四个时间点的变化。使用轴向扩散率评估脑白质髓鞘形成和纤维完整性，糖尿病组与对照组相比轴向扩散率降低，在青春期降低程度较小，分数各向异性与高血糖呈负相关。数据表明慢性高血糖对发育中的大脑持续产生负面影响。
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