Skeletal Health in Youth with Type 1 Diabetes and Gender Diversity

青春期是构建骨骼和干扰青春期危害内分泌功能的关键窗口 峰值骨量增加。在我们的父母研究中，我们发现患有1型糖尿病(T1D)的儿童发生了改变 与对照组相比，峰值骨积累开始时的骨结构。我们的初步数据显示 高分辨率外周定量CT(HRpQCT)显示的骨小梁面积在T1D时减小。这一赤字是 与更严重的血糖有关，包括连续血糖监测(CGM)显示的高血糖时间延长 并通过皮肤自发荧光(SAF)增加晚期糖基化终末产物(AGE)的积累。然而，一个 在骨量高峰期，内分泌功能紊乱的风险可能比T1D更大的社区 应计是变性人和非二进制青年(TNB)。TNB中促性腺激素释放激素激动剂(GnRHa)的青春期阻断可以 防止睾酮增加骨小梁密度和大小，防止雌激素增加皮质骨 骨密度。已知双能X射线骨密度仪(DXA)测定的骨密度(BMD)为 TNb减少，特别是使用GnRHa后。然而，几乎没有关于体积大小的数据， GnRHa不影响TNB的骨量、强度和周转率。 在TNb中加上GnRHa或T1d的附加侮辱。本增刊的目的是扩大我们的 正在进行的T1D和对照儿童研究包括青春期前和青春期期间的不同性别青年 在有无T1D的情况下，使用体积、微结构和骨转换分析来探索 性别多样性、青春期独立和联合内分泌紊乱对骨获得的影响 封锁和T1D。我们的假设是，将我们的队列扩大到包括TNB可以使TNB骨骼的研究成为可能 健康，有和没有T1D。我们进一步假设，我们观察到的优先小梁赤字 合并高血糖的T1D在TNB中会加重，尤其是GnRHa的使用。为了实现总的目标， 我们将比较骨几何、微架构、骨小梁形态、微有限元分析(µFE)- 患有和不患有T1D的TNB青年的衍生骨强度和骨转换。在30个TNB(10个T1D，20个非T1D)之前 或者在青春期阻断期间，在跨性激素治疗之前，我们将进行一次相同的测量 对父母的研究：Tanner分期，骨龄；骨大小，面BMD和体成分DXA； 用HRpQCT测量骨密度、骨小梁和皮质骨的微结构和微细骨密度 通过个体小梁分割(ITS)的形态；通过形成和吸收以及性别的标记进行的周转 生物化学导致的类固醇；HbA1c和CGM引起的血糖升高；皮肤自发荧光引起的AGE积聚。我们 期待这些探索性数据为未来前瞻性临床试验的开发和实施提供信息 对于具有TNB独特健康关怀的T1D以及没有T1D的TNB，自启动 GnRHa通过跨性激素治疗。这将为降低T1D未来的骨折风险奠定基础 与TNB的差异，以及在没有T1D的TNB中，并改善终身骨健康结果。

Adolescence is a critical window for building bone and interrupting endocrine function during puberty jeopardizes peak bone mass accrual. In our parent study, we are finding that children with type 1 diabetes (T1D) have altered bone structure at the start of peak bone accrual as compared to matched controls. Our preliminary data show that trabecular area by high resolution peripheral quantitative CT (HRpQCT) is decreased in T1D. This deficit is associated with worse glycemia, including higher time in hyperglycemia by continuous glucose monitoring (CGM) and increased advanced glycation endproduct (AGE) accumulation by skin autofluorescence (SAF). Yet a community that is likely at even greater risk than T1D for disrupted endocrine function during peak bone mass accrual is transgender and nonbinary youth (TNB). Pubertal blockade by a GnRH agonist (GnRHa) in TNB can prevent testosterone from increasing trabecular bone density and size and estrogen from increasing cortical bone density. It is known that bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is decreased in TNB, especially with GnRHa use. However, there are almost no data about how volumetric, compartment-specific microarchitectural bone accrual, strength and turnover are affected in TNB not on GnRHa, and in TNB with the additional insults of GnRHa or T1D. The objective of this supplement is to expand our ongoing study of T1D and control children to include gender diverse youth both before and during pubertal blockade, with and without T1D, using volumetric, microarchitectural and bone turnover analysis to explore the impact on bone acquisition of the independent and combined endocrine disruptions of gender diversity, pubertal blockade and T1D. Our hypothesis is that expanding our cohort to include TNB enables the study of TNB skeletal health, with and without T1D. We further hypothesize that the preferential trabecular deficit that we observed in T1D with hyperglycemia will be exacerbated in TNB, especially with GnRHa use. To attain the overall objective, we will compare bone geometry, microarchitecture, trabecular morphology, microfinite element analysis (µFE)- derived bone strength and turnover in TNB youth with and without T1D. In 30 TNB (10 T1D, 20 non-T1D) before or during pubertal blockade, prior to cross-sex hormone treatment, we will perform once identical measurements to the parent study: Tanner stage, bone age; bone size, areal BMD and body composition by DXA; volumetric BMD, trabecular and cortical microarchitecture and µFE-derived bone strength by HRpQCT; trabecular morphology by individual trabecula segmentation (ITS); turnover by markers of formation and resorption and sex steroids by biochemistries; glycemia by HbA1c and CGM, and AGE accumulation by skin autofluorescence. We expect these exploratory data to inform the development and implementation of future prospective clinical trials of bone health for T1D with the unique health concern of TNB, as well as for TNB without T1D, from initiation of GnRHa through cross-sex hormone treatment. This will set the stage for mitigating future fracture risk in T1D with the disparity of TNB, as well as in TNB without T1D, and improving lifelong bone health outcomes.