Raisingani Manish, Preneet Brar, Kohn Brenda, Yakar Shoshana
Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, New York University School of Medicine, New York, NY 10016, United States.
David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010-4086, United States.
Growth Horm IGF Res. 2017 Jun;34:13-21. doi: 10.1016/j.ghir.2017.04.003. Epub 2017 Apr 28.
Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM.
1型糖尿病（T1DM）是儿童期最常见的慢性病之一。儿童期和青少年期也是身高增长和骨骼骨矿物质密度（BMD）获取的最重要时期。调节生长的生长激素（GH）/胰岛素样生长因子-1（IGF-1）轴受T1DM影响，研究表明T1DM患儿的GH水平升高而IGF-1水平降低。关于TIDM青少年是否能够达到其遗传决定的成人身高，存在相互矛盾的数据。此外，数据支持T1DM青少年的峰值骨密度降低，尽管其病理生理学尚未完全明确。已经提出了多种导致骨密度降低的机制，包括骨钙素水平低，反映骨形成减少；硬化蛋白增加，骨合成代谢途径的抑制剂；以及瘦素增加，一种通过中枢和外周机制影响骨代谢的脂肪细胞因子。与T1DM中骨吸收增加有关的其他因素包括骨保护素/核因子-κB配体受体激活途径的上调、甲状旁腺激素水平升高以及参与慢性全身炎症的其他细胞因子激活。在本综述中，我们总结了针对T1DM儿童和青少年GH/IGF-I轴、线性生长速度和骨密度改变的临床研究；并回顾了可能导致T1DM儿童和青少年线性生长减弱和峰值骨量获取减少的分子机制。
