Sherk Vanessa D, Vigers Timothy, Pyle Laura, Snell-Bergeon Janet K, Nadeau Kristen J, Rickels Michael R, Miller Kellee M, Greenbaum Carla J, Shah Viral N
Department of OrthopedicsSchool of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA.
Department of Biostatistics and Informatics Colorado School of Public Health University of Colorado Anschutz Medical Campus Aurora CO USA.
JBMR Plus. 2020 Aug 3;4(9):e10389. doi: 10.1002/jbm4.10389. eCollection 2020 Sep.
Type 1 diabetes (T1D) increases fracture risk across the lifespan. The low bone turnover associated with T1D is thought to be related to glycemic control, but it is unclear whether peripheral hyperinsulinemia due to dependence on exogenous insulin has an independent effect on suppressing bone turnover. The purpose of this study was to test the bone turnover marker (BTM) response to acute hyperinsulinemia. Fifty-eight adults aged 18 to 65 years with T1D over 2 years were enrolled at seven T1D Exchange Clinic Network sites. Participants had T1D diagnosis between age 6 months to 45 years. Participants were stratified based on their residual endogenous insulin secretion measured as peak C-peptide response to a mixed meal tolerance test. BTMs (CTX, P1NP, sclerostin [SCL], osteonectin [ON], alkaline phosphatase [ALP], osteocalcin [OCN], osteoprotegerin [OPG], osteopontin [OPN], and IGF-1) were assessed before and at the end of a 2-hour hyperinsulinemic-euglycemic clamp (HEC). Baseline ON ( = -0.30, = .022) and OCN ( = -0.41, = .002) were negatively correlated with age at T1D diagnosis, but baseline BTMs were not associated with HbA1c. During the HEC, P1NP decreased significantly (-14.5 ± 44.3%; = .020) from baseline. OCN, ON, and IGF-1 all significantly increased (16.0 ± 13.1%, 29.7 ± 31.7%, 34.1 ± 71.2%, respectively; all < .001) during the clamp. The increase in SCL was not significant (7.3 ± 32.9%, = .098), but the decrease in CTX (-12.4 ± 48.9, = .058) neared significance. ALP and OPG were not changed from baseline ( = .23 and = .77, respectively). Baseline ON and SCL were higher in men, but OPG was higher in women (all ≤ .029). SCL was the only BTM that changed differently in women than men. There were no differences in baseline BTMs or change in BTMs between C-peptide groups. Exogenous hyperinsulinemia acutely alters bone turnover, suggesting a need to determine whether strategies to promote healthy remodeling may protect bone quality in T1D. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
1型糖尿病（T1D）会增加全生命周期的骨折风险。与T1D相关的低骨转换被认为与血糖控制有关，但尚不清楚由于依赖外源性胰岛素导致的外周高胰岛素血症是否对抑制骨转换具有独立作用。本研究的目的是测试骨转换标志物（BTM）对急性高胰岛素血症的反应。在七个T1D交换诊所网络站点招募了58名年龄在18至65岁之间、患T1D超过2年的成年人。参与者在6个月至45岁之间被诊断为T1D。根据混合餐耐量试验中测得的残余内源性胰岛素分泌（以峰值C肽反应衡量）对参与者进行分层。在2小时高胰岛素-正常血糖钳夹（HEC）之前和结束时评估BTM（CTX、P1NP、骨硬化蛋白[SCL]、骨连接蛋白[ON]、碱性磷酸酶[ALP]、骨钙素[OCN]、骨保护素[OPG]、骨桥蛋白[OPN]和IGF-1）。基线ON（ = -0.30， = .022）和OCN（ = -0.41， = .002）与T1D诊断时的年龄呈负相关，但基线BTM与糖化血红蛋白（HbA1c）无关。在HEC期间，P1NP较基线显著下降（-14.5 ± 44.3%； = .020）。钳夹期间OCN、ON和IGF-1均显著增加（分别为16.0 ± 13.1%、29.7 ± 31.7%、34.1 ± 71.2%；均 < .001）。SCL的增加不显著（7.3 ± 32.9%， = .098），但CTX的下降（-12.4 ± 48.9， = .058）接近显著水平。ALP和OPG与基线相比无变化（分别为 = .23和 = .77）。男性的基线ON和SCL较高，但女性的OPG较高（均 ≤ .029）。SCL是唯一在女性和男性中变化不同的BTM。C肽组之间的基线BTM或BTM变化没有差异。外源性高胰岛素血症会急性改变骨转换，这表明需要确定促进健康重塑的策略是否可以保护T1D患者的骨质。© 2020美国骨与矿物质研究学会 © 2020作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
