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患有长期1型糖尿病的青少年骨量较低,反映骨吸收改变的骨指标水平也有所降低。

Adolescents with long-duration type 1 diabetes have low bone mass and reduced levels of bone indices reflecting altered bone resorption.

作者信息

Swolin-Eide Diana, Pundziute Lyckå Auste, Novak Daniel, Andersson Björn, Forsander Gun, Magnusson Per

机构信息

Department of Paediatrics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Queen Silvia Children's Hospital, Department of Paediatrics, Gothenburg, Sweden.

Bioinformatics and Data Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

Bone. 2025 Oct;199:117560. doi: 10.1016/j.bone.2025.117560. Epub 2025 Jun 4.

Abstract

The prevalence of type 1 diabetes (T1D) is increasing globally and is associated with severe complications, including an increased risk of fractures. This case-control study investigated whether young individuals with well-controlled, long-duration T1D have differences in bone mass and bone biomarkers in comparison with healthy matched controls. Fifty individuals, aged 15.0-17.9 years, with a T1D duration of at least 8 years and (mean ± SD) 10.6 ± 2.1 years were included, hence the participants had diabetes throughout most part of their puberty and growth spurt. The mean HbA1c since diabetes diagnosis was 56 ± 6 mmol/mol (7.3 ± 0.6 %). Bone mass was assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT). Clinical follow-up data were retrieved from the Swedish National Diabetes Registry. The control group comprised 50 healthy matched adolescents, aged 15.1-17.9 years. The groups were well-matched with no significant differences in age, sex, weight, height, body mass index and the self-reported physical activity. Total body less head aBMD and Z-scores were significantly lower in T1D individuals, p < 0.05. Total tibia density and trabecular density, by pQCT, were also lower in the T1D group, p < 0.05. There were no differences between the groups for parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase (BALP), intact procollagen type I N-propeptide (PINP), sclerostin, bioactive sclerostin and osteoprotegerin. However, individuals with T1D had reduced levels of C-terminal telopeptide of type I collagen (CTX) (p < 0.001) and nuclear factor κB ligand (a.k.a. RANKL) (p = 0.01), indicating altered regulation of osteoclasts. In conclusion, young individuals with well-controlled, long-duration T1D have subnormal bone mass accrual, impaired microstructure at several sites and suppressed RANKL-mediated osteoclastogenesis resulting in reduced bone resorption. Based on these findings, we suggest that bone health should be monitored in pediatric diabetes care to potentially intervene early in life in susceptible individuals to achieve optimal peak bone mass.

摘要

1型糖尿病(T1D)在全球范围内的患病率正在上升,并且与包括骨折风险增加在内的严重并发症相关。这项病例对照研究调查了长期T1D病情控制良好的年轻个体与健康匹配对照相比,在骨量和骨生物标志物方面是否存在差异。纳入了50名年龄在15.0 - 17.9岁之间、T1D病程至少8年且(均值±标准差)为10.6±2.1年的个体,因此这些参与者在青春期和生长突增的大部分时间里都患有糖尿病。自糖尿病诊断以来的平均糖化血红蛋白(HbA1c)为56±6 mmol/mol(7.3±0.6%)。通过双能X线吸收法和外周定量计算机断层扫描(pQCT)评估骨量。从瑞典国家糖尿病登记处获取临床随访数据。对照组包括50名年龄在15.1 - 17.9岁之间的健康匹配青少年。两组在年龄、性别、体重、身高、体重指数和自我报告的身体活动方面匹配良好,无显著差异。T1D个体的全身除头部骨密度(aBMD)和Z值显著较低,p<0.05。通过pQCT测量,T1D组的胫骨总密度和小梁密度也较低,p<0.05。两组在甲状旁腺激素、25 - 羟基维生素D、骨特异性碱性磷酸酶(BALP)、I型原胶原N端前肽(PINP)、硬化蛋白、生物活性硬化蛋白和骨保护素方面无差异。然而,T1D个体的I型胶原C端肽(CTX)水平降低(p<0.001),核因子κB配体(又名RANKL)水平降低(p = 0.01),表明破骨细胞的调节发生改变。总之,长期T1D病情控制良好的年轻个体骨量积累低于正常水平,多个部位的微观结构受损,RANKL介导的破骨细胞生成受到抑制,导致骨吸收减少。基于这些发现,我们建议在儿科糖尿病护理中监测骨骼健康,以便在生命早期对易感个体进行潜在干预,以实现最佳的峰值骨量。

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