Background

Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes.

Methods

This cross-sectional study was embedded in a long-term observational study, the Epidemiology of Diabetes Interventions and Complications study (EDIC), a cohort of participants with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and Canada. All active EDIC participants were eligible except if they were pregnant, weighed above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator, or were not willing to participate. The primary study outcome was total hip BMD. Hip, spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an annual EDIC visit (2017–19). Time-weighted mean HbA_1c, kidney disease, and peripheral neuropathy were measured annually during EDIC, and retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed once (2009–10) during EDIC.

Findings

1147 of the 1441 participants who were enrolled in the DCCT trial remained active EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017, and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health study. 1058 participants completed at least one of a set of DXA scans and were included in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7). Higher mean HbA_1c, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy) were independently associated with a lower total hip BMD. Total hip BMD differed by –10·7 mg/cm² (95% CI –19·6 to –1·7) for each 1% increase in mean HbA_1c, –20·5 mg/cm² (–29·9 to –11·0) for each 5 unit higher skin intrinsic fluorescence, and –51·7 mg/cm² (–80·6 to –22·7) in the presence of kidney disease. Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS.

Interpretation

Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic control and prevention of kidney disease might reduce bone loss and ultimately fractures in this population. Osteoporosis screening might be particularly important in people with these risk factors. Further research to identify AGE blockers could benefit skeletal health.

Funding

National Institute of Diabetes and Digestive and Kidney Disease

中文翻译：

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1 型糖尿病老年人骨密度降低的危险因素：一项横断面研究

背景

1 型糖尿病与较低的骨密度 (BMD) 和骨折风险增加有关，但关于糖尿病相关因素对 BMD 的影响知之甚少。我们评估了这些因素是否与患有 1 型糖尿病的老年患者的髋部 BMD 较低有关。

方法

这项横断面研究嵌入了一项长期观察性研究，即糖尿病干预和并发症流行病学研究 (EDIC)，这是一组 1 型糖尿病参与者，他们最初参加了糖尿病控制和并发症试验 (DCCT) ，并在美国和加拿大的 27 个地点进行了 30 多年的随访。所有活跃的 EDIC 参与者都有资格，除非他们怀孕、体重超过双能 X 射线吸收测定法 (DXA) 扫描仪限制、植入了神经刺激器或不愿意参与。主要研究结果是全髋 BMD。在每年一次的 EDIC 访问（2017-19）中，使用 DXA 测量了髋关节、脊柱和桡骨的 BMD 和骨小梁评分 (TBS)。时间加权平均 HbA _1c、肾脏疾病和周围神经病变在 EDIC 期间每年测量一次，视网膜病变每 4 年测量一次。在 EDIC 期间（2009-10 年）对皮肤固有荧光、晚期糖基化终末产物 (AGEs) 和心脏自主神经病变进行了一次评估。

发现

参加 DCCT 试验的 1441 名参与者中有 1147 名在这项横断面研究开始时仍然是活跃的 EDIC 参与者。2017 年 9 月 20 日至 2019 年 9 月 19 日期间，1147 名参与者中的 1094 名接受了 EDIC 骨骼健康研究的筛选。1058 名参与者至少完成了一组 DXA 扫描中的一个，并被纳入分析。47·8% 是女性，52·2% 是男性，96·6% 是白人，3·4% 是其他种族。参与者的平均年龄为 59·2 岁 (SD 6·7)。较高的平均 HbA _1c、较高的皮肤固有荧光和肾脏疾病（但不是视网膜病变或神经病变）与较低的全髋 BMD 独立相关。_{平均 HbA 1c}每增加 1%，全髋 BMD 相差 –10·7 mg/cm ^{2 （95% CI –19·6 至 –1·7）}, –20·5 mg/cm ² (–29·9 to –11·0) 每 5 个单位更高的皮肤固有荧光, –51·7 mg/cm ² (–80·6 to –22·7) in肾脏疾病的存在。股骨颈和超远端桡骨 BMD 也有类似关联，但腰椎 BMD 或 TBS 则没有。

解释

较差的血糖控制、AGE 积累和肾脏疾病是患有 1 型糖尿病的老年人髋部 BMD 较低的独立危险因素。维持血糖控制和预防肾脏疾病可能会减少该人群的骨质流失和最终骨折。骨质疏松症筛查对于有这些风险因素的人来说可能尤为重要。进一步研究以确定 AGE 阻滞剂可能有益于骨骼健康。

资金

国家糖尿病、消化和肾脏疾病研究所