Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes.
Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes.
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DOI：
10.1002/jbmr.4466
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Schwartz AV
中科院分区：
文献类型：
--
作者：
Dhaliwal R;Ewing SK;Vashishth D;Semba RD;Schwartz AV
晚期糖基化终末产物 (AGE) 在骨骼中的积累会改变胶原蛋白的结构和功能。荧光 AGE 与骨折相关，但对于非荧光 AGE 知之甚少。我们在老年人的健康、衰老和身体成分队列中检查了羧甲基赖氨酸 (CML) 与 2 型糖尿病 (T2D) 状态的临床和流行椎体骨折之间的关联。评估临床骨折事件和基线椎骨骨折。使用 Cox 回归分析血清 CML 与临床骨折发生率之间的关联，并使用 Logistic 回归分析椎体骨折发生率。基线时，T2D (n = 712) 和非糖尿病 (n = 2332) 患者的平均±标准差 (SD) 年龄分别为 73.7 ± 2.8 岁和 73.6 ± 2.9 岁。 T2D 患者的基线 CML 水平高于非糖尿病患者（893 ± 332 与 771 ± 270 ng/mL，p < 0.0001）。在多变量模型中，较高的 CML 与 T2D 患者发生临床骨折的较高风险相关（风险比 [HR] 1.49；95% 置信区间 [CI]，CML 每增加 1-SD，1.24–1.79），但在非糖尿病患者中则不然（HR 1.03；95% CI，0.94–1.13；交互作用 p = 0.001）。这种关联与骨矿物质密度 (BMD)、糖化血红蛋白（A1c 血红蛋白）、体重、体重减轻、吸烟、胱抑素 C 和药物使用无关。在两组中，CML 与椎体骨折的发生率均无显着相关性。总之，较高的 CML 水平与 T2D 发生临床骨折的风险增加相关，与 BMD 无关。这些结果表明 CML 与糖尿病骨脆性的发病机制有关。
Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24–1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94–1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes.
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