尽管平均骨矿物质密度高得矛盾,但患有2型糖尿病的老年人骨折风险增加。这项研究确定了该高危人群中骨折风险的其他标志物。非酯化脂肪酸和氨基酸谷氨酰胺/谷氨酸和天冬酰胺/天冬氨酸与骨折相关。
目的:2型糖尿病(T2D)与骨折风险增加有关,尽管骨矿物质密度异常高。需要额外的骨折风险标志物来识别有风险的个体。
方法:MURDOCK研究是一项正在进行的研究,始于2007年,来自北卡罗来纳州中部的居民。在入学时,参与者完成健康问卷并提供生物样本.在此嵌套的案例控制分析中,成人T2D患者发生骨折,年龄≥50岁,通过自我报告和电子病历查询进行识别。骨折病例按年龄1:2匹配,性别,种族/民族,和BMI没有骨折的人。分析储存的血清的常规代谢物和靶向代谢组学(氨基酸和酰基肉碱)。使用条件逻辑回归评估了意外骨折和代谢特征之间的关联,控制多种混杂因素,包括烟草和酒精的使用,医疗合并症,和药物。
结果:发现107例骨折与210例匹配的对照。靶向代谢组学分析包括2个氨基酸因子,由以下组成:1)支链氨基酸,苯丙氨酸和酪氨酸;和2)谷氨酰胺/谷氨酸,天冬酰胺/天冬氨酸,精氨酸和丝氨酸[E/QD/NRS]。在控制了多种危险因素后,E/QD/NRS与骨折发生率显著相关(OR2.50,95%CI:1.36-4.63)。非酯化脂肪酸与较低的骨折几率相关(OR0.17,95%CI:0.03-0.87)。其他常规代谢物与骨折无关联,酰基肉碱因子,也不是其他氨基酸因素。
结论:我们的结果表明了新的生物标志物,并提出了潜在的机制,T2D老年人的骨折风险。
Older adults with type 2 diabetes mellitus have an increased risk of fracture despite a paradoxically higher average bone mineral density. This study identified additional markers of fracture risk in this at-risk population. Non-esterified fatty acids and the amino acids glutamine/glutamate and
asparagine/aspartate were associated with incident fractures.
OBJECTIVE: Type 2 diabetes mellitus (T2D) is associated with an increased risk of fracture despite a paradoxically higher bone mineral density. Additional markers of fracture risk are needed to identify at-risk individuals.
METHODS: The MURDOCK study is an ongoing study, initiated in 2007, of residents in central North Carolina. At enrollment, participants completed health questionnaires and provided biospecimen samples. In this nested
case-control analysis, incident fractures among adults with T2D, age ≥ 50 years, were identified by self-report and electronic medical record query. Fracture cases were matched 1:2 by age, gender, race/ethnicity, and BMI to those without incident fracture. Stored sera were analyzed for conventional metabolites and targeted metabolomics (amino acids and acylcarnitines). The association between incident fracture and metabolic profile was assessed using conditional logistic regression, controlled for multiple confounders including tobacco and alcohol use, medical comorbidities, and medications.
RESULTS: 107 incident fractures were identified with 210 matched controls. Targeted metabolomics analysis included 2 amino acid factors, consisting of: 1) the branched chain amino acids, phenylalanine and tyrosine; and 2) glutamine/glutamate,
asparagine/aspartate, arginine, and serine [E/QD/NRS]. After controlling for multiple risk factors, E/QD/NRS was significantly associated with incident fracture (OR 2.50, 95% CI: 1.36-4.63). Non-esterified fatty acids were associated with lower odds of fracture (OR 0.17, 95% CI: 0.03-0.87). There were no associations with fracture among other conventional metabolites, acylcarnitine factors, nor the other amino acid factors.
CONCLUSIONS: Our results indicate novel biomarkers, and suggest potential mechanisms, of fracture risk among older adults with T2D.