2型糖尿病非裔美国人的血浆成纤维细胞生长因子23与动脉粥样硬化钙化斑块
Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus.
作者信息
Freedman Barry I, Divers Jasmin, Russell Gregory B, Palmer Nicholette D, Bowden Donald W, Carr J Jeffrey, Wagenknecht Lynne E, Hightower R Caresse, Xu Jianzhao, Smith Susan Carrie, Langefeld Carl D, Hruska Keith A, Register Thomas C
机构信息
Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, N.C., USA.
出版信息
Am J Nephrol. 2015;42(6):391-401. doi: 10.1159/000443241. Epub 2015 Dec 23.
BACKGROUND
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial.
METHODS
Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate.
RESULTS
The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up.
CONCLUSIONS
Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.
背景
成纤维细胞生长因子23（FGF23）是一种磷尿激素，与血清磷浓度和维生素D紊乱有关。FGF23在血管钙化中的作用仍存在争议。
方法
在非裔美国人糖尿病心脏研究参与者中，对545名患有2型糖尿病（T2D）且肾功能保留的非裔美国人，确定FGF23与冠状动脉钙化动脉粥样硬化斑块（CAC）、主髂动脉钙化斑块（CP）、颈动脉CP、体积骨密度（vBMD）、蛋白尿和估计肾小球滤过率（eGFR）之间的关系。采用广义线性模型来检验FGF23与心血管、骨骼和肾脏表型之间的关联，以及随时间测量值的变化，并对年龄、性别、非洲血统比例、体重指数、糖尿病病程、糖化血红蛋白、血压、肾素 - 血管紧张素系统抑制剂、他汀类药物、钙补充剂、血清钙和血清磷进行校正。
结果
样本中女性占56.7%，平均（标准差）年龄为55.6（9.6）岁，糖尿病病程为10.3（8.2）年，eGFR为90.9（22.1）ml/min/1.73 m²，尿白蛋白：肌酐比值（UACR）为151（588）（中位数13）mg/g，血浆FGF23为161（157）RU/ml，CAC为637（1179）mg。在完全校正模型中，FGF23与eGFR呈负相关（p < 0.0001），与UACR呈正相关（p < 0.0001），与CAC呈正相关（p = 0.0006），但与颈动脉CP或主动脉CP无关。在平均5.1年的随访后，基线FGF23浓度与vBMD或CAC的变化无关。
结论
在研究较少的患有T2D的非裔美国人人群中，血浆FGF23浓度与亚临床冠状动脉疾病、蛋白尿和肾功能独立相关。研究结果支持FGF23与血管钙化之间的关系，但不支持FGF23与骨密度之间的关系，在缺乏晚期肾病的非裔美国人中。
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