Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Department of Pediatrics, Division of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado.
Diabetes Obes Metab. 2019 Jun;21(6):1388-1398. doi: 10.1111/dom.13665. Epub 2019 Mar 28.
AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS: PUA was highest in patients with the longest T1D duration: 197 ± 44 μmol/L in adolescents versus 264 ± 82 μmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (β = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (β = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.
目的:研究在青少年、青年和老年人群中,广泛的 1 型糖尿病(T1D)病程范围内,正常血浆尿酸(PUA)水平与肾血流动力学功能、动脉僵硬度以及血浆肾素和醛固酮之间的关系。
材料与方法:在接受血糖钳夹试验的 T1D 患者中,测量了 PUA、肾小球滤过率(GFR)、有效肾血浆流量(ERPF)、血管僵硬度参数(主动脉增强指数[AIx]、颈动脉 AIx、颈动脉-股动脉脉搏波速度[cfPWV])以及血浆肾素和醛固酮的水平:27 名青少年(平均年龄±标准差为 16.8±1.9 岁)、52 名青年(平均年龄±标准差为 25.6±5.5 岁)和 66 名老年人(平均年龄±标准差为 65.7±7.5 岁)。
结果:在 T1D 病程最长的患者中,PUA 水平最高:青少年为 197±44 μmol/L,老年人为 264±82 μmol/L(P<0.001)。即使在校正年龄、糖化血红蛋白和性别后,高 PUA 仅与老年人的 GFR 降低相关(β=-2.12±0.56;P=0.0003),但与青少年或青年人无关。高 PUA 与青少年的颈动脉 AIx 降低相关(β=-1.90,P=0.02)。相比之下,在 T1D 老年人中,高 PUA 与 cfPWV 升高(P=0.02)和血浆肾素升高(P=0.01)相关。
结论:仅在长期 T1D 的老年患者中观察到高 PUA 与 GFR 降低、动脉僵硬度增加以及肾素-血管紧张素-醛固酮系统(RAAS)激活之间的关系。T1D 病程可能会改变 PUA、肾血流动力学功能和 RAAS 激活之间的关联,导致肾血管收缩和缺血。进一步的研究必须确定降低 PUA 的药物治疗是否可以预防或逆转长期 T1D 的有害血流动力学和神经激素后果,从而改善临床结局。
Diabetes Obes Metab. 2019-3-28
Nephrology (Carlton). 2019-9-12
Am J Kidney Dis. 2019-2-22
Am J Physiol Renal Physiol. 2014-11-5
J Clin Hypertens (Greenwich). 2025-1
J Clin Endocrinol Metab. 2024-1-18
Int J Biol Sci. 2023
Front Pediatr. 2021-6-15
Diabetologia. 2021-6
Biomed Res Int. 2020
JCI Insight. 2018-1-11
Am J Physiol Renal Physiol. 2017-6-1
Can J Diabetes. 2015-1-16
Am J Physiol Renal Physiol. 2014-11-5