Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
Diabetes Metab J. 2021 May;45(3):349-357. doi: 10.4093/dmj.2019.0211. Epub 2021 Feb 2.
Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy.
This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimate the severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed.
The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV.
This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.
心血管自主神经病变（CAN）是糖尿病的一种常见微血管并发症，与糖尿病肾病（DN）中的白蛋白尿有关。尿 N-乙酰-β-D-氨基葡萄糖苷酶（uNAG）是一种肾小管损伤标志物，已被报道为 DN 的早期标志物，甚至在白蛋白正常的患者中也是如此。本研究评估了 uNAG 是否与无肾病的 1 型糖尿病（T1DM）患者中 CAN 的存在和严重程度相关。
这项横断面研究纳入了 247 例无慢性肾脏病和白蛋白尿的 T1DM 患者，他们在 3 个月内同时进行了 uNAG 和自主功能测试。CAN 的存在通过四项自主功能测试的年龄依赖性参考值进行评估。总 CAN 评分是五个心血管反射测试的部分分数之和，用于评估 CAN 的严重程度。分析了 uNAG 与心率变异性（HRV）参数之间的相关性。
在多变量逻辑回归模型中，log-uNAG 与 CAN 的存在呈显著相关（调整后的优势比，2.39；95%置信区间[CI]，1.08 至 5.28；P=0.031）。在多变量线性回归模型中，总 CAN 评分与 loguNAG 呈正相关（β=0.261，P=0.026）。log-uNAG 与 HRV 的频域和时域指数呈负相关。
本研究验证了 uNAG 与无肾病的 T1DM 患者中 CAN 的存在和严重程度以及 HRV 变化之间的关联。uNAG 的潜在作用应在无肾病的 T1DM 患者中进一步评估高危 CAN 患者。
