PDF(Pubmed)
Abstract：
Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D (n = 48, age 38 ± 4 years) and a healthy control group (n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls (p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = -0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria.
摘要：
糖尿病性神经病变和肾病是1型糖尿病（T1D）的常见并发症。症状在早期往往难以捉摸，和可用的诊断方法可以使用生物标志物进行改进。已在肾脏中鉴定出基质金属蛋白酶3（MMP-3），并被认为与糖尿病肾病有关。生长分化因子15（GDF-15）已被认为在糖尿病中具有积极作用，但与心血管风险等不良反应相关，肾功能下降，和神经变性。本研究旨在探讨血浆MMP-3和GDF-15作为T1D中糖尿病神经病变和肾病的系统性生物标志物。该研究涉及儿童期发病的T1D患者（n=48，年龄38±4岁）和健康对照组（n=30，年龄38±5岁）。神经生理学测试,白蛋白尿的评估，并进行了常规生化标志物的测量。神经病变损害评估（NIA）评分系统，在评估诸如感觉丧失和反射减弱等因素的地方，用于筛查神经病的症状。使用ELISA试剂盒测定肝素化血浆中的MMP-3和GDF-15浓度。总的来说,9例（19%）有蛋白尿，和25（52％）有糖尿病神经病变。各组间MMP-3浓度无显著差异。T1D中GDF-15水平较高，T1D的中位数和四分位数间距（IQR）为358（242）pg/mL，对照组为295（59）（p<0.001）。在合并的患者组中，MMP-3与血浆肌酐呈正相关,发现MMP-3与估计的肾小球滤过率之间呈负相关（eGFR;rho=-0.358，p=0.012），GDF-15与NIA（rho=0.723，p<0.001）和高敏C反应蛋白（rho=0.395，p=0.005）呈正相关。MMP-3在大量白蛋白尿中升高，仅在9例有白蛋白尿的T1D患者中与NIA呈正相关（rho=0.836，p=0.005）。本研究表明，高MMP-3与低eGFR有关，高血浆肌酐,和大量白蛋白尿，并且GDF-15可以是T1D中糖尿病性神经病变的生物标志物。MMP-3可能是T1D伴蛋白尿神经病变的生物标志物。
