Tear Levels of IGFBP-3: A Potential Biomarker for Diabetic Nerve Changes in the Cornea.
Tear Levels of IGFBP-3: A Potential Biomarker for Diabetic Nerve Changes in the Cornea.
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DOI：
10.1097/icl.0000000000000700
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Robertson DM
中科院分区：
文献类型：
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作者：
Stuard WL;Titone R;Robertson DM
2型糖尿病在美国和世界范围内已达到流行水平。这种疾病的眼部并发症包括糖尿病视网膜病变和角膜病变，两者都可导致严重的视力丧失。糖尿病性角膜病变与疼痛性眼表疾病有关，包括角膜糜烂和伤口愈合延迟。我们实验室最近的工作主要集中在胰岛素样生长因子（IGF）系统在糖尿病角膜疾病中的作用。在这里，我们回顾了最近关于人泪液中存在的IGF-1、胰岛素和胰岛素样结合蛋白（IGFBP-3）的发现，并评估了它们作为糖尿病生物标志物的潜在用途。我们进一步使用体内共聚焦显微镜作为糖尿病重要的成像生物标志物来检验临床证据，并讨论糖尿病患者泪膜变化与角膜神经丧失之间的关系。IGFBP-3是唯一与2型糖尿病患者神经丧失显著相关的泪膜标志物，而IGF-1的泪膜水平与衰老相关。有趣的是，IGFBP-3的泪液水平与血清HbA1c水平没有直接关系，这表明高血糖本身并不会导致该蛋白的分泌增加。大量证据支持使用体内共聚焦显微镜作为评估研究环境中糖尿病引起的角膜神经和上皮变化的工具。新发现的糖尿病患者角膜基底下神经丛形态学变化与IGFBP-3泪液水平升高之间的关系表明，该蛋白可能是评估2型糖尿病眼部和非眼部并发症风险的一种创新的新生物标志物。
Type 2 diabetes mellitus has reached epidemic levels in the U.S. and worldwide. Ocular complications from this disease include diabetic retinopathy and keratopathy, both of which can lead to significant vision loss. While frequently underappreciated, diabetic keratopathy is associated with painful ocular surface disorders, including corneal erosions and delayed wound healing. Recent work in our laboratory has focused on the role of the insulin-like growth factor (IGF) system in diabetic corneal disease. Here we review recent findings on the presence of IGF-1, insulin, and the insulin-like binding protein (IGFBP-3) in human tear fluid and evaluate their potential use as biomarkers in diabetes. We further examine clinical evidence using in vivo confocal microscopy as an important imaging biomarker in diabetes and discuss associations between tear film changes in diabetes and corneal nerve loss. IGFBP-3 was the only tear film marker significantly associated with nerve loss in Type 2 diabetes, whereas tear levels of IGF-1 were associated with aging. Interestingly, tear levels of IGFBP-3 were not directly related to serum levels of HbA1c, suggesting that hyperglycemia alone is not driving increased secretion of this protein. Overwhelming evidence supports the use of in vivo confocal microscopy as a tool to evaluate corneal nerve and epithelial changes induced by diabetes in research settings. The newly identified relationship between morphological changes in the corneal subbasal nerve plexus in diabetes and the increase in tear levels of IGFBP-3 suggest that this protein may represent an innovative new biomarker to assess risk for ocular and non-ocular complications in Type 2 diabetes mellitus.