Aims/hypothesis

As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.

Methods

The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA_1c 5.7–6.4% [39–47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.

Results

In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=−0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=−0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.

Conclusions/interpretation

An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

Graphical Abstract

中文翻译：

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葡萄糖耐量和胰岛素抵抗/敏感性与视网膜层特征相关：LIFE-Adult-Study

目标/假设

随着世界各地胰岛素抵抗和葡萄糖不耐受的患病率不断增加，糖尿病引起的眼病成为全球健康负担。我们的目标是在基于人群的大型数据集中使用非侵入性高分辨率谱域光学相干断层扫描（SD-OCT）来识别与胰岛素和葡萄糖代谢密切相关的不同光带。

方法

LIFE-成人研究从德国莱比锡人口登记处随机挑选了 10,000 名参与者。横断面标准化表型分析包括对各种代谢风险标记物和眼部成像的评估，例如 SD-OCT 得出的视网膜 10 个光带的厚度。全球和早期治疗糖尿病视网膜病变研究 (ETDRS) 对来自 LIFE-成人研究的 7384 名参与者的 7384 只健康眼睛的亚场特异性光学视网膜层厚度进行了研究，按正常糖耐量、糖尿病前期（空腹血糖受损和/或糖耐量受损）进行分层和/或 HbA _1c 5.7–6.4% [39–47 mmol/mol]）和糖尿病。视网膜光学带特征与不同糖耐量指数（例如空腹血糖、血糖曲线下面积）、胰岛素抵抗（例如 HOMA2-IR、甘油三酯葡萄糖指数）或胰岛素敏感性（例如估计的葡萄糖处理率 [eGDR]）的关联、Stumvoll 代谢清除率）是使用针对年龄、性别和屈光度进行调整的个体标记物的多变量线性回归分析来确定的。进行了各种敏感性分析以验证观察到的结果。

结果

在研究队列中，视网膜的十个光学带中有九个在带厚度上显示出显着的性别和葡萄糖耐量依赖性差异。多变量线性回归分析揭示了葡萄糖耐受不良和胰岛素抵抗的标志物（例如HOMA2-IR）与代表解剖性视网膜外核层的光学带的厚度（ONL，标准化β =-0.096； HOMA2-IR 的p <0.001）和光感受器的肌样区（MZ；β =−0.096； HOMA2-IR p <0.001）。相反，胰岛素敏感性标志物（例如 eGDR）与 ONL（ β = 0.090；对于 eGDR， p <0.001）和 MZ（β = 0.133；对于 eGDR， p <0.001）带厚度呈正相关且独立相关。这些全球关联在 ETDRS 子领域特定分析中得到了证实。通过葡萄糖稳态对队列进行分层后，对体力活动、神经解剖细胞/组织类型和 ETDRS 子字段类别进行调查，敏感性分析进一步验证了我们的发现。

结论/解释

葡萄糖稳态受损与视网膜 ONL 和光感受器 MZ 的光带变薄有关。 ONL 和 MZ 厚度的变化可能预测糖尿病的早期代谢性视网膜改变。

图形概要