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The association of islet autoantibodies with the neural retinal thickness and microcirculation in type 1 diabetes mellitus with no clinical evidence of diabetic retinopathy

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Abstract

Objective

To examine the association between islet autoantibodies (IAbs) and the retinal neurovascular changes in type 1 diabetes mellitus (T1DM) with no diabetic retinopathy (NDR).

Methods

This cross-sectional study measured the neural retinal structure and microvascular density of 118 NDR eyes using spectral-domain optical coherence tomography angiography. Retinal structure parameters included retinal thickness (RT), inner retinal thickness (iRT), retina never fibral layer thickness (RNFL thickness), ganglion cell complex thickness (GCC thickness), and loss volume of GCC. Microvascular parameters included vessel density of superficial capillary plexus (sVD), vessel density of deep capillary plexus, and vessel density of choroid capillary plexus. Comparison and correlation analyses of these OCTA parameters were made with various IAbs, including glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase-related islet antigen 2 antibody (IA2A), and zinc transporter 8 antibody (ZnT8A). A general linear model was used to understand the association of IAbs with the retina parameters.

Results

The IAb positive (IAbs +) group, which included 85 patients, had thinner RT (235.20 ± 18.10 mm vs. 244.40 ± 19.90 mm at fovea, P = 0.021) and thinner iRT (120.10 ± 9.00 mm vs. 124.70 ± 6.90 mm at parafovea, P = 0.015), compared with the IAb negative (IAbs-) group comprising 33 patients. Furthermore, a more severe reduction of RT was demonstrated in the presence of multiple IAbs. Among the three IAbs, GADA was the most significant independent risk factor of all-round RT decrease (β = −0.20 vs. −0.27 at fovea and parafovea, respectively, P < 0.05), while titers of IA2A negatively affect sVD in the parafovea (β = −0.316, P = 0.003).

Conclusions

IAbs are associated with neural retinal thinning and microcirculation reduction in T1DM patients before the clinical onset of diabetic retinopathy.

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Abbreviations

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

IAbs:

Islet autoantibodies

ICA:

Islet cell antibody

GADA:

Glutamic acid decarboxylase antibody

IA2A:

Tyrosine phosphatase-related islet antigen 2 antibody

ZnT8A:

Zinc transporter 8 antibody

DR:

Diabetic retinopathy

NDR:

No clinical evidence of DR

BCVA:

Best-corrected visual acuity

SD-OCTA:

Spectral-domain optical coherence tomography angiography

VD:

Vascular density

ILM:

Inner limiting membrane

IPL:

Inner plexiform layer

RPE:

Retinal pigment epithelium

sVD:

Vessel density of superficial capillary plexus

dVD:

Vessel density of deep capillary plexus

cVD:

Vessel density of choroid capillary plexus

RT:

Retinal thickness

iRT:

Inner retinal thickness

RNFL:

Retina never fibral layer

GCC:

Ganglion cell complex

FLV:

Focal loss volume

GLV:

Global loss volume

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Acknowledgments

We thank Weihe Zhou (National Clinical Research Center for Ocular Diseases, Wenzhou, China) for their help and support with statistical analysis.

Funding

Our work was supported by the National Natural Science Foundation of China (No. 81072221), Projects of Research and Development in Key Areas of Hunan Province (No. 2017SK2020), and the Natural Science Foundation of Hunan Province (No. 2023JJ70017).

Author information

Author notes

  1. Tong Wang and Tong Zhang contribute to the article equally.

Authors and Affiliations

  1. Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Tong Wang, Ning Dong, Yao Tan, Liang Li, Yandan Zhou, Pu Zhang & Ling Gao

  2. National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xia Li, Yuting Xie & Ling Gao

  3. Department of Immunology, College of Basic Medical Immunology, Central South University, Changsha, 410011, China

    Ming Li

  4. School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Tong Zhang, Qianxin Li, Ronghan Wu & Ling Gao

  5. National Clinical Research Center for Ocular Diseases, Wenzhou, 325027, China

    Tong Zhang, Qianxin Li, Ronghan Wu & Ling Gao

  6. Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA, 94304, USA

    Liang Li

  7. Bourns Engineering, The University of California, Riverside, Riverside, CA, 92521, USA

    Ruixuan Wang

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Contributions

TW and TZ did the experiments and acquired, analyzed, and interpreted the data, and drafted and critically revised the manuscript. ND, YT, LL, YZ, PZ, QL, RW, and RW contributed to the fundus examination and collected the clinical data. YX and XL helped to organize the systemic examination for the DM coherent. ML critically revised the manuscript for important intellectual content. LG and RW contributed substantially to the conception and design, acquisition of data, or analysis and interpretation of data, and critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript. LG and RW were responsible for the integrity of the work as a whole.

Corresponding authors

Correspondence to Ronghan Wu or Ling Gao.

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We confirm that all our procedures involving human participants were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Communicated by Massimo Federici.

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Wang, T., Zhang, T., Dong, N. et al. The association of islet autoantibodies with the neural retinal thickness and microcirculation in type 1 diabetes mellitus with no clinical evidence of diabetic retinopathy. Acta Diabetol (2024). https://doi.org/10.1007/s00592-024-02255-8

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