Genetically mimicked effects of thyroid dysfunction on diabetic retinopathy risk: a 2-sample univariable and multivariable Mendelian randomization study.

Junlin Ouyang, Ling Zhou, Qing Wang, Wei Yan

Journal: Frontiers in endocrinology 2024;15():1374254

PMID: 39497807

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Plain Language Summary

Diabetic retinopathy (DR) is a common complication of diabetes, leading to vision impairment and blindness. Thyroid dysfunction (TD) has been suggested to influence the risk of developing DR, but the causal relationship remains unclear. The primary aim of this study was to determine whether genetically predicted TD influences the risk of diabetic retinopathy. This study was a Mendelian randomisation study based on the latest genome-wide association studies from the FinnGen database. Results showed a significant correlation between TD and diabetic retinopathy, with a particularly strong association for HPT. Authors concluded that genetically predicted TD, particularly hypothyroidism (HPT), can increase the risk of diabetes, thus highlighting the importance of monitoring thyroid function in patients with diabetes to mitigate the risk of developing DR.

Abstract

BACKGROUND

Thyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy.

METHODS

Using data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings.

RESULTS

In UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10-1.19; P<0.025). However, MVMR analysis, after adjusting for Graves' disease (GD) and/or rheumatoid arthritis (RA), revealed no significant association between TOS and the four stages of diabetic retinopathy. The Meta-analysis demonstrated the collective effect of TOS on diabetic retinopathy across all stages [OR=1.11; 95% CI (1.08-1.15); P<0.01]. In UVMR analysis, the estimates for hypothyroidism (HPT) and GD were similar to those for TOS. In the MVMR analysis, after adjusting for RA, the significant effect of HPT on DR and non-proliferative diabetic retinopathy (NPDR) remained. Additionally, MVMR analysis suggested that the estimates for GD on DR were not affected by TOS, except for GD-proliferative diabetic retinopathy (PDR). However, no significant correlation persisted after adjusting for RA, including for GD-PDR.

CONCLUSION

Our study demonstrated a significant association between thyroid dysfunction TD and DR, with the relationship being particularly pronounced in HPT-DR.

Address: China-Japan Union Hospital of Jilin University, Department of Endocrinology, Jilin, China.; China-Japan Union Hospital of Jilin University, Department of Obstetrics and Gynecology, Jilin, China.; China-Japan Union Hospital of Jilin University, Emergency Department, Jilin, China.

DOI: 10.3389/fendo.2024.1374254