Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus

BackgroundDiabetic retinopathy (DR), one of the most common microvascular complications of diabetes mellitus (DM), remains to be a major driver of vision loss worldwide. Vitamin D has been reported to be involved in DR pathogenesis, but results have been inconsistent. We aimed to explore the relatio...

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Main Authors: Jing He, Jingrui Kang, Zhou Mei, Xiaohui Zhou, Yingchuan Yin, Cuiling Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1541961/full
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author Jing He
Jingrui Kang
Zhou Mei
Xiaohui Zhou
Yingchuan Yin
Cuiling Zhu
author_facet Jing He
Jingrui Kang
Zhou Mei
Xiaohui Zhou
Yingchuan Yin
Cuiling Zhu
author_sort Jing He
collection DOAJ
description BackgroundDiabetic retinopathy (DR), one of the most common microvascular complications of diabetes mellitus (DM), remains to be a major driver of vision loss worldwide. Vitamin D has been reported to be involved in DR pathogenesis, but results have been inconsistent. We aimed to explore the relationship between blood 25-hydroxyvitamin D, 25(OH)D, level and the risk of DR in patients with type 2 diabetes (T2DM).MethodsA total of 535 adults with T2DM from our department were included. Demographic information, biochemical data, 25(OH)D, and sex hormones were collected. Fundus photography was performed to determine the presence of DR. Participants were grouped into the DR group and the non-DR (NDR) group according to the fundus examinations and four groups based on serum 25(OH)D levels as follows: normal, insufficient, deficient, and severely deficient. Multivariate logistic regression analysis was used to evaluate the association between 25(OH)D and risk of DR.ResultsMales but not females with DR had significantly decreased levels of 25(OH)D (16.4 ± 5.6 ng/ml vs. 21.0 ± 5.0 ng/ml, P = 0.001) and increased proportion of severe 25(OH)D deficiency (14.8% vs. 6.7%, P = 0.022) compared to those without DR. Likewise, there was a gradually increasing percentage of DR with the reduction of 25(OH)D levels only in males (35.7%, 44.4%, 53.2%, 70.3%, P = 0.022). Intriguingly, total testosterone (TT) levels decreased markedly in males with DR (12.9 ± 5.2 nmol/L vs. 14.2 ± 5.5 nmol/L, P = 0.035) compared to their counterparts and correlated positively with 25(OH)D (β = 0.161, P = 0.007), which did not occur in females. After multivariate adjustment, we observed a significant inverse association between serum 25(OH)D and the occurrence of DR in males, showing that the adjusted ORs (AORs) and 95% confidence interval for DR were 0.233 (0.070–0.779) in the normal group, 0.280 (0.103–0.756) in the insufficient group, and 0.477 (0.196–1.164) in the deficiency group with the severely deficient group as a reference (P-trend = 0.003). However, such a significant association was not observed in females (P-trend = 0.137).ConclusionWe concluded a gender-specific relationship between serum 25(OH)D and the incidence of DR in T2DM, supported by a significant inverse association between serum 25(OH)D and DR only in males, which could be mediated by a marked reduction in TT levels.
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spelling doaj-art-b36c2982c53e49e7b6dc973b7c68ff6d2025-08-20T03:53:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15419611541961Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitusJing He0Jingrui Kang1Zhou Mei2Xiaohui Zhou3Yingchuan Yin4Cuiling Zhu5Department of Endocrinology, The Third People’s Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, Hefei, ChinaDepartment of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei, Hebei, ChinaDepartment of Endocrinology, The Third People’s Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, Hefei, ChinaDepartment of Endocrinology, The Third People’s Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, Hefei, ChinaDepartment of Endocrinology, The Third People’s Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, Hefei, ChinaDepartment of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Shanghai, ChinaBackgroundDiabetic retinopathy (DR), one of the most common microvascular complications of diabetes mellitus (DM), remains to be a major driver of vision loss worldwide. Vitamin D has been reported to be involved in DR pathogenesis, but results have been inconsistent. We aimed to explore the relationship between blood 25-hydroxyvitamin D, 25(OH)D, level and the risk of DR in patients with type 2 diabetes (T2DM).MethodsA total of 535 adults with T2DM from our department were included. Demographic information, biochemical data, 25(OH)D, and sex hormones were collected. Fundus photography was performed to determine the presence of DR. Participants were grouped into the DR group and the non-DR (NDR) group according to the fundus examinations and four groups based on serum 25(OH)D levels as follows: normal, insufficient, deficient, and severely deficient. Multivariate logistic regression analysis was used to evaluate the association between 25(OH)D and risk of DR.ResultsMales but not females with DR had significantly decreased levels of 25(OH)D (16.4 ± 5.6 ng/ml vs. 21.0 ± 5.0 ng/ml, P = 0.001) and increased proportion of severe 25(OH)D deficiency (14.8% vs. 6.7%, P = 0.022) compared to those without DR. Likewise, there was a gradually increasing percentage of DR with the reduction of 25(OH)D levels only in males (35.7%, 44.4%, 53.2%, 70.3%, P = 0.022). Intriguingly, total testosterone (TT) levels decreased markedly in males with DR (12.9 ± 5.2 nmol/L vs. 14.2 ± 5.5 nmol/L, P = 0.035) compared to their counterparts and correlated positively with 25(OH)D (β = 0.161, P = 0.007), which did not occur in females. After multivariate adjustment, we observed a significant inverse association between serum 25(OH)D and the occurrence of DR in males, showing that the adjusted ORs (AORs) and 95% confidence interval for DR were 0.233 (0.070–0.779) in the normal group, 0.280 (0.103–0.756) in the insufficient group, and 0.477 (0.196–1.164) in the deficiency group with the severely deficient group as a reference (P-trend = 0.003). However, such a significant association was not observed in females (P-trend = 0.137).ConclusionWe concluded a gender-specific relationship between serum 25(OH)D and the incidence of DR in T2DM, supported by a significant inverse association between serum 25(OH)D and DR only in males, which could be mediated by a marked reduction in TT levels.https://www.frontiersin.org/articles/10.3389/fendo.2025.1541961/fulltype 2 diabetesdiabetic retinopathy25-hydroxyvitamin Dtotal testosteronegender-specific difference
spellingShingle Jing He
Jingrui Kang
Zhou Mei
Xiaohui Zhou
Yingchuan Yin
Cuiling Zhu
Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
Frontiers in Endocrinology
type 2 diabetes
diabetic retinopathy
25-hydroxyvitamin D
total testosterone
gender-specific difference
title Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
title_full Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
title_fullStr Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
title_full_unstemmed Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
title_short Gender-specific association between circulating 25-hydroxyvitamin D levels and diabetic retinopathy in patients with type 2 diabetes mellitus
title_sort gender specific association between circulating 25 hydroxyvitamin d levels and diabetic retinopathy in patients with type 2 diabetes mellitus
topic type 2 diabetes
diabetic retinopathy
25-hydroxyvitamin D
total testosterone
gender-specific difference
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1541961/full
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