Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications among Individuals with Type 2 Diabetes: A Prospective Study

Liangkai Chen,Qi Lu,Xue Chen,Sen Liu,Tingting Geng,Xiaoyu Lin,Gang Liu,Joann E Manson,Zhenzhen Wan,An Pan,Zhilei Shan,Liegang Liu,Kai Zhu,Yanjun Guo,Rui Li

doi:10.2337/figshare.20427807.v1

Abstract

Objectives: Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. This study aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with the risk of diabetic microvascular complications. Research Design and Methods: This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications were ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The median (interquartile range) of serum 25(OH)D concentration was 40.7 (27.5, 56.4) nmol/L. During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR (95% CI) of 0.65 (0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, compared with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs (95% CIs) of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. Conclusions: Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.

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