Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study

Yanqi Fu; Meng Lu; Kun Zhang; Ying Sun; Xiao Tan; Ningjian Wang; Fei Xu; Boren Jiang; Yingli Lu; Bin Wang

doi:10.1210/clinem/dgae221

Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study

J Clin Endocrinol Metab. 2024 Apr 4:dgae221. doi: 10.1210/clinem/dgae221. Online ahead of print.

Authors

Yanqi Fu¹, Meng Lu², Kun Zhang¹, Ying Sun¹, Xiao Tan^{3

4}, Ningjian Wang¹, Fei Xu⁵, Boren Jiang¹, Yingli Lu¹, Bin Wang¹

Affiliations

¹ Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Research Center for Clinical Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁴ Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
⁵ iHuman Institute, School of Life Science and Technology, Shanghai Tech University, Shanghai, China.

PMID: 38571313
DOI: 10.1210/clinem/dgae221

Abstract

Context: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status.

Objective: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR).

Methods: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs.

Results: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes.

Conclusions: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

Keywords: Gene polymorphisms; Glycemic spectrum; Prediabetes; Type 2 diabetes; Vitamin D; Vitamin D receptor.

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