Available online 27 April 2024, 109659

Author links open overlay panel, , , , , , , ABSTRACTObjective

Prediabetes is a crucial stage for prevention and treatment of diabetes, and vitamin D (VD) has been found to be linked to the development of prediabetes and diabetes. Thus, we aimed to identify the effect of VD supplementation on glucose metabolism in prediabetic participants and mice.

Design and Methods

A 1:1 paired design of randomized, placebo-controlled trial with 1600 IU/day VD3 or placebo was administered to individuals with prediabetes, two-way repeated-measures ANCOVA was used to analyze glycolipid and inflammatory factors. A high-fat diet induced prediabetic KKay mice were utilized to evaluate the effects of VD3 with 16 weeks supplementation. Generalized estimation equation, one way ANOVA were used to analyze continuous monitoring indexes and terminal indexes, respectively. Exercise capacity, skeletal muscle pathological features and relevant proteins were examined.

Results

The clinical results showed that VD3 could improve insulin secretion and decrease inflammation. Results of KKay mice exhibited that VD3 not only ameliorate glycolipid metabolism and inflammatory indicators, but also regulated pathological changes of skeletal muscle and exercise capacity. Mechanistically, our results demonstrated that VD3 could inhibit the TLR4/NFκB and activate PI3K/AKT signaling pathway.

Conclusion

Collectively, the study indicated that VD3 exerts its beneficial effects by inhibiting TLR4/NFκB to decrease inflammatory response, and activating PI3K/AKT signaling pathway to regulate glucose homeostasis.

Section snippetsINTRODUCTION

Prediabetes is a medical condition characterized by elevated blood glucose levels that exceed the normal range but fall below the diagnostic threshold for diabetes. This condition is associated with an increased risk of developing type 2 diabetes mellitus (T2DM) and complications related to diabetes [1,2]. As of 2021, it is estimated that there are 319 million adults (6.2%) with impaired fasting glucose (IFG) and 541 million adults (10.6%) with impaired glucose tolerance (IGT) [1]. The

Ethical approval

Our clinical data collection conducted according to the guidelines of the Declaration of Helsinki, all animal experimental protocol were performed sternly compliance with the National Research Council Guide for the Care and Use of Laboratory Animals, and approved by Medical Ethics Committee of Zhengzhou University (ZZUGZR2018-035, ZZUIRB2021-GZR0141). The trial was registered at www.chictr.org.cn as ChiCTR1900024872. Informed consent was obtained from all subjects involved in the study.

Clinical studies

We

Characteristics of participants

As shown in Fig. S1, we screened prediabetes and divided them into two groups: vitamin D group (n=60) and placebo group (n=62). Those who used gastrointestinal medication (n=11) or lacked complete biological samples (n=29) were excluded. Eventually, thirty age- and gender-matched participants for each group were included after pairing.

Table 1 displayed the baseline demographic, clinical and lifestyle characteristics for a total of 60 participants in vitamin D and placebo groups. The vitamin D

DISCUSSION

Since T2DM is a serious, chronic disease, patients will get appropriate medication therapy, nutritional advice, lifestyle modifications, and other interventions after receiving clinical diagnosis, which may become confounding variables when exploring the possible link between vitamin D and diabetes [25], [26], [27]. Thus, the investigation of vitamin D's impact on glucose and lipid metabolism in prediabetic participants is advantageous for ruling out the impact of confounding variables. KKay

CONCLUSIONS

Collectively, our study indicated that vitamin D3 exerts it beneficial effects by inhibiting TLR4/NFκB to decrease the inflammatory response, and activating the PI3K/AKT signaling pathway to regulate glucose homeostasis. Consequently, vitamin D3 may be utilized as a supplement to help prevent diabetes and effectively slow the development of prediabetes and diabetes.

Authors’ contribution

Yujing Zhang: Methodology, Data curation, Data analysis, Writing-original draft, Revision. Peng Ni: Data curation, Data analysis, Revision. Yufan Miao, Hao Chen, Lulu Tang, Hanlu Song: Data curation. Wenjie Li and Xing Li: Conceptualization, Methodology, Review & editing, Supervision, Project administration.

CRediT authorship contribution statement

Yujing Zhang: Writing – review & editing, Writing – original draft, Software, Methodology, Data curation. Peng Ni: Writing – review & editing, Software, Data curation. Yufan Miao: Data curation. Hao Chen: Data curation. Lulu Tang: Data curation. Hanlu Song: Data curation. Wenjie Li: Writing – review & editing, Supervision, Project administration, Methodology, Conceptualization. Xing Li: Writing – review & editing, Supervision, Project administration, Methodology, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by National Natural Science Foundation of China (grant numbers 82173515, 81872626, 82003454). We would like to acknowledge Sinopharm Xingsha Pharmaceuticals (Xiamen). Furthermore, we thank the participants for their willingness in this study.

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© 2024 Published by Elsevier Inc.