Journal of Diabetes (Apr 2023)

血清IGF2BP3与2型糖尿病的U型关联:一项中国人群横断面研究

  • Xiaoying Wu,
  • Wei Wang,
  • Shujin Fan,
  • Lili You,
  • Feng Li,
  • Xiaoyun Zhang,
  • Hongshi Wu,
  • Juying Tang,
  • Yiqin Qi,
  • Wanting Feng,
  • Li Yan,
  • Meng Ren

DOI
https://doi.org/10.1111/1753-0407.13378
Journal volume & issue
Vol. 15, no. 4
pp. 349 – 361

Abstract

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Abstract Objective To clarify the expression of N6‐methyladenosine (m6A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin‐like growth factor 2 mRNA‐binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high‐risk population. Methods The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross‐sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age‐ and sex‐matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Results Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase‐like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6A‐related genes were found in islet samples of T2DM patients. A U‐shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23–7.47]) in model 4. Conclusion Seven significantly altered m6A RNA methylation genes were identified in T2DM. There was a U‐shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

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