Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Peking University Fifth School of Clinical Medicine, Beijing, China.
J Diabetes. 2023 Apr;15(4):349-361. doi: 10.1111/1753-0407.13378. Epub 2023 Mar 9.
To clarify the expression of N6-methyladenosine (m A) 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.
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 m A 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.
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]) m A-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.
Seven significantly altered m A 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 m A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.
阐明参与 2 型糖尿病（T2DM）发病机制的 N6-甲基腺苷（m A）调节剂的表达。我们进一步探讨了血清胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）水平与高危人群 T2DM 发病风险的关系。
从基因表达综合数据库中获取 GSE25724 基因表达数据集，并使用 R 包 ComplexHeatmap 生成聚类热图。使用配对 t 检验对非糖尿病对照和 T2DM 患者之间 13 个 m A RNA 甲基化调节剂的差异表达进行分析。采用横断面设计，纳入 393 例受试者（131 例新诊断的 T2DM 患者、131 例年龄和性别匹配的糖尿病前期患者和 131 例健康对照）。采用受限立方样条和逻辑回归模型对血清 IGF2BP3 浓度与 T2DM 的关系进行建模。
在 T2DM 患者胰岛样本中发现了 2 个上调（IGF2BP2 和 IGF2BP3）和 5 个下调（甲基转移酶样 3[METTL3]、烷基化修复同源蛋白 1[ALKBH1]、YTH 结构域家族 2[YTHDF2]、YTHDF3 和异质核核糖核蛋白[HNRNPC]）的 m A 相关基因。根据立方自然样条分析模型，经体重指数、腰围、舒张压、总胆固醇和甘油三酯校正后，血清 IGF2BP3 水平与 T2DM 发病风险之间存在 U 形关联。多变量逻辑回归显示，当血清 IGF2BP3 水平低于 0.62ng/mL 时，T2DM 的发病风险呈递增趋势（比值比 3.03[95%置信区间 1.23-7.47]）。
在 T2DM 中鉴定出 7 个明显改变的 m A RNA 甲基化基因。在中国普通成年人群中，血清 IGF2BP3 水平与 T2DM 发病风险之间存在 U 形关联。这项研究为进一步研究 m A RNA 甲基化，特别是血清 IGF2BP3 在 T2DM 风险评估中的作用提供了重要证据。
