PMID- 36891946 OWN - NLM STAT- MEDLINE DCOM- 20230417 LR - 20230417 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 15 IP - 4 DP - 2023 Apr TI - U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population. PG - 349-361 LID - 10.1111/1753-0407.13378 [doi] AB - OBJECTIVE: To clarify the expression of N6-methyladenosine (m(6) 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. 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 m(6) 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. 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]) m(6) 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. CONCLUSION: Seven significantly altered m(6) 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(6) A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment. CI - (c) 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Wu, Xiaoying AU - Wu X AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. AD - Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Peking University Fifth School of Clinical Medicine, Beijing, China. FAU - Wang, Wei AU - Wang W AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Fan, Shujin AU - Fan S AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - You, Lili AU - You L AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Li, Feng AU - Li F AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Zhang, Xiaoyun AU - Zhang X AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Wu, Hongshi AU - Wu H AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Tang, Juying AU - Tang J AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Qi, Yiqin AU - Qi Y AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Feng, Wanting AU - Feng W AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Yan, Li AU - Yan L AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Ren, Meng AU - Ren M AUID- ORCID: 0000-0001-9935-1449 AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. LA - eng GR - 81900752/National Natural Science Foundation of China/ GR - U20A20352/National Natural Science Foundation of China/ GR - 2020B1111170009/Guangdong Clinical Research Center for Metabolic Diseases/ GR - 2019A1515011199/Natural Science Foundation of Guangdong Province/ PT - Journal Article DEP - 20230309 PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - EC 1.14.11.33 (AlkB Homolog 1, Histone H2a Dioxygenase) RN - EC 1.14.11.33 (ALKBH1 protein, human) RN - 0 (IGF2BP2 protein, human) RN - EC 2.1.1.- (Methyltransferases) RN - EC 2.1.1.62 (METTL3 protein, human) RN - 0 (RNA-Binding Proteins) RN - 0 (IGF2BP3 protein, human) SB - IM MH - Adult MH - Humans MH - AlkB Homolog 1, Histone H2a Dioxygenase/metabolism MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2 MH - East Asian People MH - Methyltransferases/genetics/metabolism MH - Risk Factors MH - *RNA-Binding Proteins/blood PMC - PMC10101838 OTO - NOTNLM OT - 2型糖尿病 OT - N6 -甲基腺苷(m6A) OT - N6-methyladenosine (m6A) RNA methylation OT - RNA甲基化 OT - gene expression omnibus OT - insulin-like growth factor 2 mRNA-binding protein (IGF2BP)3 OT - type 2 diabetes mellitus OT - 基因表达数据库 OT - 胰岛素样生长因子2 mRNA结合蛋白3 (IGF2BP3) COIS- The authors have nothing to disclose. EDAT- 2023/03/10 06:00 MHDA- 2023/04/17 06:41 PMCR- 2023/03/09 CRDT- 2023/03/09 05:32 PHST- 2023/02/03 00:00 [revised] PHST- 2022/09/12 00:00 [received] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/04/17 06:41 [medline] PHST- 2023/03/10 06:00 [pubmed] PHST- 2023/03/09 05:32 [entrez] PHST- 2023/03/09 00:00 [pmc-release] AID - JDB13378 [pii] AID - 10.1111/1753-0407.13378 [doi] PST - ppublish SO - J Diabetes. 2023 Apr;15(4):349-361. doi: 10.1111/1753-0407.13378. Epub 2023 Mar 9.