Wang Sujing, Shi Shuxiao, Jiang Xuanwei, Yang Guangrui, Wu Deshan, Li Kexin, Zhong Victor W, Du Xihao
Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Nutrients. 2025 Jul 27;17(15):2450. doi: 10.3390/nu17152450.
This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815-835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02-0.08 at 3 months and by 0.02-0.06 at 6 months for T2D remission. This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention.
本研究旨在确定与低热量饮食（LCD）干预后体重减轻和2型糖尿病（T2D）缓解相关的血浆外泌体微小RNA（miRNA）。对患有T2D的个体进行了为期6个月的旨在实现T2D缓解的饮食干预。参与者经历了一个为期3个月的强化体重减轻阶段，期间食用LCD（815 - 835千卡/天），以及一个为期3个月的体重维持阶段（N = 32）。随机选择16名参与者，在基线、3个月和6个月时使用小RNA测序对血浆来源的外泌体miRNA谱进行表征。使用线性混合效应模型来识别应答者和非应答者之间差异表达的外泌体miRNA。使用差异表达miRNA的靶mRNA进行通路富集分析。逻辑回归模型评估差异表达miRNA对T2D缓解的预测价值。在这16名参与者中，6人体重减轻≥10%，12人实现了T2D缓解。18种外泌体miRNA，包括miR-92b-3p、miR-495-3p和miR-452b-5p，与T2D缓解和体重减轻显著相关。通路分析显示PI3K-Akt通路、FoxO信号通路和胰岛素受体结合方面存在富集。将包括miR-15b-3p、miR-26a-5p和miR-3913-5p在内的单个miRNA添加到基础模型中，在3个月时使T2D缓解的曲线下面积值提高了0.02 - 0.08，在6个月时提高了0.02 - 0.06。本研究确定了与LCD干预后T2D缓解和体重减轻相关的外泌体miRNA。几种外泌体miRNA可能作为LCD干预后T2D缓解的有价值预测指标。
