Liwan Fu, Hong Cheng, Jingfan Xiong, Pei Xiao, Xinying Shan, Yanyan Li, Yan Li, Xiaoyuan Zhao, Jie Mi
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Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).</p><p><strong>Results: </strong>In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.</p><p><strong>Conclusions: </strong>Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. 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引用次数: 0
摘要
目的目的是研究炎症生物标志物在身体成分对血糖特征和2型糖尿病的因果效应中的中介作用：方法：采用回顾性观察研究和孟德尔随机化（MR）研究。观察性分析使用了 4717 名 6-18 岁中国儿童和青少年的数据，这些儿童和青少年接受了双能 X 射线吸收测定法检测身体成分。MR分析基于英国生物库、deCODE2021、葡萄糖和胰岛素相关性状元分析联盟（MAGIC）和其他大型联盟的汇总统计数据。炎症生物标志物包括瘦素、脂肪连素、骨钙素、成纤维细胞生长因子23（FGF23）和甲状旁腺激素（PTH）：在一项回顾性观察研究中，脂肪量的增加通过FGF23对胰岛素抵抗稳态模型评估（HOMA-IR）和胰岛β细胞功能稳态模型评估（HOMA-β）产生了积极影响，而无脂肪量则产生了相反的影响。PTH和骨钙素在脂肪量和无脂肪量与空腹血糖、空腹胰岛素和HOMA-IR的关系中发挥了重要作用（均为p 结论：PTH和骨钙素在脂肪量和无脂肪量与空腹血糖、空腹胰岛素和HOMA-IR的关系中发挥了重要作用：我们的研究结果表明，不同的身体成分会通过不同的炎症生物标志物对血糖特征和 2 型糖尿病产生不同的影响。这些发现可能有助于根据不同血糖状态下的炎症生物标志物对身体成分进行有针对性的管理。
Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.
Objective: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.
Methods: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).
Results: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.
Conclusions: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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