Liwan Fu, Hong Cheng, Jingfan Xiong, Pei Xiao, Xinying Shan, Yanyan Li, Yan Li, Xiaoyuan Zhao, Jie Mi
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引用次数: 0
Abstract
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.