Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de Cádiz, Cádiz, 11009, Spain.
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Cardiovasc Diabetol. 2024 Aug 27;23(1):315. doi: 10.1186/s12933-024-02412-x.
Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity.
The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis.
Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload.
Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.
胰岛素抵抗是典型肥胖症和代谢综合征并发症的常见前兆。然而，由于其病理生理学的复杂性和异质性，准确的诊断仍然难以实现。在此，我们探讨了口服葡萄糖耐量试验中胰岛素分泌动力学作为替代标志物来识别疾病严重程度不同代谢表型的效用。
研究人群由肥胖和胰岛素抵抗的儿童组成，根据餐后胰岛素峰值时间（即早期、中期和晚期峰值）进行分层，从这些儿童中采集空腹和餐后血浆和红细胞进行代谢组学分析。
胰岛素晚峰值的儿童比早期反应者表现出更差的心血管代谢健康（即更高的血压、血糖和 HOMA-IR 评分）。这些受试者的代谢物变化也更为明显，反映出能量平衡、氧化应激、胆固醇和磷脂代谢以及不健康饮食习惯的失败。此外，胰岛素晚峰值与代谢灵活性受损有关，这反映在葡萄糖过载时调节线粒体能量途径和抗氧化防御的能力受损。
综上所述，这些发现表明，胰岛素抵抗可能包含几种表型亚型，这些亚型以儿童肥胖中发生的不同代谢紊乱的逐渐加重为特征，可作为严重程度的预测标志物。
