Satheesh Gopika, Asokan Aneesh K, Vijayakumar Gadadharan, Chandran Mahesh, Surendran Arun, Simon Leena, Jaleel Abdul
Cardiovascular Diseases and Diabetes Biology, BRIC-Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thiruvananthapuram, Kerala, 695014, India.
Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Metabolomics. 2025 Aug 11;21(5):104. doi: 10.1007/s11306-025-02295-3.
Type 2 Diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycemia, often preceded by latent metabolic disruptions. Early detection of metabolic alterations can facilitate timely intervention to delay or prevent T2DM onset. Metabolic profiling offers a useful tool to identify novel biomarkers and early metabolic alterations before clinical manifestations.
This study aimed to identify early metabolic alterations and potential biomarkers predictive of T2DM in a cohort of healthy normoglycemic participants over a six-year follow-up.
A cohort of 94 healthy participants, both men and women aged 18-40, was studied at six-year intervals. Clinical and biochemical parameters were measured, and LC/MS/MS-based untargeted metabolomics analysis of plasma was performed at both baseline and follow-up.
At follow-up, 9 participants developed T2DM, 51 had prediabetes, and 34 remained normoglycemic. Increasing insulin resistance and elevated future T2DM risk were observed in both the prediabetes and normoglycemia groups. Metabolomics analysis identified phosphatidylethanolamine (PE) (20:3_18:0), 3beta,7alpha-dihydroxy-5-cholestenoate, and tridecanoic acid-as having good predictive capacity for future T2DM risk at baseline with alterations in PE (20:3_18:0), and tridecanoic acid persisting at follow-up.
The study highlights the potential of metabolomics in identifying early metabolic predictors of T2DM, emphasizing the need for early interventions in healthy normoglycemic young adults.
2型糖尿病（T2DM）是一种慢性代谢紊乱疾病，其特征为胰岛素抵抗和高血糖，通常在出现潜在代谢紊乱之后发生。早期发现代谢改变有助于及时进行干预，以延缓或预防T2DM的发病。代谢谱分析提供了一种有用的工具，可在临床表现出现之前识别新的生物标志物和早期代谢改变。
本研究旨在识别一组健康血糖正常参与者在六年随访期间T2DM的早期代谢改变和潜在预测生物标志物。
对94名年龄在18 - 40岁之间的健康参与者（男女均有）进行为期六年的队列研究。测量临床和生化参数，并在基线和随访时对血浆进行基于液相色谱/串联质谱的非靶向代谢组学分析。
随访时，9名参与者患T2DM，51名处于糖尿病前期，34名仍保持血糖正常。在糖尿病前期和血糖正常组中均观察到胰岛素抵抗增加和未来患T2DM风险升高。代谢组学分析确定磷脂酰乙醇胺（PE）（20:3_18:0）、3β,7α - 二羟基 - 5 - 胆甾烯酸和十三烷酸在基线时对未来T2DM风险具有良好的预测能力，其中PE（20:3_18:0）和十三烷酸的改变在随访时持续存在。
该研究突出了代谢组学在识别T2DM早期代谢预测指标方面的潜力，强调了对健康血糖正常的年轻成年人进行早期干预的必要性。
