Groselj Urh, Kafol Jan, Sikonja Jaka, Mlinaric Matej, Sket Robert, Remec Ziga Iztok, Kovac Jernej, Drole Torkar Ana, Suput Omladic Jasna, Repic Lampret Barbka, Battelino Tadej, Kotnik Primoz
Department of Endocrinology, Diabetes, and Metabolic Diseases, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Am J Prev Cardiol. 2025 Jun 4;23:101016. doi: 10.1016/j.ajpc.2025.101016. eCollection 2025 Sep.
Early detection of insulin resistance (IR) and obesity-related complications is crucial for preventing type 2 diabetes. This study aimed to identify dynamic metabolic biomarkers for more precise early detection of IR and metabolic abnormalities.
This cross-sectional cohort study evaluated IR and metabolic biomarkers in 403 children with obesity (median age 13.18 years, 51.3 % female, 98.5 % with obesity) using an enhanced oral glucose tolerance test (eOGTT). IR was assessed via four indices, with the Matsuda Insulin Sensitivity Index (ISI-M) used as the primary measure. Participants were stratified into quartiles based on ISI-M.
Participants with the highest IR (Q1) were older ( = 0.002), had a higher body mass index, were in a more advanced pubertal stage ( < 0.001), and had significantly elevated glucose and insulin levels ( < 0.001 for both) compared to the most insulin sensitive (Q4), with significant differences observed across all quartiles ( < 0.050 for all). Insulin at 120 min demonstrated excellent diagnostic accuracy for IR (AUC=0.958). Triglyceride levels in Q1 showed minimal decline during the eOGTT, while greater declines were observed with increasing insulin sensitivity ( = 0.002 across quartiles), suggesting that a lack of decline in triglycerides may help identify IR. High-sensitivity C-reactive protein levels increased with IR ( = 0.024). Baseline beta-hydroxybutyrate levels were highest in the Q4 and showed the greatest absolute decrease during the eOGTT, compared to Q1 ( < 0.001 for both).
We validated established IR markers in children with obesity, while demonstrating that eOGTT may offer improved characterization and earlier identification of those at risk for metabolic complications.
早期发现胰岛素抵抗(IR)及肥胖相关并发症对于预防2型糖尿病至关重要。本研究旨在识别动态代谢生物标志物,以更精确地早期检测IR和代谢异常。
这项横断面队列研究采用强化口服葡萄糖耐量试验(eOGTT)评估了403名肥胖儿童(中位年龄13.18岁,51.3%为女性,98.5%患有肥胖症)的IR和代谢生物标志物。通过四个指标评估IR,以松田胰岛素敏感性指数(ISI-M)作为主要测量指标。参与者根据ISI-M分为四分位数。
与胰岛素敏感性最高的参与者(Q4)相比,IR最高的参与者(Q1)年龄更大(P = 0.002),体重指数更高,青春期阶段更 advanced(P < 0.001),血糖和胰岛素水平显著升高(两者均P < 0.001),所有四分位数之间均观察到显著差异(所有P < 0.050)。120分钟时的胰岛素对IR具有出色的诊断准确性(AUC = 0.958)。Q1中的甘油三酯水平在eOGTT期间下降最小,而随着胰岛素敏感性增加下降幅度更大(四分位数间P = 0.002),这表明甘油三酯缺乏下降可能有助于识别IR。高敏C反应蛋白水平随IR升高(P = 0.024)。与Q1相比,Q4中的基线β-羟基丁酸水平最高,且在eOGTT期间绝对下降幅度最大(两者均P < 0.001)。
我们验证了肥胖儿童中已有的IR标志物,同时表明eOGTT可能有助于更好地表征和更早地识别有代谢并发症风险的儿童。