Ramezani Tehrani Fahimeh, Fayaz Mohammad, Firouzi Faegheh, Azizi Fereidoun, Tohidi Maryam, Behboudi-Gandevani Samira
Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Foundation for Research & Education Excellence, Vestavia Hills, Alabama, USA.
Endocr Connect. 2025 Aug 29;14(8). doi: 10.1530/EC-25-0266. Print 2025 Aug 1.
Insulin resistance (IR) plays a central role in the pathophysiology of polycystic ovary syndrome (PCOS), yet its long-term trajectory across different phenotypes and obesity statuses remains unclear. This study aimed to model longitudinal IR patterns in women with PCOS, those meeting an isolated PCOS criterion, and healthy controls.
This population-based prospective study included 1,759 reproductive-aged women (18-49 years) from the Tehran Lipid and Glucose Study, categorized into PCOS (n = 287), isolated PCOS criterion (n = 536), and healthy control (n = 936) groups, stratified by BMI (<25 kg/m2, 25-29.99 kg/m2, and ≥30 kg/m2) and WC (<88 cm and ≥88 cm). Functional principal component analysis modeled HOMA-IR and fasting insulin level trajectories as sparse functional data.
Women with PCOS were younger (23.5 vs 25 and 28 years, P < 0.05) and had lower BMI than healthy controls (23.38 vs 24.46 kg/m2, P < 0.05), with no baseline differences in HOMA-IR. Both HOMA-IR and fasting insulin trajectories varied by obesity status. Women with PCOS and either obesity or central obesity showed a pronounced upward trend in IR over time, while those without general or central obesity exhibited more stable or improving patterns. In contrast, healthy and isolated criterion groups showed relatively stable or mildly increasing HOMA-IR and fasting insulin levels, with steeper increases in the presence of obesity.
This study provides new insights into the diverse trajectories of IR among women with PCOS, those with an isolated PCOS criterion, and healthy controls. Progressive worsening of IR was observed in women with PCOS and obesity, while those with PCOS without obesity showed improvement. Healthy and isolated criterion groups exhibited more stable patterns.
胰岛素抵抗（IR）在多囊卵巢综合征（PCOS）的病理生理过程中起核心作用，但其在不同表型和肥胖状态下的长期变化轨迹仍不清楚。本研究旨在对PCOS女性、符合孤立PCOS标准的女性以及健康对照者的纵向IR模式进行建模。
这项基于人群的前瞻性研究纳入了德黑兰脂质与葡萄糖研究中的1759名育龄女性（18 - 49岁），分为PCOS组（n = 287）、孤立PCOS标准组（n = 536）和健康对照组（n = 936），并按体重指数（BMI，<25 kg/m²、25 - 29.99 kg/m²和≥30 kg/m²）和腰围（WC，<88 cm和≥88 cm）进行分层。功能主成分分析将稳态模型评估的胰岛素抵抗（HOMA-IR）和空腹胰岛素水平轨迹建模为稀疏功能数据。
PCOS女性比健康对照者更年轻（23.5岁对25岁和28岁，P < 0.05），BMI更低（23.38 kg/m²对24.46 kg/m²，P < 0.05），HOMA-IR在基线时无差异。HOMA-IR和空腹胰岛素轨迹因肥胖状态而异。患有PCOS且伴有肥胖或中心性肥胖的女性，其IR随时间呈明显上升趋势，而无全身性或中心性肥胖的女性则表现出更稳定或改善的模式。相比之下，健康组和孤立标准组的HOMA-IR和空腹胰岛素水平相对稳定或轻度升高，在存在肥胖时升高更为明显。
本研究为PCOS女性、符合孤立PCOS标准的女性以及健康对照者中IR的不同变化轨迹提供了新见解。观察到患有PCOS且肥胖的女性IR逐渐恶化，而患有PCOS但无肥胖的女性则有所改善。健康组和孤立标准组表现出更稳定的模式。
