Bahreiny Seyed Sobhan, Khaksar Mohammad Ali, Karamali Negin, Dabbagh Mohammad Reza, Hoseinnejad Akbar, Mohammadpour Fard Reza, Bahreiny Zahra Sadat, Aghaei Mojtaba, Sakhavarz Tannaz, Zahedian Mehdi
Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Poorsina Ave, Tehran, Iran.
Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Clin Exp Med. 2025 Jun 30;25(1):224. doi: 10.1007/s10238-025-01755-3.
Insulin sensitivity, resistance, and pancreatic beta-cell function play key roles in metabolic and reproductive health. Despite the known role of glucose-insulin homeostasis in female reproductive health, the association and regression modeling of estimated glucose disposal rate (eGDR), homeostatic model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-β), and insulin disposition index (Insulin-DI) with female infertility remain unclear. This cross-sectional study aimed to assess the associations between insulin-related indices and female infertility. This study examined data from 2832 women aged 18-45 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-2023 cycles. To evaluate the associations between four insulin-related indices and infertility, multivariable logistic regression, generalized additive models, and threshold effect analyses were applied, while controlling for relevant sociodemographic, lifestyle, and metabolic confounders. Furthermore, integrated meta-analysis across models, distributional analysis, subgroup and interaction analyses were conducted to explore potential effect modifications. eGDR showed a strong inverse association with infertility across all models (OR range: 0.636-0.85, p < 0.001), with a significant nonlinear pattern (p = 0.003) and a threshold at 4.59. HOMA-IR was positively associated in unadjusted models (OR = 1.147, p < 0.001) but lost significance after full adjustment. HOMA-β showed a weak positive association (OR = 1.003, p = 0.0227), while Insulin-DI was inversely related to infertility only in unadjusted models. Subgroup analyses revealed significant effect modifications by BMI and age, especially for eGDR and HOMA-IR. Reduced insulin sensitivity, as indicated by lower eGDR, is strongly linked to higher infertility risk. HOMA-IR and Insulin-DI also show threshold-based nonlinear associations.
胰岛素敏感性、抵抗性及胰岛β细胞功能在代谢和生殖健康中起关键作用。尽管已知葡萄糖-胰岛素稳态在女性生殖健康中的作用，但估计葡萄糖处置率（eGDR）、胰岛素抵抗稳态模型评估（HOMA-IR）、β细胞功能（HOMA-β）和胰岛素处置指数（胰岛素-DI）与女性不孕症之间的关联及回归模型仍不明确。这项横断面研究旨在评估胰岛素相关指标与女性不孕症之间的关联。本研究分析了2832名年龄在18至45岁之间、参与2017 - 2023年周期美国国家健康与营养检查调查（NHANES）的女性的数据。为评估四个胰岛素相关指标与不孕症之间的关联，应用了多变量逻辑回归、广义相加模型和阈值效应分析，同时控制了相关的社会人口统计学、生活方式和代谢混杂因素。此外，进行了跨模型的综合荟萃分析、分布分析、亚组分析和交互分析，以探索潜在的效应修饰。在所有模型中，eGDR与不孕症呈强烈负相关（OR范围：0.636 - 0.85，p < 0.001），具有显著的非线性模式（p = 0.003），阈值为4.59。HOMA-IR在未调整模型中呈正相关（OR = 1.147，p < 0.001），但在完全调整后失去显著性。HOMA-β呈弱正相关（OR = 1.003，p = 0.0227），而胰岛素-DI仅在未调整模型中与不孕症呈负相关。亚组分析显示，BMI和年龄存在显著的效应修饰，尤其是对于eGDR和HOMA-IR。较低的eGDR表明胰岛素敏感性降低，与较高的不孕症风险密切相关。HOMA-IR和胰岛素-DI也显示出基于阈值的非线性关联。
