Wang Kai, Yu Guoyan, Yan Long, Lai Yi, Zhang Lingling
Department of Emergency, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, 311200, Zhejiang, China.
Department of Clinical Laboratory, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, 311200, Zhejiang, China.
Clin Exp Med. 2025 Aug 7;25(1):281. doi: 10.1007/s10238-025-01819-4.
Dyslipidemia, diabetes mellitus, and insulin resistance (IR) are intricately linked. In recent years, a series of novel lipid indices have emerged. Investigating their correlation with diabetes and IR is critical for early intervention. This study analyzed 19,780 National Health and Nutrition Examination Survey (NHANES) participants (1999-2020), examining the atherogenic index of plasma (AIP), Castelli risk index I (CRI-I) and II (CRI-II), estimated small dense LDL cholesterol (EsdLDL-C), non-HDL cholesterol-to-HDL cholesterol ratio (NHHR), and remnant cholesterol (RC). Covariates were selected via Boruta and LASSO regression. Multivariate logistic regression, restricted cubic splines, ROC, subgroup, and mediation analyses were employed, validated by sensitivity analyses. The prevalence of diabetes was 15.0%. After adjustment, four indices (excluding CRI-II and EsdLDL-C) were associated with diabetes. For Q4 vs Q1, AIP and RC showed significantly elevated risk (OR: 2.52 [2.07-3.07] and 2.13 [1.75-2.58], respectively). Regarding IR, all indices exhibited dose-dependent associations, with AIP (OR: 5.74 [5.00-6.59]) and RC (4.09 [3.58-4.67]) showing the strongest links. For diabetes diagnosis, AIP (AUC: 0.824) and RC (0.822) outperformed other lipid indices (cutoffs: 0.31, 31.0) but were less effective than fasting glucose and HbA1c. For IR, AIP (AUC: 0.837) and RC (0.830) remained superior among lipid indices and showed no significant diagnostic disadvantage vs IR-related indicators. Subgroup analyses indicated stronger AIP/RC-diabetes/IR associations in females. Mediation analyses showed HOMA-IR mediated 43.1% and 50.3% of AIP/RC-diabetes associations, more pronounced in older adults (> 65 years), males and those with BMI ≥ 25 kg/m, while fatty acid intake did not affect these mediators. All six indices correlate with IR, but only AIP and RC strongly associate with diabetes, mediated by HOMA-IR. Females show enhanced AIP/RC-diabetes links, while older, male, and overweight groups exhibit greater HOMA-IR mediation. And AIP or RC's diagnostic performance for IR is not inferior to other IR assessment indices. Thus, AIP and RC are prioritized biomarkers for diabetes and IR monitoring.
血脂异常、糖尿病和胰岛素抵抗（IR）之间存在着复杂的联系。近年来，一系列新的血脂指标不断涌现。研究它们与糖尿病和IR的相关性对于早期干预至关重要。本研究分析了19780名美国国家健康与营养检查调查（NHANES，1999 - 2020年）参与者，检测了血浆致动脉粥样硬化指数（AIP）、卡斯泰利风险指数I（CRI - I）和II（CRI - II）、估算的小而密低密度脂蛋白胆固醇（EsdLDL - C）、非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值（NHHR）以及残余胆固醇（RC）。通过Boruta和LASSO回归选择协变量。采用多变量逻辑回归、受限立方样条、ROC、亚组和中介分析，并通过敏感性分析进行验证。糖尿病患病率为15.0%。调整后，四个指标（不包括CRI - II和EsdLDL - C）与糖尿病相关。对于Q4与Q1，AIP和RC的风险显著升高（OR分别为：2.52 [2.07 - 3.07]和2.13 [1.75 - 2.58]）。关于IR，所有指标均呈现剂量依赖性关联，其中AIP（OR：5.74 [5.00 - 6.59]）和RC（4.09 [3.58 - 4.67]）的关联最强。对于糖尿病诊断，AIP（AUC：0.824）和RC（0.822）优于其他血脂指标（临界值：0.31，31.0），但不如空腹血糖和糖化血红蛋白有效。对于IR，AIP（AUC：0.837）和RC（0.830）在血脂指标中仍表现出色，与IR相关指标相比无明显诊断劣势。亚组分析表明，女性中AIP/RC与糖尿病/IR的关联更强。中介分析显示，HOMA - IR介导了AIP/RC与糖尿病关联的43.1%和50.3%，在老年人（>65岁）、男性和BMI≥25 kg/m²的人群中更为明显，而脂肪酸摄入并未影响这些中介作用。所有六个指标均与IR相关，但只有AIP和RC与糖尿病密切相关，且由HOMA - IR介导。女性中AIP/RC与糖尿病的联系增强，而老年、男性和超重人群中HOMA - IR的中介作用更大。并且AIP或RC对IR的诊断性能不低于其他IR评估指标。因此，AIP和RC是糖尿病和IR监测的优先生物标志物。
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