Hippocampal integrity is highly susceptible to metabolic dysfunction, yet its mechanisms are not well defined. We studied 126 healthy individuals aged 23–61 years. Insulin resistance (IR) was quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Body mass index (BMI), adiposity, fasting insulin, glucose, leptin as well as structural neuroimaing with automatic hippocampal subfield segmentation were performed. Data analysis using unsupervised machine learning (k-means clustering) identified two subgroups reflecting a pattern of more pronounced hippocampal volume reduction being concurrently associated with greater adiposity and insulin resistance; the hippocampal volume reductions were uniform across subfields. Individuals in the most deviant subgroup were predominantly women (79 versus 42 %) with higher BMI [27.9 (2.5) versus 30.5 (4.6) kg/m²], IR (SSPG concentration, [156 (61) versus 123 (70) mg/dL] and leptinemia [21.7 (17.0) versus 44.5 (30.4) μg/L]. The use of person-based modeling in healthy individuals suggests that adiposity, insulin resistance and compromised structural hippocampal integrity behave as a composite phenotype; female sex emerged as risk factor for this phenotype.

海马完整性极易受到代谢功能障碍的影响，但其机制尚不明确。我们研究了 126 名年龄在 23-61 岁之间的健康人。通过在胰岛素抑制试验期间测量稳态血浆葡萄糖 (SSPG) 浓度来量化胰岛素抵抗 (IR)。进行了体重指数 (BMI)、肥胖、空腹胰岛素、葡萄糖、瘦素以及具有自动海马子区域分割的结构神经成像。使用无监督机器学习（k 均值聚类）进行的数据分析确定了两个亚组，反映了海马体积减少更明显的模式，同时与更大的肥胖和胰岛素抵抗相关；海马体积的减少在各个子区域是一致的。² ]、IR（SSPG 浓度 [156 (61) 对 123 (70) mg/dL] 和瘦素血症 [21.7 (17.0) 对 44.5 (30.4) μg/L]。在健康个体中使用基于人的模型表明肥胖、胰岛素抵抗和受损的海马结构完整性表现为复合表型；女性成为该表型的危险因素。