Martín-Saladich Queralt, Pareto Deborah, Simó Rafael, Ciudin Andreea, Aparicio Carolina, Hammawa Khadija, de la Calle Vargas Elena, Aguadé-Bruix Santiago, Giralt Marina, Ramirez-Serra Clara, González Ballester Miguel A, Herance José Raul
Medical Molecular Imaging Research Group, Vall Hebron Research Institute (VHIR), Nuclear Medicine and Radiology Departments, Vall d'Hebron University Hospital (VHUH), Autonomous University Barcelona (UAB), Barcelona 08035, Spain.
Department of Information and Communication Technologies, Pompeu Fabra University, 08018 Barcelona, Spain.
Brain Commun. 2025 Jun 12;7(3):fcaf213. doi: 10.1093/braincomms/fcaf213. eCollection 2025.
Previous studies in patients without Type 2 diabetes suggest that brain hypo- and hypermetabolic regions may indicate risk for cognitive disorders. We aimed to study these brain glucose uptake patterns in Type 2 diabetes to assess cognitive disorder risk and improve personalized management. Six hyper- and three hypometabolic regions were obtained through statistical parametric mapping, with cerebellar vermis and right superior temporal gyrus being the most relevant areas, respectively. Such allowed identification of two phenotypes via -means clustering: brain hypometabolic dominant (bU[-]) and hypermetabolic dominant (bU[+]). bU[-] displayed elevated markers of both Type 2 diabetes and cognitive disorders, specifically of secreted frizzled-related protein 1, a protein related to different neuronal pathologies. A classifier was developed (area under the curve = 0.84, true positive rate = 0.81 and true negative rate = 0.78) using a combination of biochemical features. Type 2 diabetes patients exhibit hypo- and hypermetabolic brain regions that phenotype into bU[-] and bU[+] by using the relationship between right superior temporal gyrus and cerebellar vermis, which defines the transition from one phenotype to the other. We suggest bU[-] patients are exposed to a higher risk of developing cognitive disorders based on the alteration of secreted frizzled-related protein 1 due to progressed type 2 diabetes, which can be identified using the proposed biomarker-based classification model.
先前针对非2型糖尿病患者的研究表明，大脑代谢减低和代谢增强区域可能提示认知障碍风险。我们旨在研究2型糖尿病患者的这些大脑葡萄糖摄取模式，以评估认知障碍风险并改善个性化管理。通过统计参数映射获得了六个代谢增强区域和三个代谢减低区域，其中小脑蚓部和右侧颞上回分别是最相关的区域。通过K均值聚类可识别出两种表型：大脑代谢减低主导型（bU[-]）和代谢增强主导型（bU[+]）。bU[-]表现出2型糖尿病和认知障碍的标志物升高，特别是分泌型卷曲相关蛋白1，这是一种与不同神经病理相关的蛋白质。利用生化特征组合开发了一种分类器（曲线下面积 = 0.84，真阳性率 = 0.81，真阴性率 = 0.78）。2型糖尿病患者表现出大脑代谢减低和代谢增强区域，通过利用右侧颞上回和小脑蚓部之间的关系将其表型化为bU[-]和bU[+]，这定义了从一种表型到另一种表型的转变。我们认为，基于2型糖尿病进展导致的分泌型卷曲相关蛋白1的改变，bU[-]患者发生认知障碍的风险更高，这可以使用所提出的基于生物标志物的分类模型来识别。
