Bianchetti Giada, Di Giacinto Flavio, Pitocco Dario, Rizzi Alessandro, Rizzo Gaetano Emanuele, De Leva Francesca, Flex Andrea, di Stasio Enrico, Ciasca Gabriele, De Spirito Marco, Maulucci Giuseppe
Fondazione Policlinico Universitario A, Gemelli IRCSS, Rome, Italy.
Istituto di Fisica, Università Cattolica Del Sacro Cuore, Rome, Italy.
Anal Chim Acta X. 2019 Oct 14;3:100030. doi: 10.1016/j.acax.2019.100030. eCollection 2019 Nov.
Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes.
糖尿病类型的分类对于临床医生诊断和选择正确的治疗方案极为重要。1型和2型糖尿病患者中,膜蛋白和跨膜蛋白的糖基化、氧化及其他翻译后修饰,以及胆固醇稳态受损,可改变红细胞(RBC)质膜的脂质密度、堆积和相互作用,进而改变其膜微极性。这可以通过测定膜相对介电常数在亚微米尺度上进行估算,膜相对介电常数是电荷间电场相对于真空减小的因子。在此,我们使用一种对膜微极性敏感的探针来监测健康受试者(n = 16)以及1型糖尿病(T1DM,n = 10)和2型糖尿病(T2DM,n = 24)患者红细胞的变化,以提供一种经济高效的糖尿病分类补充指标。我们发现,与健康对照患者相比,T2DM患者的膜微环境极性较小,而T1DM患者的膜微环境极性较大。三组之间的微极性差异具有统计学意义(p < 0.01)。研究了血清胆固醇池在决定这些差异中的作用,并考虑了其他可能改变探针反应的因素,以期开发一种基于RBC膜微极性的临床检测方法。这些初步数据为开发一种创新检测方法铺平了道路,该方法可能成为1型和2型糖尿病诊断及病情监测的工具。