Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes

Giada Bianchetti; Flavio Di Giacinto; Dario Pitocco; Alessandro Rizzi; Gaetano Emanuele Rizzo; Francesca De Leva; Andrea Flex; Enrico di Stasio; Gabriele Ciasca; Marco De Spirito; Giuseppe Maulucci

doi:10.1016/j.acax.2019.100030

Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes

Anal Chim Acta X. 2019 Oct 14:3:100030. doi: 10.1016/j.acax.2019.100030. eCollection 2019 Nov.

Authors

Giada Bianchetti^{1

2}, Flavio Di Giacinto^{1

2}, Dario Pitocco^{1

3}, Alessandro Rizzi^{1

3}, Gaetano Emanuele Rizzo^{1

3}, Francesca De Leva^{1

3}, Andrea Flex^{1

4}, Enrico di Stasio^{1

5}, Gabriele Ciasca^{1

2}, Marco De Spirito^{1

2}, Giuseppe Maulucci^{1

2}

Affiliations

¹ Fondazione Policlinico Universitario A, Gemelli IRCSS, Rome, Italy.
² Istituto di Fisica, Università Cattolica Del Sacro Cuore, Rome, Italy.
³ Diabetes Care Unit, Università Cattolica Del Sacro Cuore, Rome, Italy.
⁴ Cardiovascular Disease Division, Università Cattolica Del Sacro Cuore, Rome, Italy.
⁵ Istituto di Biochimica Clinica, Università Cattolica Del Sacro Cuore, Rome, Italy.

Abstract

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.

Keywords: DMPC, dimyristoylphosphatidylcholine; DPPC, dipalmitoilphosphatidylcholine; Diabetes mellitus; Fluorescence lifetime microscopy; HDL, high-density lipoproteins; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated Haemoglobin; LDL, low-density lipoproteins; LDL-C, low-density lipoprotein cholesterol; Membrane micropolarity; Metabolic imaging; PC, phosphatydilcholine; Personalized medicine; RBC, red blood cells; Red blood cells; T1DM, Type 1 Diabetes Mellitus; T2DM, Type 2 diabetes Mellitus.