In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 μm in DM to 0.183 ± 0.124 μm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.

In this report we describe the identification of a novel DPB1 allele, DPB1*02014, found in an Italian Caucasian individual.The new allele was detected during routine HLA sequence‐based typing (SBT) for an individual undergoing bone marrow transplantation. DPB1*02014 was identical to DPB1*02012 except for a single nucleotide substitution in codon 72 (GTG→GTT). This nucleotide change represents a synonimous mutation, as both triplets code for a valine.This new allele has been submitted to GenBank and assigned the accession number AF326565. The WHO Nomenclature Committee has officially assigned the name DPB1*02014.

Background: Cell membrane fluidity of erythrocytes in patients with type 2 diabetes can be influenced by glycosylation processes, changes in lipid homeostasis and oxidative stress. Objectives: We have measured red blood cell membrane fluidity looking for differences between healthy people and diabetic subjects and also between diabetic patients affected by macroangiopathy (vascular diabetic foot) and not. Methods: We have enrolled 32 subjects: 8 healthy controls (group G0), 9 diabetic patients without macroangiopathy (G1) and 15 with macroangiopathy (G2). We have used an inverted confocal microscope to analyze images of erythrocytes labeled by the Laurdan probe, that varies its fluorescence emission based on the polarity of the membrane, discriminating between fluid-crystalline state (emission spectrum at 490 nm) and state gel-like (less fluid, emission spectrum at 440 nm). Results of fluidity analysis have been calculated as GP index, “generalized polarization” (G P=(I440 nm - I490 nm) / (I440 nm + I490 nm)), that assumes values between -1 and +1, where lower values tending to -1 indicate higher fluidity. Results: diabetic patients have an higher GP index compared to healthy subjects (p<0.01). GP mean value grows among the three groups: in G0 is 0.600956 (±0.005161), in G1 0.626324 (±0.015676) and in G2 0.641015 (±0.008644), with a GP index significantly higher in G2 than in G0 (p<0.01). We have found a direct correlation between GP and triglyceridemia mean value and an inverse correlation between GP mean value and HDL cholesterol mean value. Conclusions: Diabetic patients, compared to healthy subjects, have a less fluid cell membrane fluidity with a further reduction in patients affected by macroangiopathy. These results suggest the utility to integrate analysis of membrane fluidity with laboratory exams (like HbA1c) for an early identification of macroangiopathic complications.