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

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: Diabetes mellitus, Membrane micropolarity, Red blood cells, Fluorescence lifetime microscopy, Metabolic imaging, Personalized medicin

Clinical Study Magnetic Resonance Comparison of Left-Right Heart Volumetric and Functional Parameters in Thalassemia Major and Thalassemia Intermedia Patients

Objectives. To evaluate a population of asymptomatic thalassemia major (TM) and thalassemia intermedia (TI) patients using cardiovascular magnetic resonance (CMR). We supposed that TI group could be differentiated from the TM group based on 2 * and that the TI group could demonstrate higher cardiac output. Methods. A retrospective analysis of 242 patients with TM and TI was performed (132 males, 110 females; mean age 39.6 ± 8 years; 186 TM, 56 TI). Iron load was assessed by 2 * measurements; volumetric functions were analyzed using steady-state-free precession sequences. Results. Significant difference in left-right heart performance was observed between TM with iron overload and TI patients and between TM with iron overload and TM without iron overload ( &lt; 0.05); no significant differences were observed between TM without iron overload and TI patients. A significant correlation was observed between 2 * and ejection fraction of right ventricle-(RV-) ejection fraction of left ventricle (LV); an inverse correlation was present among 2 * values and end-diastolic volume of LV, end-systolic volume of LV, stroke volume of LV, end-diastolic volume of RV, end-systolic volume of RV, and stroke volume of RV. Conclusions. CMR is a leading approach for cardiac risk evaluation of TM and TI patients

Magnetic Resonance Comparison of Left-Right Heart Volumetric and Functional Parameters in Thalassemia Major and Thalassemia Intermedia Patients

Objectives. To evaluate a population of asymptomatic thalassemia major (TM) and thalassemia intermedia (TI) patients using cardiovascular magnetic resonance (CMR). We supposed that TI group could be differentiated from the TM group based on T2∗ and that the TI group could demonstrate higher cardiac output. Methods. A retrospective analysis of 242 patients with TM and TI was performed (132 males, 110 females; mean age 39.6±8 years; 186 TM, 56 TI). Iron load was assessed by T2∗ measurements; volumetric functions were analyzed using steady-state-free precession sequences. Results. Significant difference in left-right heart performance was observed between TM with iron overload and TI patients and between TM with iron overload and TM without iron overload (P<0.05); no significant differences were observed between TM without iron overload and TI patients. A significant correlation was observed between T2∗ and ejection fraction of right ventricle- (RV-) ejection fraction of left ventricle (LV); an inverse correlation was present among T2∗ values and end-diastolic volume of LV, end-systolic volume of LV, stroke volume of LV, end-diastolic volume of RV, end-systolic volume of RV, and stroke volume of RV. Conclusions. CMR is a leading approach for cardiac risk evaluation of TM and TI patients

Obesity is associated with in vivo platelet activation and impaired responsiveness to once-daily, low-dose aspirin

Obesity is raising worldwide, increases cardiovascular risk, modifies body composition and organ function, and potentially affects drug's pharmacokinetics and/or pharmacodynamics

Decline of the lung function and quality of glycemic control in type 2 diabetes mellitus

The aim of this study was to verify to which extent in type 2 diabetes mellitus respiratory function and respiratory muscle efficiency decline over time in relation to the quality of glycemic control (GC)

The oxidative modification of von Willebrand factor is associated with thrombotic angiopathies in diabetes mellitus.

The thrombogenic activity of Von Willebrand factor (VWF) is proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. Oxidation of VWF severely impairs its proteolysis by the metalloprotease. This study was aimed at assessing in patients with type 1 and type 2 diabetes whether protein carbonyls, marker of oxidative stress, are associated with both the level and oxidation status of VWF as well as with micro- and macroangiopathic complications. Eighty-three diabetic patients (41 type 1 and 42 type 2 diabetic subjects) and their respective eighty-three healthy controls were studied after verifying the availability, through institutional databases, of clinical biochemistry records spanning at least 3 years. VWF and protein carbonyls were measured by immunoassays, whereas VWF multimers were studied by SDS-agarose gel electrophoresis. Type 2 diabetic subjects had higher levels of VWF antigen (VWF:ag), VWF activity (VWF:act) and plasma proteins\u2019 carbonyls compared to both their controls and type 1 diabetic subjects. Moreover, high molecular weight VWF multimers and specific VWF-bound carbonyls were significantly increased in subjects with micro- and macro-angiopathic complications. In both type 1 and type 2 diabetic subjects, ADAMTS-13 activity was in the normal range. In a multivariable analysis, only VWF-bound carbonyls were significantly associated with any form of thrombotic angiopathy in the entire group of T1- and T2 diabetic patients. These data provide first evidence that not only high VWF levels but also its oxidation status and the presence of high molecular weight VWF multimers that are not observed in SDS-agarose gel electrophoresis of normal subjects are associated with thrombotic angiopathies in diabetes mellitus. These findings may help identify diabetic patients particularly at risk for these complications and elucidate a new pathophysiological mechanism of thrombotic angiopathies in this clinical settin

Multivariable-adjusted^* logistic regression for thrombotic angiopathies with haemostatic and oxidation variables in T1– and T2DM patients (n = 83).

*<p>Adjusted for age and sex.</p

Haemostatic and oxidative biomarker levels in T1- and T2-DM patients and respective controls.

*<p>Comparison with respective controls;</p>**<p>Comparison between type 1 and type 2 patients.</p>§<p>The values of mean±SD are listed in the table.</p

Correlation between total carbonyl content of plasma proteins and that of VWF purified from plasma samples of type 2 diabetes patients.

<p>The continuous line was drawn according to this phenomenological equation VWFcarb = (VWFcarb)max x (Pcarb)h/(P50h+Pcarbh), where (VWFcarb)max is the asymptotic value of VWF carbonyls (best fit value: 587±146 pmol/mg), Pcarb is the carbonyl content of plasma proteins, h is an exponential parameter (best fit = 3.6±0.6) and P50 is the concentration of plasma proteins carbonyls equal to (VWFcarb)max/2 (best fit: 706±107 pmol/mg). The vertical bars are the standard errors. In the inset, the SDS-PAGE gel (4–12%) of the purified and reduced VWF preparation is shown. On the left the molecular weight standards are also shown.</p