Evaluating Red Blood Cells' Membrane Fluidity in Diabetes: Insights, Mechanisms, and Future Aspects

Aims: This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients. Materials and Methods: We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi-scale probe assessment, and machine learning integration for standardized fluidity measurement. Results: Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management. Conclusions: There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients

Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens

Sensing Biomechanical Alterations in Red Blood Cells of Type 1 Diabetes Patients: Potential Markers for Microvascular Complications

In physiological conditions, red blood cells (RBCs) demonstrate remarkable deformability, allowing them to undergo considerable deformation when passing through the microcirculation. However, this deformability is compromised in Type 1 diabetes mellitus (T1DM) and related pathological conditions. This study aims to investigate the biomechanical properties of RBCs in T1DM patients, focusing on identifying significant mechanical alterations associated with microvascular complications (MCs). We conducted a case-control study involving 38 T1DM subjects recruited from the Diabetes Care Unit at Fondazione Policlinico Gemelli Hospital, comprising 22 without MCs (control group) and 16 with MCs (pathological group). Atomic Force Microscopy was employed to assess RBC biomechanical properties in a liquid environment. We observed significant RBC stiffening in individuals with MCs, particularly during large indentations that mimic microcirculatory deformations. Univariate analysis unveiled significant differences in RBC stiffness (median difference 0.0006 N/m, p = 0.012) and RBC counts (median difference -0.39 x 1012/L, p = 0.009) between the MC and control groups. Bivariate logistic regression further demonstrated that combining these parameters could effectively discriminate between MC and non-MC conditions, achieving an AUC of 0.82 (95% CI: 0.67-0.97). These findings reveal the potential of RBC biomechanical properties as diagnostic and monitoring tools in diabetes research. Exploring RBC mechanical alterations may lead to the development of novel biomarkers, which, in combination with clinical markers, could facilitate the early diagnosis of diabetes-related complications

The pathogenesis of Charcot neuroarthropathy: current concepts

The pathogenesis of Charcot neuroarthropathy (CN) has been poorly understood by clinicians and scientists alike. Current researchers have made progress toward understanding the cause of CN and possible treatment options. The authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation, bone metabolism, and advanced glycation end products

Assessment of the influence of chewing pattern on glucose homeostasis through linear regression model

Objective: Maintaining plasma glucose homeostasis is vital for mammalian survival, but the masticatory function, which influences glucose regulation, has, to our knowledge, been overlooked. Research methods and procedures: In this study, we investigated the relationship between the glycemic response curve and chewing performance in a group of 8 individuals who consumed 80 g of apple. A device called "Chewing" utilizing electromyographic (EMG) technology quantitatively assesses chewing pattern, while glycemic response is analyzed using continuous glucose monitoring. We assessed chewing pattern characterizing chewing time (tchew), number of bites (nchew), work (w), power (wr), and chewing cycles (tcyc). Moreover, we measured the principal features of the glycemic response curve, including the area under the curve (a) and the mean time to reach the glycemic peak (tmean). We used linear regression models to examine the correlations between these variables. Results: t(chew), n(chew), and wr were correlated with a (R-2 = 0.44, P < 0.05 for t(chew) and n(chew), P < 0.001 for wr), and tmean was correlated with tchew (R-2 = 0.25, P < 0.05). These findings suggest that increasing chewing time and power, while reducing the number of chews, resulted in a wider glycemic curve and an earlier attainment of the glycemic peak. Conclusions: These results emphasize the influence of proper chewing techniques on blood sugar levels. Implementing correct chewing habits could serve as an additional approach to managing the glycemic curve, particularly for individuals with diabetes. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/

Advanced hybrid closed-loop system: first successful clinical case after total pancreatectomy

A 64-year-old woman has undergone in February 2019 total spleen-preserving pancreatectomy for cystic pancreatic neoplasia. In her medical history, in 2010 she also underwent total thyroidectomy because of thyroid cancer. She is a former smoker who quitted smoking in 2014. From February 2019, she assumes pancrelipase 10.000 UI daily as pancreatic replacement therapy and from 2010 levotiroxine for thyroid replacement. At the discharge, insulin therapy with multiple daily injections, supported by advanced educational therapeutic plan about carbohydrates counting, was started, but, after a severe hypoglycemic event, she developed an important fear of hypoglycemia with a consequent wrong approach to the insulin therapy, preferring to maintain glycemic values higher than 200 mg/dL in order to avoid hypoglycemia. Insulin therapy with continuous subcutaneous insulin infusion (CSII) was suggested, but she refused mainly because of discomfort. Yearly mean glycated hemoglobin (HbA1c) was 74 mmol/mol (8.9%). In December 2019, she was admitted to emergency room because of another severe hypoglycemia with loss of consciousness due to inappropriate insulin administration. After this event, patient started real-time continuous glucose monitoring (CGM—Medtronic Guardian Connect, Northridge California)

The "Adipo-Cerebral" Dialogue in Childhood Obesity: Focus on Growth and Puberty. Physiopathological and Nutritional Aspects

Overweight and obesity in children and adolescents are overwhelming problems in western countries. Adipocytes, far from being only fat deposits, are capable of endocrine functions, and the endocrine activity of adipose tissue, resumable in adipokines production, seems to be a key modulator of central nervous system function, suggesting the existence of an “adipo-cerebral axis.” This connection exerts a key role in children growth and puberty development, and it is exemplified by the leptin–kisspeptin interaction. The aim of this review was to describe recent advances in the knowledge of adipose tissue endocrine functions and their relations with nutrition and growth. The peculiarities of major adipokines are briefly summarized in the first paragraph; leptin and its interaction with kisspeptin are focused on in the second paragraph; the third paragraph deals with the regulation of the GH-IGF axis, with a special focus on the model represented by growth hormone deficiency (GHD); finally, old and new nutritional aspects are described in the last paragraph

Diabetes-Related Autoantibodies in Children With Acute Lymphoblastic Leukemia

[No abstract available

Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New KCNJ6 and DSCR4 Transcript Isoforms

Down syndrome (DS) is caused by trisomy of chromosome 21 and it is the most common genetic cause of intellectual disability (ID) in humans. Subjects with DS show a typical phenotype marked by facial dysmorphisms and ID. Partial trisomy 21 (PT21) is a rare genotype characterized by the duplication of a delimited chromosome 21 (Hsa21) portion and it may or may not be associated with DS diagnosis. The highly restricted Down syndrome critical region (HR-DSCR) is a region of Hsa21 present in three copies in all individuals with PT21 and a diagnosis of DS. This region, located on distal 21q22.13, is 34 kbp long and does not include characterized genes. The HR-DSCR is annotated as an intergenic region between KCNJ6-201 transcript encoding for potassium inwardly rectifying channel subfamily J member 6 and DSCR4-201 transcript encoding Down syndrome critical region 4. Two transcripts recently identified by massive RNA-sequencing (RNA-Seq) and automatically annotated on Ensembl database reveal that the HR-DSCR seems to be partially crossed by KCNJ6-202 and DSCR4-202 isoforms. KCNJ6-202 shares the coding sequence with KCNJ6-201 which is involved in many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells. DSCR4-202 transcript has the first two exons in common with DSCR4-201, the only experimentally verified gene uniquely present in Hominidae. In this study, we performed in silico and in vitro analyses of the HR-DSCR. Bioinformatic data, obtained using Sequence Read Archive (SRA) and SRA-BLAST software, were confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing on a panel of human tissues. Our data demonstrate that the HR-DSCR cannot be defined as an intergenic region. Further studies are needed to investigate the functional role of the new transcripts, likely involved in DS phenotypes

Arthrodesis in the Charcot foot: a systematic review

The Charcot foot is a condition characterized by a progressive derangement of the foot. The type of deformity and patient clinical conditions will lead to the proper surgical approach among exostectomy, arthrodesis (through external and/or internal fixation) and amputation. Many authors report good clinical outcomes performing the arthrodesis in Charcot foot; however, the choice of the most appropriate hardware is still an issue. The aim of this study is to analyze the outcomes of different hardware in midfoot and hindfoot Charcot arthrodesis