Aim: This study investigates prothymosin-α (ProT-α), an immunomodulatory protein, as a potential biomarker for insulin resistance in gestational diabetes (GDM), and as a predictor of fetal growth by 20 weeks of gestation (wg). Methods: Forty-six women with singleton pregnancies were classified into GDM (n = 8) and normal glucose tolerance (NGT; n = 38) groups based on 75 g OGTT results. Maternal glucose, insulin, cytokines, and ProT-α levels were measured, and fetal growth was assessed by ultrasound at 20 wg, focusing on abdominal circumference (AC) and estimated fetal weight (EFW) percentiles. Results: Women with GDM were older, had a higher BMI, glucose, and insulin levels, with fetuses showing higher AC and EFW percentiles. IL-8, TNFα, and IL-1α were lower in the GDM group, while ProT-α was also lower but not significantly. ProT-α inversely correlated with EFW percentiles, independent of GDM. Regression analysis identified 2-hour post-load glucose, VEGF, and EGF as positive predictors of fetal growth acceleration, while IL-10 and ProT-α were negative predictors. Conclusions: Fetal growth is influenced by maternal glucose, inflammation, and angiogenesis. ProT-α may serve as an independent biomarker for predicting fetal growth in early pregnancy, suggesting further investigation into its role in GDM, obesity, and insulin resistance.

Chronic kidney disease (CKD) has now reached pandemic proportions but risk prediction towards end-stage kidney disease (ESKD) remains challenging. Kidney fibrosis is a key determinant in the transition from CKD to ESKD. In this prospective study, we investigated the prognostic significance of urinary Marinobufagenin (uMBG), a cardiotonic steroid with acknowledged pro-fibrotic activity, for stratifying the risk of CKD progression in individuals with non-advanced renal disease. After baseline uMBG measurements, 108 CKD patients (eGFR 40.54 ± 17 mL/min/1.73 m²) were prospectively followed up to 24 months. The study (renal) endpoint was a composite of serum creatinine doubling, eGFR decline >25% from baseline values, or ESKD requiring chronic renal replacement therapy. During follow-up (mean 21 months), 32.4% of patients had progressive CKD. These individuals displayed almost halved baseline uMBG excretion as compared to others (P < 0.0001). At ROC analysis uMBG showed a remarkable diagnostic capacity on CKD progression (AUC 0.898) and patients with uMBG ≤310 pmol/L (Best ROC-derived cut-off) had a significantly faster progression to the endpoint (Log-rank 57.9; P < 0.0001). Restricted cubic splines fitting Cox-regression analyses (Fig. 1) revealed that the risk association between uMBG and CKD progression was best described by a curvilinear, inverse J-shaped trend, the highest risk associated with very low uMBG levels. This trend remained unaffected by adjustment for age, baseline eGFR, and 24 h-proteinuria. Low urinary excretion of MBG is an independent prognostic factor for CKD progression in patients with non-advanced CKD. These findings suggest that uMBG may serve as a valuable biomarker for early risk stratification in CKD. Further validation in larger cohorts is needed to confirm its role in clinical practice.

Sarcopenia is a common and debilitating condition in patients with end-stage kidney disease (ESKD) undergoing peritoneal dialysis (PD). Its development is influenced by multiple factors, including mitochondrial dysfunction. The mitochondrial open reading frame of 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide promoting muscle growth which levels are imbalanced in ESKD. Yet, its role in sarcopenia risk in PD patients remains underexplored. This study aimed to assess the balance of MOTS-c in chronic PD patients and investigate its association with sarcopenia risk. In this observational study, 32 chronic PD patients were assessed for sarcopenia risk using the SARC-F questionnaire (a screening tool used to assess the risk of sarcopenia), physical performance tests such as the 30 seconds chair stand (30SCT) and handgrip tests, and anthropometric measures. Blood, urine and peritoneal fluid samples were collected, and MOTS-c was measured using an ELISA kit. The renal (u/sMOTS-c) and peritoneal (d/s MOTS-c) clearances of this substance were also computed. Correlations between MOTS-c levels and sarcopenia risk indicators were analyzed, and the diagnostic performance was evaluated using ROC analysis. PD patients at higher risk of sarcopenia (SARC-F≥ 2) exhibited significantly lower serum MOTS-c levels (p = 0.003) and higher dialysate MOTS-c levels (p = 0.04), suggesting increased peritoneal clearance (d/s MOTS-c; p = 0.003) (Fig. 1). sMOTS-c levels correlated directly with physical performance tests and negatively with the SARC-F score while dMOTS-c showed direct correlation with SARC-F score and waist-to-hip ratio and inverse correlation with the 30 SCT. The d/sMOTS-c clearance ratio correlated positively with the SARC-F score and waist-to-hip ratio, and negatively with the handgrip and 30 SCT tests. ROC analysis indicated that MOTS-c, particularly when combined with physical and anthropometric assessments, has potential to identify high sarcopenia risk in PD patients. Chronic PD may disrupt MOTS-c balance, potentially contributing to an increased risk of sarcopenia. Our findings suggest that MOTS-c could serve as a non-invasive biomarker for sarcopenia risk assessment in PD patients. Further studies are required to validate its utility in clinical practice and explore its potential therapeutic applications.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Keywords: glucose homeostasis, gene transcription, insulin resistance, insulin signaling, transcription factors

Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies.

The clinical use of anthracycline Doxorubicin as an antineoplastic drug in cancer therapy is limited by cardiotoxic effects that can lead to congestive heart failure. Recent studies have shown several promising activities of different species of the genus Ferula belonging to the Apiaceae Family. Ferula communis is the main source of Ferutinin-a bioactive compound isolated from many species of Ferula-studied both in vitro and in vivo because of their different effects, such as estrogenic, antioxidant, anti-inflammatory, and also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. However, the potential protective role of Ferutinin in myocardium impairment, caused by chemotherapeutic drugs, still represents an unexplored field. The aim of this study was to test the effects of Ferutinin rich-Ferula communis L. root extract (FcFE) at different concentrations on H9C2 cells. Moreover, we evaluated its antioxidant properties in cardiomyocytes in order to explore new potential therapeutic activities never examined before in other experimental works. FcFE, at a concentration of 0.25 µM, in the H9C2 line, significantly reduced the ROS production induced by H2O2 (50 µM and 250 µM) and traced the cell mortality of the H9C2 co-treated with Ferutinin 0.25 µM and Doxorubicin (0.5 µM and 1 µM) to control levels. These results showed that FcFE could protect against Doxorubicin-induced cardiotoxicity. Further molecular characterization of this natural compound may open the way for testing FcFE at low concentrations in vivo and in clinical studies as an adjuvant in cancer therapy in association with anthracyclines to prevent side effects on heart cells.

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit (“Mater-Domini”) of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals.

Background and Aims In end-stage kidney disease (ESKD) patients, atherosclerosis is a key-player for cardiovascular risk, being influenced by endothelial dysfunction, inflammation and mineral dysmetabolism. Omentin-1 is an adipokine involved in various pathological conditions (diabetes, metabolic syndrome, obesity), and has recently been studied as a prognostic factor for atherosclerosis progression and mortality in the general population. In this study, we evaluated the possible relationships between Omentin-1 and incipient carotid atherosclerosis in the clinical setting of ESKD. Method Circulating blood Omentin-1 levels were measured in a cohort of 77 asymptomatic ESKD patients (40 kidney transplant recipients, Ktx and 37 chronic hemodialysis patients, HD) and in 30 healthy controls. Carotid intima-media thickness (cIMT) was measured before a single HD session or before a Ktx outpatient visit. Pathological cIMT was defined for mean values > 0.9 mm and/or an unilateral cIMT above the 75th percentile. Results Omentin-1 levels were higher in the entire ESKD cohort than in healthy controls (324 [90.3-770] vs. 110 [35.4-240.9] pg/ml; p = 0.03). Ktx patients had lower levels than HD patients (p = 0.01) while higher Omentin-1 levels were found in HD patients (474.9 [197.2-1432.1] ng/ml) compared to both healthy subjects (p = 0.009) and Ktx (p = 0.01). Mean cIMT in all ESKD was 0.78 ± 0.32 mm. 36 patients (46.7%) with pathological cIMT values displayed lower Omentin-1 levels as compared with others (168.7 [51.1-457.8] vs 474.9 [197.2-1432.1] and p = 0.004). Multivariate correlations analyses indicated Omentin-1 as the stronger independent predictor of carotid atherosclerosis (β-0.687; p = 0.03) in the whole cohort, even more than age, total cholesterol and diastolic BP. Conclusion In ESKD patients, Omentin-1 reflects the severity of carotid atherosclerosis independently from traditional confounders and may serve as an additive biomarker for risk prediction and risk stratification. Future studies are awaited to confirm these preliminary findings in larger cohorts.

In recent years, there has been a dramatic increase in the number of pregnancies complicated by gestational diabetes mellitus (GDM). GDM occurs when maternal insulin resistance develops and/or progresses during gestation, and it is not compensated by a rise in maternal insulin secretion. If not properly managed, this condition can cause serious short-term and long-term problems for both mother and child. Lifestyle changes are the first line of treatment for GDM, but if ineffective, insulin injections are the recommended pharmacological treatment choice. Some guidance authorities and scientific societies have proposed the use of metformin as an alternative pharmacological option for treating GDM, but there is not yet a unanimous consensus on this. Although the use of metformin appears to be safe for the mother, concerns remain about its long-term metabolic effects on the child that is exposed in utero to the drug, given that metformin, contrary to insulin, crosses the placenta. This review article describes the existing lines of evidence about the use of metformin in pregnancies complicated by GDM, in order to clarify its potential benefits and limits, and to help clinicians make decisions about who could benefit most from this drug treatment.

Abstract Background and Aims Patients with end stage renal disease (ESKD) on hemodialysis (HD) have a high risk of cardiovascular (CV) events, this being mostly related to the presence of uraemic cardiomyopathy. A deregulation in the expression of various microRNAs (miRNAs: non-coding RNAs that regulate post-transcriptional gene expression) has previously been implied in pathological cardiac remodelling. Nevertheless, scarce evidence has accrued so far on a possible significance in CV morbidity and mortality in HD patients, in relationship with the presence of uremic cardiomyopathy. Method We run a pilot, prospective, multicentre cohort study involving 74 ESKD patients undergoing chronic HD from 3 different hospitals in Italy and Greece. HD patients underwent a thorough clinical, laboratory and echocardiography assessment and were then prospectively followed for 24 months or until the occurrence of a composite endpoint of (CV and all-cause) mortality or non-fatal CV events. Through a systematic review of the literature, we identified a small panel of miRNAs (30a-5p, 23a-3p,451a and let7d-5p), which levels are known to be altered in either major CV disorders and kidney failure. miRNAs were then measured in the blood of HD patients and in a small group of matched healthy controls. Results miRNAs 23a-3p (p<0.0001), 451a (p = 0.001), 30a-5p (p = 0.003) and let7d-5p (p <0.0001) were all reduced in HD patients as compared with controls. Significant correlations were found between miRNAs and indexes of cardiac dysfunction such as Vmax, TAPSE and E/E’, as well as with some other laboratory parameters such as uric acid, sodium, potassium, HDL and CRP. During follow-up, 30/74 patients (40.5%) reached the composite endpoint. In these individuals, all miRNAs but let7d-5p were significantly reduced at baseline (p<0.0001). As showed by multivariate Cox-regression analyses, miRNAs 23a-3p, 451a, 30a-5p were all predictors of the composite endpoint (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) and Kaplan-Meier analyses confirmed a faster progression to the endpoint in subjects with miRNAs levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to <0.0001; crude HRs 7.95 to 8.61; Figure 1). Conclusion Our study demonstrated that the evaluation of a very small panel of circulating miRNAs (30-5p, 23a–3p and 451a) may impart important prognostic information in chronic HD patients with respect to mortality and CV risk. Although the biological meaning of their deregulation remains unanswered, these preliminary findings may set the stage for larger investigation to generalize their usefulness as biomarkers, as well as possible therapeutic targets.

Sommario Il diabete mellito gestazionale (DMG), è il disordine endocrino-metabolico a maggiore prevalenza nelle donne in gravidanza e si associa a un alto rischio di complicanze materno-fetali. L’eziologia di tale condizione è complessa e multifattoriale, con fattori di rischio e meccanismi patogenetici in gran parte comuni a quelli del diabete mellito di tipo 2 (DMT2), il quale spesso compare nelle donne che hanno una storia di DMG anche a soli pochi anni di distanza dal parto. Tuttavia, mentre per la prevenzione del DMT2 gli interventi multimodali di modifica dello stile di vita, comprendenti programmi di attività fisica o esercizio fisico, uniti a cambiamenti nutrizionali e comportamentali, sono associati a benefici certi, lo stesso non vale per il DMG, per cui esistono evidenze scientifiche di natura osservazionale e sperimentale a volte contrastanti. Dall’analisi della letteratura più recente, riassunta in questa rassegna, emerge la necessità di spostare l’attenzione della ricerca sugli effetti di una prevenzione di precisione, che adatti il timing di inizio, la tipologia e l’intensità del programma di esercizio fisico per la prevenzione del DMG alle caratteristiche fisiologiche delle singole gestanti. Si ravvisa, inoltre, il bisogno di estendere la “finestra d’intervento” al periodo preconcezionale per massimizzare le possibilità di successo, soprattutto nelle donne ad alto rischio.

Background and aim—Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods—Thirty subjects, aged 45–65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results—Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions—The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.

Abstract Background and Aims In end-stage kidney disease (ESKD) patients, atherosclerosis is a key-player for cardiovascular risk, being influenced by endothelial dysfunction, inflammation and mineral dysmetabolism. Omentin-1 is an adipokine involved in various pathological conditions (diabetes, metabolic syndrome, obesity), and has recently been studied as a prognostic factor for atherosclerosis progression and mortality in the general population. In this study, we evaluated the possible relationships between Omentin-1 and incipient carotid atherosclerosis in the clinical setting of ESKD. Method Circulating blood Omentin-1 levels were measured in a cohort of 77 asymptomatic ESKD patients (40 kidney transplant recipients, Ktx and 37 chronic hemodialysis patients, HD) and in 30 healthy controls. Carotid intima-media thickness (cIMT) was measured before a single HD session or before a Ktx outpatient visit. Pathological cIMT was defined for mean values > 0.9 mm and/or an unilateral cIMT above the 75th percentile. Results Omentin-1 levels were higher in the entire ESKD cohort than in healthy controls (324 [90.3-770] vs. 110 [35.4-240.9] pg/ml; p = 0.03). Ktx patients had lower levels than HD patients (p = 0.01) while higher Omentin-1 levels were found in HD patients (474.9 [197.2-1432.1] ng/ml) compared to both healthy subjects (p = 0.009) and Ktx (p = 0.01). Mean cIMT in all ESKD was 0.78 ± 0.32 mm. 36 patients (46.7%) with pathological cIMT values displayed lower Omentin-1 levels as compared with others (168.7 [51.1-457.8] vs 474.9 [197.2-1432.1] and p = 0.004). Multivariate correlations analyses indicated Omentin-1 as the stronger independent predictor of carotid atherosclerosis (β-0.687; p = 0.03) in the whole cohort, even more than age, total cholesterol and diastolic BP. Conclusion In ESKD patients, Omentin-1 reflects the severity of carotid atherosclerosis independently from traditional confounders and may serve as an additive biomarker for risk prediction and risk stratification. Future studies are awaited to confirm these preliminary findings in larger cohorts.

BACKGROUND: Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin.METHODS: Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers.RESULTS: At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days.CONCLUSIONS: Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.

The demand of glucose monitoring devices and even of updated guidelines for the management of diabetic patients is dramatically increasing due to the progressive rise in the prevalence of diabetes mellitus and the need to prevent its complications. Even though the introduction of the first glucose sensor occurred decades ago, important advances both from the technological and clinical point of view have contributed to a substantial improvement in quality healthcare. This review aims to bring together purely technological and clinical aspects of interest in the field of glucose devices by proposing a roadmap in glucose monitoring and management of patients with diabetes. Also, it prospects other biological fluids to be examined as further options in diabetes care, and suggests, throughout the technology innovation process, future directions to improve the follow-up, treatment, and clinical outcomes of patients.

Already used for the treatment of some allergic and inflammatory diseases, such as asthma or atopic dermatitis, dupilumab has also been approved as add-on therapy for patients with CRSwNP, and it could represent the keystone to reducing the remission time as well as to improve healing and quality of life. On the other hand, the role of miRNAs as potential biomarkers of immune modulation is emerging. We analyzed the effects of a short-time treatment with dupilumab in patients with CRSwNP, analyzing the immune response modification as well as miRNAs modulations. First, in this early observation stage, all patients experienced remarkable improvement and were clinically stable. Indeed, we observed a significant decrease in CD4+ T cells and a significant reduction in total IgE (p < 0.05) and serum IL-8 levels (p < 0.01), indicating a reduction in the general inflammatory condition. In addition, we analyzed a panel of about 200 circulating miRNAs. After treatment, we noted a significant downregulation of hsa-mir-25-3p (p-value = 0.02415) and hsa-mir-185-5p (p-value = 0.04547), two miRNAs involved in the proliferation, inflammation, and dug-resistance, in accordance with the clinical status of patients. All these preliminary data aimed to identify new biomarkers of prognosis, identifiable with non-invasive procedures for patients. Further, these patients are still under observation, and others with different levels of responsiveness to treatment need to be enrolled to increase the statistical data.