Context:
Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus ...(T2DM).
Objectives:
The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism.
Design, Setting, and Patients:
This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures.
Results:
Sclerostin levels were significantly higher in T2DM patients than control subjects (P < 0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively associated with duration of T2DM (P = 0.064) and glycated hemoglobin (P = 0.074) independently of age in T2DM patients. Sclerostin was inversely related to bone turnover markers (P < 0.05) and positively related to lumbar spine, femoral neck, and total hip BMD (P < 0.05) in the T2DM group. Sclerostin was significantly lower in osteoporotic than nonosteoporotic patients with T2DM (P = 0.048).
Conclusions:
Circulating sclerostin is increased in T2DM independently of gender and age. Serum sclerostin is also correlated with duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients. Additional studies are needed to evaluate the role of sclerostin on bone metabolism in this population.
•The COVID-19 pandemic has impacted healthcare worldwide.•The consequences of the lockdowns in people with diabetes have not been sufficiently explored.•Almost all respondents agreed with the concept ...of telemedicine for their healthcare assistance.•We have to learn the lessons regarding healthcare assistance during this pandemic to promote virtual assistance and support in the future.
To analyse the effects of confinement among people with type 1 diabetes (T1D) and their caregivers over the course of the COVID-19 crisis and to evaluate contemporary changes in medical assistance and patient preferences.
An observational cross-sectional study designed as a self-reported web-based survey was conducted over the course of the COVID-19 pandemic.
A total of 769 subjects participated in the survey (603 people with T1D and 166 caregivers). Changes in glycaemic control were reported in 66% of cases, weight gain in 40.4% of cases and decreased exercise levels in 65.4% of cases. Of the cohort, 53% maintained contact with the healthcare team, and 23% received specific information related to COVID-19. Emotional support was requested by 17% of respondents. Regarding telemedicine, 97.9% agreed with its use with the following preferences regarding the future: telephone call (84.5%), video-call (60.6%) and platform devices (39.7%).
Over the course of the COVID-19 pandemic, at least two-thirds of people with T1D underwent changes in the management of their condition. Almost all participants agreed with the concept of telemedicine, favouring telephone and video calls as their preferred means of communication.
Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and ...vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM).
We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years).
Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥ 42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 95% CI 0.561-2.586, P = 0.003) and IMT (β = 0.330 14.237-67.693, P = 0.003) were positively correlated with sclerostin.
Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.
•Ascorbic acid content is increased in roots of the Al-resistant cultivars under Al treatment.•Aluminum treatment increased the exudation of oxalic acid in Al-resistant cultivars.•The NADP-MDH ...activation state is increased for the effect of the aluminum in roots and leaves of Al-resistant cultivars.•Aluminum affects the expression levels of enzymes of the TCA cycle in cultivars of highbush blueberry.
Aluminum (Al) is an important factor that limits plant growth under acidic soil conditions. However, several plant species developed distinct mechanisms that limit the damage caused by high Al concentrations. In highbush blueberry (Vaccinium corymbosum), the Al resistance mechanisms are not fully understood. This study was designed to evaluate the effect of Al toxicity on roots and leaves of highbush blueberry genotypes with contrasting Al resistance Star (Al-sensitive) and Camellia and Cargo (Al-resistant) and identify the main molecular and physiological strategies underpinning adaptive Al stress responses in nutrient solution. After 48 h of Al treatment, the reduced form of ascorbate (ASC) was higher in roots, but unchanged in leaves of Cargo and Camellia genotypes compared to the control. We also observed decreased root exudation of oxalate in the Al-treated sensitive cultivar Star throughout the treatment period. However, in the resistant cultivar (Camellia), the exudation of oxalate increased 2.4- and 2.8-fold at 24 and 48 h, respectively. Al treatment differentially affected the enzyme activity and gene expression of the tricarboxylic acid (TCA) cycle enzymes. NAD-dependent malate dehydrogenase (NAD-MDH) expression in roots of cultivar Cargo was reduced at 24 h and increased at 48 h, whereas in leaves the expression was higher at 24 h and decreased at 48 h compared to the control. Citrate synthase (CS) activity in Al-resistant Cargo roots diminished at 24 h, increasing afterwards, without variation in the CS gene expression, compared with the initial time point (t = 0). In Al-resistant Camellia roots, the gene expression and the activity of CS decreased during Al exposure. NADP-dependent malate dehydrogenase (NADP-MDH) activity showed increased activity and gene expression at 24 h, in the leaves of cultivar Cargo, whereas in roots the gene expression decreased, but the activation state of NADP-MDH increased. The expression of genes encoding TCA cycle enzymes did not differ significantly in the Al-sensitive cultivar Star during Al exposure. In conclusion, the exudation of organic acid anions, particularly oxalate, plays an important role in Al resistance of highbush blueberry genotypes whilst elevated levels of ASC in roots, also contribute to the Al-resistance mechanisms exhibited by genotypes Camellia and Cargo.
Myostatin and irisin are two myokines related to energy metabolism, acting on skeletal muscle and recently suggested on adipose tissue in mice. However, the exact role of these myokines in humans has ...not been fully established. Our aim was to evaluate the relationship between serum levels of myostatin and irisin in type 2 diabetes mellitus patients and non-diabetic controls and to explore its links with metabolic parameters. Case–control study including 73 type 2 diabetes mellitus patients and 55 non-diabetic subjects as control group. Circulating myostatin and irisin levels were measured by enzyme-linked immunosorbent assays. Type 2 diabetes mellitus patients showed significantly lower myostatin levels (
p
= 0.001) and higher irisin levels (
p
= 0.036) than controls. An inverse relationship was observed between myostatin and irisin levels (
p
= 0.002). Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder factors, myostatin was negatively related to fasting plasma glucose (
p
= 0.005) and to triglyceride levels (
p
= 0.028) while irisin showed a positive association with these variables (
p
= 0.017 and
p
= 0.006 respectively). A linear regression analysis showed that irisin and fasting plasma glucose levels were independently associated to myostatin levels and that myostatin and triglyceride levels were independently associated to irisin concentrations in type 2 diabetes mellitus patients. Our results suggest that serum levels of myostatin and irisin are related in patients with type 2 diabetes. Triglyceride and glucose levels could modulate myostatin and irisin concentrations as a compensatory mechanism to improve the metabolic state in these patients although further studies are needed to elucidate whether the action of these myokines represents an adaptative response.
Long non-coding RNAs (lncRNAs) are non-coding RNAs longer than 200 nucleotides with dynamic regulatory functions. They interact with a wide range of molecules such as DNA, RNA, and proteins to ...modulate diverse cellular functions through several mechanisms and, if deregulated, they can lead to cancer development and progression. Recently, it has been described that lncRNAs are susceptible to form gene fusions with mRNAs or other lncRNAs, breaking the paradigm of gene fusions consisting mainly of protein-coding genes. However, their biological significance in the tumor phenotype is still uncertain. Therefore, their recent identification opens a new line of research to study their biological role in tumorigenesis, and their potential as biomarkers with clinical relevance or as therapeutic targets. The present study aimed to review the lncRNA fusions identified so far and to know which of them have been associated with a potential function. We address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window in cancer.
ABSTRACT
We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost ...every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.
Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim ...of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients.
•An improvement in hospitalizations related to diabetes in Spain in the period 2007–2015 was found.•We also observed a decrease in the frequentation rate and in the average length of stay.•A ...potential explanation is quality improvements in ambulatory management of diabetes.•We found differences in inpatient management, both at the hospital and the regional level.
To analyze the trends on diabetes mellitus (DM) healthcare management in Spain.
Retrospective observational study between January 1st 2007 and 31th December 2015 with DM as the principal diagnosis. The main clinical outcome measures were all-cause, in-hospital mortality and 30-day readmissions. We also analyze three Prevention Quality Indicators (PQI) for DM.
The number of hospitalization episodes decreased significantly as well as the frequentation rate and average length of stay (Incidence Rate Ratio IRR = 0.963, p < 0.001; 0.91, p < 0.001 and 0.986, p < 0.001, respectively). Crude in-hospital mortality and readmissions rates and risk-standardized in-hospital mortality rates (RSMR), however, remained stable (IRR = 0.988, p = 0.073; IRR = 1.003, p = 0.334 and IRR = 0.997, p = 0.116, respectively). A relevant variability in RSMR, both at hospital (Median Odds Ratio 1.49) and regional level, was found. High volume hospitals (≥105 DM discharges at year) showed better outcomes. High variability was also found in PQI indicators al regional level.
The present analysis shows an improvement in hospitalizations related to DM in Spain in the period 2007–2015. There was also a decrease in the frequentation rate and in the average length of stay. These findings are probably explained by quality improvements in the healthcare management of the DM at the ambulatory level. However, there were important differences in the management of diabetic inpatients both at the hospital and the regional level.