Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice

This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER) and Junta de Andalucia (PI-0268-2019). In addition, V.C.-B. and C.G.-F. are funded by postdoctoral fellowships from the Junta de Andalucia and Institute of Health Carlos III respectively (RH-0141-2020; CD20/00022).Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extraskeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.Institute of Health Carlos III grants PI18-00803 PI18-01235European Commission Junta de Andalucia PI-0268-2019Instituto de Salud Carlos III RH-0141-2020 CD20/0002

Obesity and Bone Health: A Complex Relationship

Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.Instituto de Salud Carlos IIIEuropean Commission CD20/00022 PI18-00803 PI21-01069 PI18-01235European CommissionJunta de Andalucia PI-0268-201

The Influence of the Mediterranean Dietary Pattern on Osteoporosis and Sarcopenia

Diet is a modifiable factor in bone and muscle health. The Mediterranean diet (MedDiet) is rich in nutrients and contains key bioactive components with probable protective effects on muscle and bone deterioration. Osteoporosis (OP) and sarcopenia are diseases that increase frailty and susceptibility to fracture, morbidity and mortality. Therefore, it is necessary to combat them in the population. In this regard, MedDiet adherence has proven to be beneficial to bone mineral density (BMD), muscle mass, physical function, OP and sarcopenia. Hence, this diet is proposed as a therapeutic tool that could slow the onset of osteoporosis and sarcopenia. However, there is doubt about the interaction between the MedDiet, strength and fracture risk. Perhaps the amount of EVOO (extra virgin olive oil), fruits, vegetables and fish rich in anti-inflammatory and antioxidant nutrients ingested has an influence, though the results remain controversiaInstitute of Health Carlos III grants (PI21-01069, PI18-01235 and CIBERFES)European Regional Development Fund (FEDER)Junta de Andalucía (PI- 0268-2019)Junta de Andalucía and Institute of Health Carlos III, respectively (RH-0141-2020; CD20/00022

Nutrients and Dietary Patterns Related to Osteoporosis

Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.Instituto de Salud Carlos III PI18/01235European Union (EU

Vitamin D Status, Calcium Intake and Risk of Developing Type 2 Diabetes: An Unresolved Issue

The relationship between vitamin D status, calcium intake and the risk of developing type 2 diabetes (T2D) is a topic of growing interest. One of the most interesting non-skeletal functions of vitamin D is its potential role in glucose homeostasis. This possible association is related to the secretion of insulin by pancreatic beta cells, insulin resistance in different tissues and its influence on systemic inflammation. However, despite multiple observational studies and several meta-analyses that have shown a positive association between circulating 25-hydroxyvitamin D concentrations and the risk of T2D, no randomized clinical trials supplementing with different doses of vitamin D have confirmed this hypothesis definitively. An important question is the identification of what 25-hydroxyvitamin D levels are necessary to influence glycemic homeostasis and the risk of developing T2D. These values of vitamin D can be significantly higher than vitamin D levels required for bone health, but the currently available data do not allow us to answer this question adequately. Furthermore, a large number of observational studies show that dairy consumption is linked to a lower risk of T2D, but the components responsible for this relationship are not well established. Therefore, the importance of calcium intake in the risk of developing T2D has not yet been established. Although there is a biological plausibility linking the status of vitamin D and calcium intake with the risk of T2D, well-designed randomized clinical trials are necessary to answer this important question

Exploring the Role of Sclerostin as a Biomarker of Cardiovascular Disease and Mortality: A Scoping Review

Sclerostin is most recognized for its role in controlling bone formation; however, it is also expressed in the heart, aorta, coronary, and peripheral arteries. Human studies have associated high circulating sclerostin levels with the presence of different cardiovascular diseases (CVD), surrogate CVD markers, and a high risk of cardiovascular events in some populations. However, this is still a matter of scientific debate, as the results have been very heterogeneous among studies. In the present review, the association between serum sclerostin levels and CVD and/or cardiovascular mortality was analyzed. For this purpose, a scoping review was performed in which articles measuring serum sclerostin levels and cardiovascular risk in patients were selected. Eleven articles answered the research question; of these articles, 8/11 evaluated the association between sclerostin and CVD, of which 4/8 found a positive association, 2/8 found a negative association, and 2/8 found no association between variables. Five (5/11) of the articles included in the study evaluated cardiovascular mortality, of which 3/5 found a positive association, 1/5 found a negative association, and 1/5 found no association between variables. In conclusion, we did not find sufficient results to be able to demonstrate an association between elevated sclerostin levels and the development of CVD and/or cardiovascular mortality in the general population due to heterogeneity in the results. However, there seems to be a tendency to consider increased sclerostin levels as a risk factor for both the development of cardiovascular events and cardiovascular mortality in specific populations. Further studies in this field will help to solve some of the inconsistencies found during this scoping review and allow for the future use of sclerostin measurement as a strategy in the prevention and diagnosis of CVD and/or cardiovascular mortality.Instituto de Salud Carlos III European Commission PI18-00803 PI21/01069 PI18-01235 CD20/00022European CommissionJunta de Andalucia PI-0268-2019 RH-0069-2021Instituto de Salud Carlos IIIUniversity of Granada FI19/00118European Commission 811

The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.Instituto de Salud Carlos III European Commission PI18-00803 PI21-01069 PI18-01235 CD20/00022 FI19/00118European CommissionJunta de Andalucia PI-0268-2019University of GranadaEuropean Commission 811

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and ucOC levels though the improvement of MetS risk factors. This bone protein appeared as a potential biomarker to classify CVR in the MetS population, especially for MetS patients without prevalent T2D. Furthermore, ucOC serum levels could be good predictors of T2D prevalence.Instituto de Salud Carlos III European Commission PI18-00803 PI21/01069 PI18-01235 FI19/00118 CD20/00022European CommissionJunta de Andalucia CD20/00022 PI-0268-2019 RH-0069202

Inclusive Assessment and Sustainability Dimensions: Pre-Service Teachers' Ideas and Knowledge

The eco-social crisis urges the transformation of teacher training programmes. It is imperative for educators to be able to respond to global challenges. This transformation involves working from new perspectives that integrate assessment processes focused on eco-social justice and inclusion from a broad perspective. Bearing this in mind, a training process focused on the theoretical construction of assessment practice from the perspective of Education for Sustainability and Inclusive Education was designed. It is framed within the context of the Master's Degree in Educational Research for Teachers' Professional Development. The study presented, which is of a qualitative and interpretative nature, focuses on knowing the impact of the process in the progression of the participating students' ideas and knowledge construction. The students' group work, two questionnaires of a different nature and a teaching journal, were used to collect data. Likewise, an ad hoc analysis system was developed that allowed transforming and interpreting the data obtained. The results show progress in the ideas and knowledge of the students in aspects related to the socio-environmental and ethical dimension of the assessment, integrating the principles of Education for Sustainability and Inclusive Education in the design of assessment activities in the classroom. The results reflect that the developed training process has influenced the complexity of the ideas of the students with regard to the content worked on. The proposal could hence serve as a reference for other training processes that have similar characteristics

Identificación de potenciales biomarcadores de calcificación vascular en pacientes con diabetes mellitus tipo 2 mediante el uso de herramientas bioinformáticas de libre acceso

Identificación de potenciales biomarcadores implicados en procesos de calcificación vascular para avanzar en el diagnóstico y tratamiento de esta patología en sus estadíos subclínicos. Resultados: Se identificaron 530 proteínas en las muestras analizadas con funciones mayoritariamente de unión a calcio y catalítica. 37 de ellas fueron comunes en otras patologías vasculares relacionadas. La exploración de las redes biológicas de las 37 proteínas identificadas, dio lugar a la identificación de 2 potenciales marcadores específicos de calcificación vascular en procesos ateroscleróticos, como la proteína mitocondrial de choque térmico de 10 kDa, y la subunidad flavoproteica de la succinato deshidrogenasa. Conclusiones: Existe una importante expresión de proteínas implicadas en procesos de mineralización ósea en tejido vascular calcificado, sugiriendo la existencia de mecanismos moleculares comunes entre la regulación ósea y vascular. El uso de herramientas bioinformáticas sugiere la implicación de la proteína de choque térmico de 10 kDa mitocondrial y la subunidad flavoproteica de la succinato deshidrogenasa como posibles biomarcadores de calcificación vascular en pacientes con DM2, aunque son necesarios estudios adicionales que confirmen esta hipótesis.El presente trabajo ha sido financiado a través de una beca de investigación de la FSEEN en la convocatoria 2016 y de un proyecto de la Junta de Andalucía (PI0207-2016)