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

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

Relationship between malnutrition and the presence of symptoms of anxiety and depression in hospitalized cancer patients

Background Anxiety and depression are a common issue in patients with cancer, yet understudied among hospitalized patients. The aim of this study was to estimate the prevalence of anxiety and depression symptomatology in cancer inpatients and its relationship with malnutrition. Methods Cross-sectional study in hospitalized cancer patients. A nutritional assessment was done using the Global Leadership Initiative on Malnutrition (GLIM) criteria to diagnose malnutrition. Data regarding anxiety and depression symptomatology was obtained with the Hospital Anxiety and Depression Scale (HADS). Results A total of 282 inpatients were assessed. GLIM criteria found 20% (66) of well-nourished and 80% (216) with malnutrition. HADS presented an average score of 8.3±4.4 with respect to anxiety and an average score of 7.7±4.6 with respect to depression. Up to 54% of the patients showed a possible presence of anxiety, and 45.3% of them showed a possible presence of depression. In malnourished patients, HADS score was non-signifcantly higher with respect to anxiety (8.5±4.3 in malnourished vs 7.1±4.6 in well-nourished; p=0.06) and was signifcantly higher with respect to depression (8.2±4.6 in malnourished vs 5.3±4.0 in well-nourished; p<0.001). After controlling for potential confounders, malnourished patients were 1.98 times more likely to present anxious symptomatology (95% CI 1.01–3.98; p=0.049) and 6.29 times more likely to present depressive symptomatology (95% CI 1.73–20.47; p=0.005). Conclusions The presence of anxiety and depression symptomatology in oncological inpatients is high. There is an association between malnutrition and presenting anxious and depressive symptomatology in hospitalized cancer patientsThis research was funded in part by the 2017 research grants of SAEDYN (Sociedad Andaluza de Endocrinología, Diabetes y Nutrición) and SANCYD (Sociedad Andaluza de Nutrición Clínica y Dietética) and an unrestricted grant from Abbott Laboratories SA (Spain). V.C.-B. is funded by postdoctoral fellowships from the Junta de Andalucía (RH-0141–2020). Funding for open access charge: Universidad de Málaga/CBUA

Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases

Objectives: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. Methods: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 – December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal- 5′-phosphate (PLP) and genetic study of ALPL gene. Results: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). Conclusions: This new algorithm was effective in detecting previously undiagnosed cases ofHPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.Instituto de Salud Carlos III grants PI21-01069 co-funded by the European Regional Development Fund (FEDER) and by Junta de Andalucía grant PI-0268-2019Operational Programme for Youth Employment of the Junta de Andalucía with Ref: POEJ_04/2022-12Instituto de Salud Carlos III with co-funding by FEDER (CD20/00022)(FI19/00118 and CM21/00221) from Instituto de Salud CarlosPostdoctoral fellowship from the Junta de Andalucía (RH-0141-2020

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene

IntroductionHypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease.MethodsPatients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry.ResultsTwo previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T&gt;C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction.ConclusionsThe two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 9

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, volumen 9, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Oral Nutritional Supplements in Adults with Cystic Fibrosis: Effects on Intake, Levels of Fat-Soluble Vitamins, and Bone Remodeling Biomarkers

Background: The use of oral nutritional supplements (ONS) is common practice in patients suffering from cystic fibrosis (CF). We aimed to describe the rate of ONS use to assess their contribution to dietary intake and to determine if they are associated with respiratory status, body composition, muscle strength, bone mineral density (BMD), bone remodeling biomarkers, and plasmatic levels of vitamins. Methods: Cross-sectional study. Patients were clinically stable adults recruited from the CF unit. A 4-day prospective dietary questionnaire was conducted; in addition to respiratory variables, body composition, and BMD (through densitometry, DXA), muscle strength (JAMAR dynamometer), fat-soluble vitamins, and bone remodeling biomarkers (vitamins A, D, and E; osteocalcin, OC; undercarboxylated osteocalcin, ucOC; degradation of the C-terminal telopeptides of type I collagen, CTX; and receptor activator of nuclear factor-kappaB ligand, RANKL) were also evaluated. Results: The study included 59 subjects with CF (57.6% female, mean age 29.3 ± 9.4 years, and BMI 22.0 ± 3.6 kg/m2). In this study, 22% (13) patients were taking ONS and presented, compared with those not taking them, significantly more total and mild exacerbations and lower BMI; moreover, they showed a significantly higher total daily calorie intake in addition to a higher consumption of carbohydrates, proteins, and lipids per kg of body weight, omega-3 fatty acids, and vitamins A, D, and E. Vitamin E plasmatic levels were significantly higher in the group on ONS, as was the case with RANKL; finally, a lower rate of vitamin D deficiency was also found. Conclusions: ONS were used by patients with worse respiratory and nutritional statuses and their use was associated with a higher intake of macro- and micronutrients and with better plasmatic levels of fat-soluble vitamins

Prevalence of Sarcopenia and Dynapenia and Related Clinical Outcomes in Patients with Type 1 Diabetes Mellitus

Background: Sarcopenia has recently been recognized as a complication of diabetes. However, there are few results about the prevalence of sarcopenia and dynapenia and the related clinical outcomes in type 1 diabetes mellitus (T1DM). Our objectives were to evaluate the prevalence of sarcopenia and dynapenia and to determine whether there are any associations with disease-related factors in people with T1DM. Methods: A cross-sectional study was conducted in people with T1DM. We assessed appendicular skeletal mass index (ASMI) using bioimpedance 50 Hz (Nutrilab Akern). Muscle function was assessed through handgrip strength (HGS) using a Jamar dynamometer. Sarcopenia was defined as a low HGS with low ASMI, whereas dynapenia was defined as low HGS with a normal ASMI. We used HGS data from the Spanish population percentile table and a cut-off point at p5 as dynapenia. The association of clinical, metabolic, and lifestyle variables with sarcopenia and dynapenia was studied. Results: This study included 62 T1DM patients (66% females, mean age of 38 ± 14 years, body mass index (BMI) of 24.9 ± 4.7 kg/m2). The prevalence of sarcopenia and dynapenia was 8% and 23%, respectively. In our sample, there were more men in the sarcopenic and dynapenic groups. The sarcopenic group showed a significantly higher mean HbA1c value. Lower diabetes duration, PREDIMED score, BMI, and muscle mass measures (fat-free mass index (FFMI), ASMI, and body cell mass index (BCMI)) were significantly associated with sarcopenia. Decreased diabetes duration, PREDIMED score, phase angle (PhA), and HGS values showed a significant association with dynapenia. Conclusions: The prevalence of sarcopenia and dynapenia was high in people with T1DM in our study. Specifically, the proportion of dynapenia was quite high. HGS and ASMI are practical tools for the assessment of muscle health status in T1DM, and low values are associated with poor glycemic control, underweight, and low adherence to the Mediterranean diet. Thus, dynapenia may predict accelerated muscle aging in T1DM.Pre-doctoral fellowship from Instituto de Investigación Biosanitaria de Granada (Ibs. Granada) (74-2022)Postdoctoral fellowship from Junta de Andalucia (RH-0141-2020

Prevalence of Sarcopenia and Dynapenia and Related Clinical Outcomes in Patients with Type 1 Diabetes Mellitus

Background: Sarcopenia has recently been recognized as a complication of diabetes. However, there are few results about the prevalence of sarcopenia and dynapenia and the related clinical outcomes in type 1 diabetes mellitus (T1DM). Our objectives were to evaluate the prevalence of sarcopenia and dynapenia and to determine whether there are any associations with disease-related factors in people with T1DM. Methods: A cross-sectional study was conducted in people with T1DM. We assessed appendicular skeletal mass index (ASMI) using bioimpedance 50 Hz (Nutrilab Akern). Muscle function was assessed through handgrip strength (HGS) using a Jamar dynamometer. Sarcopenia was defined as a low HGS with low ASMI, whereas dynapenia was defined as low HGS with a normal ASMI. We used HGS data from the Spanish population percentile table and a cut-off point at p5 as dynapenia. The association of clinical, metabolic, and lifestyle variables with sarcopenia and dynapenia was studied. Results: This study included 62 T1DM patients (66% females, mean age of 38 ± 14 years, body mass index (BMI) of 24.9 ± 4.7 kg/m2). The prevalence of sarcopenia and dynapenia was 8% and 23%, respectively. In our sample, there were more men in the sarcopenic and dynapenic groups. The sarcopenic group showed a significantly higher mean HbA1c value. Lower diabetes duration, PREDIMED score, BMI, and muscle mass measures (fat-free mass index (FFMI), ASMI, and body cell mass index (BCMI)) were significantly associated with sarcopenia. Decreased diabetes duration, PREDIMED score, phase angle (PhA), and HGS values showed a significant association with dynapenia. Conclusions: The prevalence of sarcopenia and dynapenia was high in people with T1DM in our study. Specifically, the proportion of dynapenia was quite high. HGS and ASMI are practical tools for the assessment of muscle health status in T1DM, and low values are associated with poor glycemic control, underweight, and low adherence to the Mediterranean diet. Thus, dynapenia may predict accelerated muscle aging in T1DM

Influence of the Mediterranean Diet on Healthy Aging

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologies that are associated with aging, in order to increase the quality of life of the aging population. In this review we analyze the influence of the Mediterranean diet on the molecular pathways and the microbiota associated with more favorable aging patterns, as well as its possible role as an anti-aging treatment.Postdoctoral fellowship from the Junta de Andalucia (RH-0141-2020)Postdoctoral fellowship from the Instituto de Salud Carlos III (CD20/00022