Consenso sobre la detección y el manejo de la prediabetes. Grupo de trabajo de consensos y guías clínicas de la Sociedad Española de Diabetes

En España, según datos del estudio [email protected], un 13,8% de la población adulta padece diabetes y un 14,8% algún tipo de prediabetes (intolerancia a la glucosa, glucemia basal alterada o ambas). Puesto que la detección precoz de la prediabetes puede facilitar la puesta en marcha de medidas terapéuticas que eviten su progresión a diabetes, consideramos que las estrategias de prevención en las consultas de atención primaria y especializada deberían consensuarse. La detección de diabetes y prediabetes mediante un cuestionario específico (test de FINDRISC) y/o la determinación de la glucemia basal en pacientes de riesgo permiten detectar los pacientes con riesgo de desarrollar la enfermedad y es necesario considerar cómo debe ser su manejo clínico. La intervención sobre los estilos de vida puede reducir la progresión a diabetes o hacer retroceder un estado prediabético a la normalidad y es una intervención coste-efectiva. Algunos fármacos, como la metformina, también se han mostrado eficaces en reducir la progresión a diabetes aunque no son superiores a las in tervenciones no farmacológicas. Finalmente, aunque no hay pruebas sólidas que apoyen la eficacia del cribado en términos de morbimortalidad, sí que ha observado una mejora de los factores de riesgo cardiovascular.El Grupo de Trabajo de Consensos y Guías Clínicas de la Sociedad Española de Diabetes (SED) ha elaborado unas recomendaciones que han sido consensuadas con la Sociedad Española de Endocrinología y Nutrición (SEEN), la Sociedad Española de Endocrinología Pediátrica (SEEP), la Sociedad Española de Farmacia Familiar y Comunitaria (SEFAC), la Sociedad Española de Medicina Familiar y Comunitaria (SEMFYC), la Sociedad Española de Médicos Generales (SEMG), la Sociedad Española de Médicos de Atención Primaria (SEMERGEN), la Sociedad Española de Medicina Interna (SEMI), la Asociación de Enfermería Comunitaria (AEC) y la Red de Grupos de Estudio de la Diabetes en Atención Primaria (RedGDPS)

Guía clínica de atención a menores transexuales, transgéneros y de género diverso

Transgénero; Terapia hormonal cruzada; Identidad de géneroTransgender; Hormone cross therapy; Gender identityTransgènere; Teràpia hormonal creuada; Identitat de gènereSome people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social–familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation.Algunas personas, también las menores de edad, tienen una identidad de género que no se corresponde con el sexo asignado al nacer. Se les conoce como personas trans*, que es el término paraguas que engloba transgénero, transexual y otras identidades no conformes con el género asignado. Las unidades de asistencia sanitaria a menores trans* requieren un trabajo multidisciplinario, realizado por personal experto en identidad de género, que permita, cuando así lo soliciten, intervenciones para el menor y su entorno sociofamiliar, de forma individualizada y flexible durante el camino de afirmación de género. Este modelo de servicio también incluye tratamientos hormonales adaptados en la medida de lo posible a las necesidades del individuo, más allá de los objetivos dicotómicos de un modelo binario tradicional. Esta guía aborda los aspectos generales de la atención profesional de menores trans* y presenta el protocolo actual basado en evidencia de tratamientos hormonales para adolescentes trans* y no binarios. Además, detalla aspectos clave relacionados con los cambios corporales esperados y sus posibles efectos secundarios, así como el asesoramiento previo sobre preservación de la fertilidad

Fatty Acid Profile of Mature Red Blood Cell Membranes and Dietary Intake as a New Approach to Characterize Children with Overweight and Obesity

Obesity is a chronic metabolic disease of high complexity and of multifactorial origin. Understanding the effects of nutrition on childhood obesity metabolism remains a challenge. The aim of this study was to determine the fatty acid (FA) profile of red blood cell (RBC) membranes as a comprehensive biomarker of children's obesity metabolism, together with the evaluation of their dietary intake. An observational study was carried out on 209 children (107 healthy controls, 41 who were overweight and 61 with obesity) between 6 and 16 years of age. Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ) and the Mediterranean Diet Quality Index for children (KIDMED) test. Compared to children with normal weight, children with obesity showed an inflammatory profile in mature RBC FAs, evidenced by higher levels of omega-6 polyunsaturated FAs (mainly arachidonic acid, p < 0.001). Children who were overweight or obese presented lower levels of monounsaturated FA (MUFA) compared to children with normal weight (p = 0.001 and p = 0.03, respectively), resulting in an increased saturated fatty acid (SFA)/MUFA ratio. A lower intake of nuts was observed for children with obesity. A comprehensive membrane lipidomic profile approach in children with obesity will contribute to a better understanding of the metabolic differences present in these individuals.This work was supported by the Department of Environment: Territorial Planning: Agriculture and Fisheries of the Basque Country Government (ELKARTEK 2017: and Innovation Fund 2017); the Department of Health of the Basque Government (2017222033: OBESIA 2016-2019); the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation under the grant agreement: TECNOMIFOOD project (CER-20191010); the INC (INTERNATIONAL NUT AND DRIED FRUIT COUNCIL) under the grant agreement OBINUT project (2016(II)-R01)

FACTORES DE RIESGO DE DIABETES EN UNA POBLACIÓN ADOLESCENTE DE CANGAS DE MORRAZO (GALICIA) (RIVACANGAS)

RESUMEN Objetivos Identificar factores de riesgo de desarrollar diabetes (DM) en una muestra de escolares. Material y método Estudio epidemiológico, transversal, multicéntrico en alumnos de la ESO (12-17 años) de 4 centros escolares de Cangas do Morrazo (Pontevedra). Variables: edad, sexo, antecedentes personales y familiares de DM, peso, estatura, perímetro de cintura (PC), índice cintura/talla (ICT), índice de masa corporal (IMC), presión arterial. Cuestionario de riesgo de DM para niños y adolescentes (Findrisc-A) (modificado), características de la dieta (Kidmed) y de la actividad física (PAQ-A). Resultados 630 escolares, 628 sin diabetes: 294 niñas (46,8%) y 334 niños (53,2%), media de edad 13,8±1,4 años. El 7,1% hipercolesterolemia; 1,7% ECV, 0,8% HTA y 0,3% DM. El 5,6% antecedentes familiares de 1er grado de DM. Antecedentes de 2º grado de DM el 18,6%. Sobrepeso el 23,3%. El 7,5% con obesidad central (PC >P90). El 21,0 % ICT >0,5. El 63,9% PAS >P90 y 23,7% PAD >P90. La puntuación media del Kidmed fue de 5,0±2,2. 21,7% con adherencia baja (8 puntos). Puntuación media PAQ-A de 2,6±0,7, mayor en niños (2,8±0,7 vs 2,5±0,7; p<0,001), con actividad física baja 1,6% y con actividad física alta el 19,4%. Puntuación media Findrisc-A 6,0±3,4. Relación directa entre Findrisc-A y PAS, PAD, PC, IMC e ICT. Inversa con Kidmed y PAQ-A. Conclusiones El riesgo medio de diabetes resultó bajo, aunque más del 10% presentaba riesgo alto o muy alto. Uno de cada cuatro tiene exceso de peso y uno de cada diez, obesidad. Palabras clave: Factores de riesgo. Adolescentes. Diabetes. Dieta. Actividad física.     ABSTRACT Objectives Identify factors of risk of developing diabetes (DM) in a sample of school. Materials and methods Epidemiologic study, transversal, multicenter in students (12-17 years) of four schools of Cangas do Morrazo (Pontevedra). Variables: age, sex, personal and family history of DM, weight, height, waist circumference (WC), waist/hight index (WHI), body mass index (BMI), blood pressure. Risk of DM questionnaire for children and adolescents (Findrisc-A) (modified), diet (Kidmed) and physical activity (PAQ-A). Results 630 school, 628 without diabetes: 294 girls (46.8%) and 334 children (53.2%), mean of age 13,8±1,4 years. 7.1% hypercholesterolemia; 1.7% CVD, hypertension 0.8% and 0.3% DM. 5.6% 1st degree of family history of DM. 2nd degree of family history of DM, 18.6%. 23.3% overweight. 7.5% with central obesity (PC>P90). 21.0% WHI>0.5. 63.9% SBP>P90 and 23.7% DBO>P90.  The average of the Kidmed score was 5.0±2.2. 21.7% with low adherence (8 points). PAQ-A mean score was 2.6±0.7, higher in children (2.8±0.7 vs 2.5±0.7; p<0.001), with low physical activity 1.6% and 19.4% high physical activity. Findrisc mean score 6.0±3.4. Relationship directly between Findrisc-A and SBP, DBP, WC, BMI and WHI. Reverse with Kidmed and PAQ-A. Conclusions The average diabetes risk was low, but more than 10% had high or very high risk. One in four is overweight and one of ten, obesity. Keywords: Risk factors. Adolescents. Diabetes. Diet. Physical activity

FACTORES DE RIESGO DE DIABETES EN UNA POBLACIÓN ADOLESCENTE DE CANGAS DE MORRAZO (GALICIA) (RIVACANGAS)

RESUMEN Objetivos Identificar factores de riesgo de desarrollar diabetes (DM) en una muestra de escolares. Material y método Estudio epidemiológico, transversal, multicéntrico en alumnos de la ESO (12-17 años) de 4 centros escolares de Cangas do Morrazo (Pontevedra). Variables: edad, sexo, antecedentes personales y familiares de DM, peso, estatura, perímetro de cintura (PC), índice cintura/talla (ICT), índice de masa corporal (IMC), presión arterial. Cuestionario de riesgo de DM para niños y adolescentes (Findrisc-A) (modificado), características de la dieta (Kidmed) y de la actividad física (PAQ-A). Resultados 630 escolares, 628 sin diabetes: 294 niñas (46,8%) y 334 niños (53,2%), media de edad 13,8±1,4 años. El 7,1% hipercolesterolemia; 1,7% ECV, 0,8% HTA y 0,3% DM. El 5,6% antecedentes familiares de 1er grado de DM. Antecedentes de 2º grado de DM el 18,6%. Sobrepeso el 23,3%. El 7,5% con obesidad central (PC >P90). El 21,0 % ICT >0,5. El 63,9% PAS >P90 y 23,7% PAD >P90. La puntuación media del Kidmed fue de 5,0±2,2. 21,7% con adherencia baja (8 puntos). Puntuación media PAQ-A de 2,6±0,7, mayor en niños (2,8±0,7 vs 2,5±0,7; p<0,001), con actividad física baja 1,6% y con actividad física alta el 19,4%. Puntuación media Findrisc-A 6,0±3,4. Relación directa entre Findrisc-A y PAS, PAD, PC, IMC e ICT. Inversa con Kidmed y PAQ-A. Conclusiones El riesgo medio de diabetes resultó bajo, aunque más del 10% presentaba riesgo alto o muy alto. Uno de cada cuatro tiene exceso de peso y uno de cada diez, obesidad. Palabras clave: Factores de riesgo. Adolescentes. Diabetes. Dieta. Actividad física.     ABSTRACT Objectives Identify factors of risk of developing diabetes (DM) in a sample of school. Materials and methods Epidemiologic study, transversal, multicenter in students (12-17 years) of four schools of Cangas do Morrazo (Pontevedra). Variables: age, sex, personal and family history of DM, weight, height, waist circumference (WC), waist/hight index (WHI), body mass index (BMI), blood pressure. Risk of DM questionnaire for children and adolescents (Findrisc-A) (modified), diet (Kidmed) and physical activity (PAQ-A). Results 630 school, 628 without diabetes: 294 girls (46.8%) and 334 children (53.2%), mean of age 13,8±1,4 years. 7.1% hypercholesterolemia; 1.7% CVD, hypertension 0.8% and 0.3% DM. 5.6% 1st degree of family history of DM. 2nd degree of family history of DM, 18.6%. 23.3% overweight. 7.5% with central obesity (PC>P90). 21.0% WHI>0.5. 63.9% SBP>P90 and 23.7% DBO>P90.  The average of the Kidmed score was 5.0±2.2. 21.7% with low adherence (8 points). PAQ-A mean score was 2.6±0.7, higher in children (2.8±0.7 vs 2.5±0.7; p<0.001), with low physical activity 1.6% and 19.4% high physical activity. Findrisc mean score 6.0±3.4. Relationship directly between Findrisc-A and SBP, DBP, WC, BMI and WHI. Reverse with Kidmed and PAQ-A. Conclusions The average diabetes risk was low, but more than 10% had high or very high risk. One in four is overweight and one of ten, obesity. Keywords: Risk factors. Adolescents. Diabetes. Diet. Physical activity

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

[Objective] Pituitary adenomas (PA) are rare in young patients, and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients.[Design] Clinical and molecular analysis of 235 patients (age ≤ 30 years) with PA. Clinicians from several Spanish and Chilean hospitals provided data.[Methods] Genetic screening was performed via next-generation sequencing and comparative genomic hybridization array. Clinical variables were compared among paediatric, adolescent (<19 years) and young adults’ (≥19–30 years) cohorts and types of adenomas. Phenotype–genotype associations were examined.[Results] Among the total cohort, mean age was 17.3 years. Local mass effect symptoms were present in 22.0%, and prolactinomas were the most frequent (44.7%). Disease-causing germline variants were identified in 22 individuals (9.3%), more exactly in 13.1 and 4.7% of the populations aged between 0–19 and 19–30 years, respectively; genetically positive patients were younger at diagnosis and had larger tumour size. Healthy family carriers were also identified.[Conclusions] Variants in genes associated with syndromic forms of PAs were detected in a large cohort of apparently sporadic pituitary tumours. We have identified novel variants in well-known genes and set the possibility of incomplete disease penetrance in carriers of MEN1 alterations or a limited clinical expression of the syndrome. Despite the low penetrance observed, screening of AIP and MEN1 variants in young patients and relatives is of clinical value.Peer reviewe

Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.Gly146Ala variant is common in individuals with a DSD and has been suggested to act as a susceptibility factor for adrenal disease or cryptorchidism. Since the allele frequency is high in the general population, and the functional testing of the p.Gly146Ala variant revealed inconclusive results, the disease-causing effect of this variant has been questioned. However, a role as a disease modifier is still possible given that oligogenic inheritance has been described in patients with NR5A1/SF-1 variants. Therefore, we performed next generation sequencing (NGS) in 13 DSD individuals harboring the NR5A1/SF-1 p.Gly146Ala variant to search for other DSD-causing variants and clarify the function of this variant for the phenotype of the carriers. Panel and whole-exome sequencing was performed, and data were analyzed with a filtering algorithm for detecting variants in NR5A1- and DSD-related genes. The phenotype of the studied individuals ranged from scrotal hypospadias and ambiguous genitalia in 46,XY DSD to opposite sex in both 46,XY and 46,XX. In nine subjects we identified either a clearly pathogenic DSD gene variant (e.g. in AR) or one to four potentially deleterious variants that likely explain the observed phenotype alone (e.g. in FGFR3, CHD7). Our study shows that most individuals carrying the NR5A1/SF-1 p.Gly146Ala variant, harbor at least one other deleterious gene variant which can explain the DSD phenotype. This finding confirms that the NR5A1/SF-1 p.Gly146Ala variant may not contribute to the pathogenesis of DSD and qualifies as a benign polymorphism. Thus, individuals, in whom the NR5A1/SF-1 p.Gly146Ala gene variant has been identified as the underlying genetic cause for their DSD in the past, should be re-evaluated with a NGS method to reveal the real genetic diagnosis

Rare Germline DICER1 Variants in Pediatric Patients With Cushing's Disease: What Is Their Role?

Context: The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the DICER1 gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD). The role of DICER1 in other corticotropinomas, however, remains unknown. Objective: To perform a comprehensive screening for DICER1 variants in a large cohort of CD patients, and to analyze their possible contribution to the phenotype. Design, setting, patients, and interventions: We included 192CD cases: ten young-onset (age <30 years at diagnosis) patients were studied using a next generation sequencing panel, and 182 patients (170 pediatric and 12 adults) were screened via whole-exome sequencing. In seven cases, tumor samples were analyzed by Sanger sequencing. Results: Rare germline DICER1 variants were found in seven pediatric patients with no other known disease-associated germline defects or somatic DICER1 second hits. By immunohistochemistry, DICER1 showed nuclear localization in 5/6 patients. Variant transmission from one of the parents was confirmed in 5/7 cases. One patient had a multinodular goiter; another had a family history of melanoma; no other patients had a history of neoplasms. Conclusions: Our findings suggest that DICER1 gene variants may contribute to the pathogenesis of non-syndromic corticotropinomas. Clarifying whether DICER1 loss-of-function is disease-causative or a mere disease-modifier in this setting, requires further studies.This work was supported by the Intramural Research Programs of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute for Neurological Diseases and Stroke, National Institutes of Health, a grant from the Basque Department of Education (IT795-13), a grant from the Basque Department of Health (GV2018111082), the Merck Serono Research award from Fundacion Salud 2000 (15-EP-004) and the Jose Igea 2018 grant, sponsored by Pfizer, from Fundacion Sociedad Espanola de Endocrinologia Pediatrica (SEEP)

Genetic profile of a large Spanish cohort with hypercalcemia

IntroductionThe disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they are expressed are nonspecific or present only as a laboratory finding, usually hypercalcemia. Because many of these disorders have a genetic etiology, in the present study, we sequenced a selection of 55 genes encoding the principal proteins involved in the regulation of calcium metabolism.MethodsA cohort of 79 patients with hypercalcemia were analyzed by next-generation sequencing.ResultsThe 30% of our cohort presented one pathogenic or likely pathogenic variant in genes associated with hypercalcemia. We confirmed the clinical diagnosis of 17 patients with hypocalciuric hypercalcemia (pathogenic or likely pathogenic variants in the CASR and AP2S1 genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the CASR gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the CYP24A1 gene). However, we also found variants in genes associated with primary hyperparathyroidism (GCM2), renal hypophosphatemia with or without rickets (SLC34A1, SLC34A3, SLC9A3R1, VDR, and CYP27B1), DiGeorge syndrome (TBX1 and NEBL), and hypophosphatasia (ALPL). Our genetic study revealed 11 novel variants.ConclusionsOur study demonstrates the importance of genetic analysis through massive sequencing to obtain a clinical diagnosis of certainty. The identification of patients with a genetic cause is important for the appropriate treatment and identification of family members at risk of the disease

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p