Clinical report of Bosma arhinia microphthalmia syndrome with a new variant on SMCHD1 gene. A case report.

The Bosma syndrome (BAMS: Bosma arhinia microphthalmia syndrome) is a condition first described in 1972. Since then, several reviews have published the cases looking for diagnostic criteria and associated genetic alterations. The mutation in the SMCHD1 gene (Structural Maintenance of Chromosomes flexible Hinge Domain containing protein 1) seems to explain a part of the development of the phenotype. Not all cases show the same alterations or meet the classic diagnostic criteria, and few have undergone genetic analysis. We present a case with a new variant in this gene and an update of the literature on this syndrome with the aim of improving the diagnosis and follow-up of these patients.

Endocrine Adverse Events Related To Immune Checkpoint Inhibitor Treatment: Relationship Between Antibodies and Severity of Thyroid Dysfunction.

OBJECTIVE: The purpose of this study was to identify predictive and risk factors for the development of immune-related endocrinopathies and to analyze the incidence and characteristics of immune-related endocrinopathies in our population Design: A retrospective, single-centre cohort carried out at Gregorio Marañón Hospital between January 2018 -December 2019. METHODS: A total of 163 patients were enrolled. In January 2018 and December 2019, we treated patients who underwent ICI treatment in the Medical Oncology Department of General University Hospital Gregorio Marañón, a tertiary care public hospital in Madrid, as part of an observational, retrospective, single-center cohort study. RESULTS: Endocrinopathies were diagnosed in 19.5% of the patients (n=32). The tumours with the highest incidence of endocrinopathies were non-small cell lung cancer (25,9%), kidney cell cancer (25%) and hepatocarcinoma (20%). Among the 32 patients who developed endocrinopathy, 18,8%, 19,13%, and 21,28% received anti-CTLA-4, anti-PD-1 and anti-PDL-1, respectively. Thyroid dysfunction was the most frequent endocrinopathy (12,8%). A higher percentage of patients with negative antiTPO and antiTG antibodies developed G1 hypothyroidism compared to patients with positive antibodies who developed a higher proportion of G2 hypothyroidism. The presence of an initial phase of thyrotoxicity was not related to greater severity. We observed longer progression-free survival in patients who developed thyroid dysfunction. CONCLUSION: Pre-existing antibodies were independently associated with endocrinopathies. Moreover, our study let us conclude that the presence of thyroid autoantibodies may be related to its severity. It is important to determine anti-thyroid antibodies prior to the start of immunotherapy as a risk factor for thyroid dysfunction, which in turn is a prognostic marker.

Morphological, clinical, and functional efficacy in the short and medium-term after radiofrequency treatment of predominantly solid, large, and clinically relevant thyroid nodules in patients who are not candidates for surgery: The experience after 100 procedures.

INTRODUCTION: Thyroid nodules (TN) are a prevalent pathology that can generate morbidity, in which case the traditional treatment is usually surgery. OBJECTIVE: To analyse the efficacy of radiofrequency ablation (RFA) treatment as a therapeutic alternative in the combined clinical, morphological, and functional control of predominantly solid, benign and clinically relevant TNs in patients not subsidiary to surgery. MATERIALS AND METHODS: A descriptive, retrospective, case series study was carried out to assess the efficacy and safety of the use of RFA. According to medical criteria, the selected patients underwent a clinical, ultrasound, and biochemical assessment prior to the procedure and then after the procedure at 1, 3, 6, and 12 months and then every 6-12 months according to medical criteria. RESULTS: A total of 100 RFA were performed on 83 patients with 85 TNs of ≥2.5 cm with an initial volume (IV) of 21.48 ±â€¯15.89 ml. After a mean of 1.17 RFA sessions per TN, the volume decreased progressively and significantly (p < 0.01 for all times compared to the initial value), with a mean volume reduction rate (VRR) in relation to the IV of 54.43 ±â€¯19.56% at 1-month follow-up; 67.69 ±â€¯17% at 3 months; 70.38 ±â€¯15.46% at 6 months; 70.67 ±â€¯17.27% at 12 months and 70.24 ±â€¯17.7% at the last follow-up. 88% of the patients followed up >6 months achieved the combined objective of a volume reduction rate of more than 50% of the VI, thyroid normal function and absence of clinic; and in all of these, it was maintained until the final follow-up date. Acute complications (mostly mild and all transient) were reported in 9 of the 100 RFA performed. CONCLUSION: Our findings validate in our setting the efficacy and safety of RFA in predominantly large and solid TNs, and add undescribed information to position the technique more favourably as a therapeutic alternative.

Review of SGLT2i for the Treatment of Renal Complications: Experience in Patients with and Without T2D.

The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly benefit cardiac function through multifaceted interorgan cross talk, which can break the cardiorenal vicious circle linked to T2D. In this article, we briefly review the different mechanisms of action that may explain the renal beneficial effects of SGLT2i and disclose the results of the key renal outcome trials and the subsequent update of related clinical guidelines.

Inferior petrosal sinus sampling and stimulation with CRH: 15 years of experience in a tertiary hospital.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is indicated in the diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), especially when the results of the initial diagnostic tests are discordant. OBJECTIVE: To describe the patients who underwent this invasive functional test in a tertiary hospital. METHODS: This was an observational study of a retrospective cohort of patients with ACTH-dependent CS and IPSS between 2004 and 2019. We determined their epidemiological, hormonal, radiological and functional characteristics, and evaluated their diagnostic capacity and optimal cut-off points to differentiate between Cushing's disease (CD) and ectopic Cushing's syndrome (ECS). RESULTS: 23 patients were evaluated, of which 65.2% were women with the average age of 42 (36-62) years. ACTH secretion of pituitary origin was evident in 82.6% of the patients and of ectopic origin in 17.4%. Plasma cortisol, urinary free cortisol, and ACTH levels were higher in patients with ECS. Regarding IPSS, the baseline central/peripheral ACTH gradient detected 89.5% of patients with CD and after stimulation with CRH, 100%. The optimal cut-off points in the diagnosis of CD were 2.06 at baseline and 2.49 after CRH stimulation. CONCLUSION: IPSS with CRH stimulation is a test with a high diagnostic accuracy for correctly classifying patients with CD and ECS. The cut-off points of the gradients may be different from the classic ones. Therefore, we recommend that each center perform its own evaluation.

Asociación entre el cambio relativo de peso e índice de masa corporal con la función pulmonar en adolescentes y adultos con fibrosis quística: influencia del género y la diabetes / Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes

FUNDAMENTO: El estado nutricional es un indicador pronóstico en la fibrosis quística (CF). La prevención del deterioro nutricional y de la pérdida de peso son objetivos clínicos principales, ya que están asociados con empeoramiento de la función pulmonar y aumento de la mortalidad. Objetivo: Identificar si existe una relación entre los parámetros clínicos de nutrición, y sus cambios relativos, con la función pulmonar (FEV1%) en una cohorte de pacientes adolescentes y adultos con CF. Métodos: Analizamos de forma retrospectiva una serie de 64 pacientes mayores de 14 años. Se recogieron datos del peso, talla e IMC, suplementos nutricionales, y la función pulmonar en fase de estabilidad tanto en el año de realización del primer test de sobrecarga oral de glucosa (OGTT) patológico como en el año previo. Se determinaron los cambios relativos de peso e IMC, y su relación con FEV1%, mediante regresión lineal y ANOVA, así como la influencia del género y la diabetes. Resultados: La media de edad de la serie fue de 26,8 años (28 mujeres y 36 varones). El 26,7% tenían una tolerancia normal a la glucosa (TGN) y el 18,3% tenían diabetes sin alteración de la glucosa en ayunas (CFRD sin FPG). La media del IMC fue de 20,32, con un peso medio de 53,53 kg. El 32,8% tenían un IMC < 18,5 y tan solo el 4,7% presentaban sobrepeso. De forma global, un cambio relativo de peso positivo (≥ 6%) se asociaba con un incremento del FEV1% (9,31%) respecto a los que presentaban una mayor pérdida de peso, de al menos un 2%, los cuales tenían una caída del FEV1 del 12,09%. Los pacientes con CFRD sin FPG presentaban peor función pulmonar si mostraban una pérdida relativa de peso superior al 2%, en comparación con TGN. Conclusiones: En los pacientes con CF, la ganancia relativa de peso tiene una asociación positiva con el FEV1%, mientras que una pérdida ≥ 2% tiene una repercusión significativa negativa en la función pulmonar

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14 years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8 years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53 kg; 32.8% had BMI < 18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥ 6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function.

Clinical features, mortality, hospital admission, and length of stay of a cohort of adult patients with diabetic ketoacidosis attending the emergency room of a tertiary hospital in Spain / Características clínicas, mortalidad, hospitalización y duración de la estancia de pacientes adultos con cetoacidosis diabética admitidos en un servicio de urgencias de un hospital terciario en España

AIM: To assess the clinical features, length of stay, incidence rate, mortality, and hospital admissions of patients with episodes of diabetic ketoacidosis (DKA). PATIENTS: It was conducted retrospective, cross-sectional study of 164 consecutive admissions of adult patients (2008-August 2012), with type 1 or type 2 diabetes already known or new onset. RESULTS: Mortality rate was 1.2%. The DKA episodes were mild (18.9%), moderate (31.7%), or severe (49.4%). The cumulative incidence was 2.66 cases/1000 patients with diabetes (DM) in 4.5 years. The most common causes triggering DKA were infection (33.2%) and dietary transgression and/or insulin dose omission (30.7%). A total of 12.8% of patients had new onset DM, 56.7% type 1, and 26.8% type 2 DM. Patients with type 2 DM were older and had at admission higher creatinine, BUN, osmolality, sodium, and anion gap levels. Patients with new-onset of DM had higher levels of glucose and sodium, but lower potassium levels. No differences were found in pH or bicarbonate. Admission to the intensive care unit (ICU) was required in >50% of cases (p < 0.001), and 86.6% of patients were finally admitted to a medical ward (p = 0.005). The length of stay at the ICU (p < 0.001) and hospital (p = 0.013) was significantly different depending on DKA severity. CONCLUSIONS: Most DKA episodes require hospital admission, but mortality is <2%, and length of stay at the ER and medical ward depends on type of DM and initial severity of the episode

OBJETIVO: Se investigaron las características clínicas, la duración, la tasa de incidencia, la mortalidad y los ingresos de episodios de cetoacidosis diabética (CAD). PACIENTES: Se realizó un estudio retrospectivo, transversal, con 164 admisiones consecutivas de adultos (2008-agosto 2012), con diabetes (DM) tipo 1 y 2 ya conocida o debut diabético. RESULTADOS: La tasa de mortalidad fue del 1,2%. Los episodios de CAD fueron leves (18,9%), moderados (31,7%) y graves (49,4%). La incidencia acumulada fue de 2,66 casos/1.000 pacientes con DM en 4,5 años. Las causas desencadenantes más frecuentes fueron las infecciones (33,2%) y la transgresión dietética y/u omisión de la dosis de insulina (30,7%). El 12,8% tuvieron un debut diabético, 56,7% eran DM tipo 1 y el 26,8% tipo 2. Los casos con DM tipo 2 tenían mayor edad y presentaban al ingreso mayores niveles de creatinina, BUN, osmolaridad, sodio y anion GAP. El debut diabético presentaba niveles más elevados de glucosa y sodio, pero valores más bajos de potasio. No se encontró ninguna diferencia en el pH o bicarbonato. La admisión en la unidad de cuidados intensivos (UCI) se requirió en más del 50% de los casos (p < 0,001) y un 86,6% fue finalmente ingresado en una planta de hospitalización médica (p = 0,005). La duración de las estancias en la UCI (p < 0,001) y en el hospital (p = 0,013) fueron significativamente diferentes según la gravedad de la CAD. CONCLUSIONES: La mayoría de las crisis de CAD requieren de ingreso, pero la mortalidad es inferior al 2%, variando la duración de la estancia en urgencias y hospitalización dependiendo del tipo de DM y la gravedad inicial del episodio

Clinical features, mortality, hospital admission, and length of stay of a cohort of adult patients with diabetic ketoacidosis attending the emergency room of a tertiary hospital in Spain.

AIM: To assess the clinical features, length of stay, incidence rate, mortality, and hospital admissions of patients with episodes of diabetic ketoacidosis (DKA). PATIENTS: It was conducted retrospective, cross-sectional study of 164 consecutive admissions of adult patients (2008-August 2012), with type 1 or type 2 diabetes already known or new onset. RESULTS: Mortality rate was 1.2%. The DKA episodes were mild (18.9%), moderate (31.7%), or severe (49.4%). The cumulative incidence was 2.66 cases/1000 patients with diabetes (DM) in 4.5 years. The most common causes triggering DKA were infection (33.2%) and dietary transgression and/or insulin dose omission (30.7%). A total of 12.8% of patients had new onset DM, 56.7% type 1, and 26.8% type 2 DM. Patients with type 2 DM were older and had at admission higher creatinine, BUN, osmolality, sodium, and anion gap levels. Patients with new-onset of DM had higher levels of glucose and sodium, but lower potassium levels. No differences were found in pH or bicarbonate. Admission to the intensive care unit (ICU) was required in >50% of cases (p<0.001), and 86.6% of patients were finally admitted to a medical ward (p=0.005). The length of stay at the ICU (p<0.001) and hospital (p=0.013) was significantly different depending on DKA severity. CONCLUSIONS: Most DKA episodes require hospital admission, but mortality is <2%, and length of stay at the ER and medical ward depends on type of DM and initial severity of the episode.

Estado actual de los sistemas de infusión subcutánea continua de insulina y monitorización continua de glucosa en la Comunidad de Madrid / Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid

OBJETIVO: Analizar la información disponible sobre el estado de los sistemas de infusión subcutánea continua de insulina (ISCI) y de monitorización continua de glucosa (MCG) en la red pública sanitaria de la Comunidad Autónoma de Madrid (CAM). MATERIAL Y MÉTODOS: Se remitió una encuesta a los 28 servicios de endocrinología de los hospitales públicos de la CAM con 31 preguntas sobre los sistemas ISCI y MCG, que incluían registros de pacientes y aspectos asistenciales, administrativos y logísticos. Entre marzo y mayo de 2014 se recibieron respuestas de los centros y se recabó la información de los 20 servicios que realizaban este tipo de procedimientos en nuestra comunidad. Los datos sobre pacientes pediátricos se recibieron mayoritariamente a través de los servicios de adultos, con la excepción de 2 servicios de pediatría de los que la información se recibió directamente. RESULTADOS: En la CAM hay contabilizados un total de 1.256 sistemas ISCI en la población diabética. Los usuarios son mayoritariamente adultos (1.089 pacientes), mientras que 167 corresponden a pacientes pediátricos. Durante 2013 se instauraron 151 nuevos tratamientos (12% del total) mientras que se retiraron un total de 14 bombas. La disponibilidad de recursos asistenciales y la proporción de facultativos de plantilla encargados de estos tratamientos son muy desiguales entre distintos centros. Un 85% de los hospitales incluye entre sus prestaciones sistemas MCG retrospectivos, y un 40% los utiliza habitualmente al inicio de los tratamientos ISCI. Trece centros (65%) utilizan MCG a tiempo real (MCG-TR) a largo plazo en casos seleccionados, contabilizándose un registro acumulado de 67 pacientes. CONCLUSIONES: La implantación de las tecnologías en diabetes en la CAM es desigual en los distintos centros madrileños, y continúa siendo inferior a otros países de nuestro entorno, aunque parece observarse una discreta tendencia a recortar esas diferencias

OBJECTIVE: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. MATERIAL AND METHODS: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. RESULTS: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). CONCLUSIONS: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid]. / Estado actual de los sistemas de infusión subcutánea continua de insulina y monitorización continua de glucosa en la Comunidad de Madrid.

OBJECTIVE: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. MATERIAL AND METHODS: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. RESULTS: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). CONCLUSIONS: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use.

Resistencia insulínica, disfunción de la célula beta pancreática y diferencias en los puntos intermedios de las curvas de glucemia e insulina tras una sobrecarga oral estándar de glucosa en adultos con fibrosis quística / Insulin resistance, beta-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis

FUNDAMENTO: La diabetes se ha convertido en una comorbilidad prevalente que tiene un impacto negativo sobre el estado nutricional, la función pulmonar y la supervivencia en la fibrosis quística. OBJETIVO: Identificar alteraciones en los puntos intermedios del test de tolerancia oral a la glucosa de 2 h (OGTT), la disfunción de la célula β pancreática y la resistencia insulínica en la diabetes relacionada con la fibrosis quística. MÉTODOS: Analizamos de forma retrospectiva una serie de 64 pacientes mayores de 14 años, mediante los datos del primer OGTT patológico durante su seguimiento. Se determinaron la resistencia insulínica, usando el modelo HOMA-IR, la función de la célula β pancreática según Wareham, el tiempo en alcanzar la concentración máxima plasmática de insulina y glucosa y el área bajo la curva (AUC0-120). RESULTADOS: Se incluyeron 28 mujeres y 36 varones. La media de edad de la serie fue de 26,8 años. El 26,7% tenía una tolerancia normal (TGN), un 18,3% diabetes sin alteración de la glucosa en ayunas (CFRD sin FPG), el 10% una alteración indeterminada (INDET) y el 45% intolerancia hidrocarbonada (IGT). En los valores del HOMA-IR no se encontraron diferencias entre ningún grupo. Los casos con alguna alteración diagnóstica tenían una peor función de la célula β, con un retraso significativo en la secreción de insulina, aunque no hubo diferencias en su producción total (AUC0-120). El tiempo en alcanzar el pico máximo de glucosa era significativamente menor en los TGN frente al resto de categorías, siendo el AUC0-120 de glucosa mayor en las distintas categorías diagnósticas frente a TGN. CONCLUSIONES: En más de la mitad de los casos el pico máximo de glucemia en la OGTT se alcanza en puntos intermedios y no en el tiempo clásico de 120min. La secreción precoz de insulina está retrasada en los pacientes con fibrosis quística y alteraciones en el metabolismo de la glucosa, sin llegar a observarse diferencias en la producción total de la misma. La ausencia de alteraciones significativas en el HOMA-IR sugiere que la disfunción de la célula β es el principal mecanismo patogénico

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic mechanism

Diabetes en la fibrosis quística: una entidad diferente / Cystic fibrosis-related diabetes: a distinct condition

La fibrosis quística es la enfermedad genética letal con herencia autosómica recesiva más frecuente en la raza caucásica, afectando aproximadamente a uno por cada 2.000 nacidos vivos. La supervivencia de los pacientes con fibrosis quística ha mejorado gracias a los avances en los cuidados respiratorios y nutricionales, alcanzando un promedio de esperanza de vida comprendido entre los 30 y 40 años. La aparición de diabetes en la fibrosis quística es una comorbilidad que aumenta con la edad, con una prevalencia de hasta el 50% en los adultos. Su desarrollo se asocia a un empeoramiento de la función pulmonar y el estado nutricional, por lo que su diagnóstico precoz es esencial para mejorar la calidad de vida y clase funcional. El tratamiento con insulina de la diabetes y otras alteraciones precoces del metabolismo hidrocarbonado podría conllevar a una mejora de la función pulmonar y del estado nutricional de los pacientes con fibrosis quística

Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis

Cystic fibrosis-related diabetes: a distinct condition.

Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis.

Insulin resistance, ß-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic ß-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic ß-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse ß cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that ß-cell dysfunction is the main pathogenetic mechanism.

Dapagliflozina, el primer inhibidor SGLT 2 en el tratamiento de la diabetes tipo 2 / Dapagliflozin, the first SGLT-2 inhibitor in the treatment of type 2 diabetes

Dapagliflozina es el primer inhibidor selectivo del cotransportador de sodio-glucosa 2 (SGLT2) aprobado por la European Medicines Agency (Agencia Europea del Medicamento, EMA) para el tratamiento de la diabetes tipo 2. Dapagliflozina bloquea la reabsorción renal de glucosa, al inhibir el cotransportador SGLT2, produciendo un aumento de la excreción renal de glucosa y una reducción de los valores plasmáticos de glucosa. Su mecanismo de acción es independiente de la función de la célula β o de la modulación de la sensibilidad a la insulina. En los estudios fase III, dapagliflozina a dosis de 5 o 10 mg/día en monoterapia en pacientes no tratados previamente, o añadida a otros antidiabéticos como metformina, glimepirida, pioglitazona o insulina, reduce significativamente los valores de HbA1c y la glucemia en ayunas frente a placebo a las 24 semanas. Además, en el estudio comparativo frente a glipizida, dapagliflozina no fue inferior en el control de la glucosa a las 52 semanas cuando se utiliza como terapia añadida en pacientes diabéticos no controlados con metformina. En la mayoría de los ensayos clínicos dapagliflozina redujo el peso. La combinación de ambos efectos (mejoría del control glucémico y reducción ponderal) se alcanza en mayor grado en los tratamientos que combinan dapaglifozina. En los estudios de extensión, el efecto sobre el control glucémico y sobre la reducción ponderal se mantiene a los 2 y a los 4 años. Dapagliflozina fue bien tolerada. Las infecciones urinarias y genitales fueron más frecuentes en los pacientes que recibieron dapagliflozina que con placebo. Los episodios de hipoglucemia son escasos con dapagliflozina. En conclusión, dapagliflozina es una nueva opción terapéutica para el manejo de la diabetes tipo 2, sobre todo cuando se utiliza como terapia añadida a otros antidiabéticos (AU)

Dapagliflozin is the first novel sodium-glucose co-transporter-2 (SGLT2) inhibitor approved by the European Medicines Agency (EMA) for the treatment of type 2 diabetes. By inhibiting SGLT2, dapagliflozin blocks reabsorption of filtered glucose in the kidney, increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of pancreatic β cell function and modulation of insulin sensitivity. The results of phase III clinical trials showed that dapagliflozin, at a dose of 5 or 10 mg/day for 24 weeks as monotherapy in previously untreated patients, or as add-on combination therapy with metformin, glimepiride, pioglitazone or insulin-based therapy, significantly reduced both HbA1c and fasting plasma glucose levels compared with placebo. In addition, dapagliflozin was noninferior to glipizide, in terms of glycemic control after 52 weeks, when used as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. In most clinical trials, dapagliflozin reduced body weight. The combination of both effects (improved glycemic control and weight loss) is achieved to a greater extent in treatments that include dapaglifozin. Longer-term extension studies indicated that the efficacy of dapagliflozin on the glycemic control and weight reducción is maintained for up to 2 and 4 years. Dapagliflozin was well tolerated. Genital infections and urinary tract infections were more frequent in patients who received dapagliflozin than in placebo recipients. Hypoglycemic episodes were scarce with dapagliflozin. In conclusion, dapagliflozin is a novel option for the management of type 2 diabetes, particularly when used as add-on therapy (AU)

Perception of health and understanding of cardiovascular risk among patients with recently diagnosed diabetes and/or metabolic syndrome.

BACKGROUND: Cardiovascular (CV) disease mortality is increased in diabetes mellitus (DM) and metabolic syndrome (MS), conditions which share CV risk factors. AIM: The purpose of this study was to assess understanding of CV risk by patients with DM and/or MS diagnosed less than 1 year before and seen in primary care. Perception by these patients of their health state is also analysed. DESIGN: A multicentre, observational study in subjects diagnosed with DM diagnosed less than 1 year before and/or with MS, in whom agreement between CV risk perceived by patients and assessed by physicians was analysed. METHODS: Medical registry data and a survey of health status and perceived risk by patients and physicians. Agreement of patient perception of CV risk with perception of the physician in charge and with the CV risk established with clinical registry data was assessed. Self-perceived health status was also studied. RESULTS: A total of 150 physicians recruited 681 patients (71.5% with DM and 28.5% with MS) aged 60.8 ± 10.8 years (55.8% males). Good or excellent health were reported by 41.3% and 0.9%, respectively. Inability to give an estimate of CV risk was found in 39.8%. Agreement between the CV risks perceived by patients and evaluated by chart was poor: kappa index 0.145 (95% CI 0.101-0.189), p < 0.001. Agreement between CV risk perceived by patients and clinical data in the medical registry was weak: kappa index 0.165 (95% CI 0.117-0.213), p < 0.001. CONCLUSIONS: Patients with recently diagnosed DM and/or with MS have a poor awareness of their CV risk and 42.2% of them think that they have good or excellent health.

Partial central diabetes insipidus in patient with common variable immunodeficiency.

Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient's symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients.

Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes.

Our aim was to assess the ambulatory blood pressure monitoring (ABPM) characteristics or patterns in hypertensive patients with diabetes compared with non-diabetic hypertensives. We performed a cross-sectional analysis of a 68,045 patient database from the Spanish Society of Hypertension ABPM Registry, a nation-wide network of >1200 primary-care physicians performing ABPM under standardized conditions in daily practice. We identified 12,600 (18.5%) hypertensive patients with diabetes. When compared with patients without diabetes, diabetic hypertensives exhibited higher systolic blood pressure (BP) levels in every ABPM period (daytime 135.4 vs. 131.8, and nighttime 126.0 vs. 121.0 mm Hg, P<0.001 for both) despite they were receiving more antihypertensive drugs (mean number 1.71 vs. 1.23, P<0.001). Consequently, diabetic patients suffered from lack of control of BP more frequently than non-diabetic subjects particularly during the night (65.5% vs. 57.4%, P<0.001). Prevalence of a non-dipping BP profile (64.2% vs. 51.6%, P<0.001) was higher in diabetic patients. In the other hand, prevalence of 'white-coat' hypertension in diabetic patients was 33.0%. We conclude that there was a remarkably high prevalence of alterations in ABPM in patients with diabetes. Abnormalities in systolic BP, particularly during the night, and in circadian BP pattern could be linked with the excess of BP-related cardiovascular risk of diabetes. A wider use of ABPM in diabetic patients should be considered.