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Aims To determine the first manifestation of cardiovascular or kidney disease (CVKD) and associated resource use in type 2 diabetes mellitus (T2DM) patients during seven years of follow-up. Methods Observational-retrospective secondary data study using medical records of patients aged ≥18 years with T2DM and without prior CVKD between 2013 and 2019. The index date was 01/01/2013 (fixed date). The manifestation of CVKD was defined by the first diagnosis of heart-failure (HF), chronic-kidney disease (CKD), myocardial-infarction (MI), stroke or peripheral-artery disease (PAD). The main variables were baseline characteristics, manifestation of CVKD, mortality, resource use and costs. Descriptive analyses and Cox model were applied to the data. Results 26,542 patients were selected (mean age: 66.6 years, women: 47.8%, mean duration of T2DM: 17.1 years). 18.7% (N = 4974) developed a first CVKD manifestation during the seven years [distribution: HF (22.4%), CKD (36.6%), MI (14.5%), stroke (15.3%) and PAD (11.3%)]. Overall mortality was 8.3% (N = 2214). The mortality risk of the group that developed HF or CKD as the first manifestation compared to the CVKD-free cohort was higher [HR: 2.5 (95% CI: 1.8–3.4) and 1.8 (95% CI: 1.4–2.3)], respectively. The cumulative costs per patient of HF (€50,942.80) and CKD (€48,979.20) were higher than MI (€47,343.20) and stroke (€47,070.30) and similar to PAD (€51,240.00) vs. €13,098.90 in patients who did not develop CVKD, p Conclusions In T2DM patients, HF and CKD were the first most common manifestations and had higher mortality and re-hospitalisation rates. HF and CKD were associated with the highest resource use and costs for the Spanish National-Health-System.

Heart failure (HF) and chronic kidney disease (CKD) are the most frequent first cardiorenal conditions in patients with type 2 diabetes (T2D), which can be exacerbated by other comorbidities, such as hypertension, dyslipidemia, and obesity. To improve their clinical outcomes, patients with T2D need to achieve and maintain glycemic targets, as well as prevent cardiorenal disease onset and progression. Several clinical trials evaluating the sodium-glucose cotransporter type 2 inhibitors (SGLT2i) dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin have shown consistent risk reduction in major adverse cardiovascular events and/or hospitalization for HF, together with lower risk of kidney disease progression. The benefits associated with SGLT2i in T2D are distinct from other antihyperglycemic drugs since they have been proposed to exert pleiotropic metabolic and direct effects on the kidney and the heart. In this review, we summarize and discuss the evidence regarding the mechanisms of action, the efficacy and safety profiles, and the clinical guidelines on the use of the therapeutic class of SGLT2i, highlighting their role in cardiorenal prevention beyond glycemic control.

Objectives To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) Results In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin–angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064–1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387–1.493)] and UACR progression [HR 1.323 (95% CI 1.182–1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment.

Uno de los principios configuradores de la sociedad cooperativa es el conocido principio de “puerta abierta”, conforme al cual el socio cooperativista puedecausar baja en la misma cuando lo desee, si bien ajustándose a los requisitos al efecto previstos en las normas legales y estatutarias. La presente sentencia trata el tema del plazo dentro del cual la cooperativa ha de pagar el importe del reembolso al socio que ha causado baja voluntaria en la misma. Cuando el momento de ese pago se condiciona a la entrada de un nuevo socio que sustituya al que causó baja, si tal condición no se cumple dentro del plazo máximo establecido por la Ley, el pago ha de efectuarse en todo caso dentro de este plazo.

Background: \ud Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries.\ud \ud Methods: \ud Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code.\ud \ud Findings: \ud The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries.\ud \ud Interpretation: \ud We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed.\ud \ud Funding: \ud The study was sponsored by AstraZeneca.

Objectives: To describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial). Methods: Observational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) 30 mg/g. Results: We identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8 mg/g, eGFR 49.7 mL/min/1.73 m2). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population. Conclusions: In Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit. Resumen: Objetivos: Describir la epidemiología, el perfil clínico, los tratamientos y los eventos cardiovasculares y renales, tras 2 años de seguimiento en una población contemporánea con enfermedad renal crónica (ERC) en España. También se analizó en la población tipo DAPA-CKD (pacientes que cumplían la mayoría de criterios del estudio DAPA-CKD). Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La población con ERC se definió como pacientes ≥ 18 años, con al menos un código diagnóstico de ERC antes de la fecha índice (01/01/2018). La ERC se definió como filtrado glomerular estimado (FGe) 30 mg/g. Resultados: Se identificaron 56.435 pacientes con ERC, tras exclusiones (76,4 años, 52,2% varones, cociente albúmina-creatinina 390,8 mg/g, FGe 49,7 ml/min/1,73 m2). La prevalencia fue del 4,91% y la incidencia 2,10/1.000 pacientes/año. El 69,2% tomaba inhibidores del sistema renina-angiotensina (solo el 4,2% a dosis máximas) y el 3,5% de los diabéticos inhibidores SGLT-2. Tras 2 años, las tasas de insuficiencia cardiaca, muerte, infarto de miocardio, ictus y ERC fueron 17,9; 12,1; 7,2; 6,3; 5,9 eventos/100 pacientes/año, respectivamente. Además, el 44% hospitalizaron y el 6,8% murieron durante la hospitalización. Los eventos cardiovasculares fueron más frecuentes en la población tipo DAPA-CKD. Conclusiones: En España, la población con ERC es mayor, y las comorbilidades, incluyendo diabetes e insuficiencia cardiaca, comunes. Los eventos cardiovasculares y renales son frecuentes. Hay margen de mejora en el manejo de la ERC, especialmente a través del empleo de fármacos con beneficio cardiovascular y renal.

Background Data about the impact of chronic kidney disease (CKD) on health care costs in Spain are scarce This study was aimed to evaluate cumulative costs and healthcare utilisation in CKD in Spain. Methods Observational, retrospective, population-based study, which included adults who received care for CKD between 2015 and 2019. Healthcare and medication costs were summarized on a yearly basis starting from the index date (1st January 2015), and then cumulatively until 2019. Results We identified 44,214 patients with CKD (year 2015: age 76.4 ± 14.3 years, 49.0% women, albumin-to-creatinine ratio 362.9 ± 176.8 mg/g, estimated glomerular filtration rate 48.7 ± 13.2 mL/min/1.73 m2). During the 2015–2019 period, cumulative CKD associated costs reached 14,728.4 Euros, being cardiovascular disease hospitalizations, particularly due to heart failure and CKD, responsible for 77.1% of costs. Total medication cost accounted for 6.6% of the total cost. There was a progressive decrease in cardiovascular disease hospital costs per year (from 2741.1 Euros in 2015 to 1.971.7 Euros in 2019). This also occurred with cardiovascular and diabetic medication costs, as well as with the proportion of hospitalizations and mortality. Costs and healthcare resources use were higher in the DAPA-CKD like population, but also decreased over time. Conclusions Between 2015 and 2019, costs of patients with CKD in Spain were high, with cardiovascular hospitalizations as the key determinant. Medication costs were responsible for only a small proportion of total CKD costs. Improving CKD management, particularly with the use of cardiovascular and renal protective medications may be helpful to reduce CKD burden.

Objective Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. Methods The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists. Objetivo El tratamiento de la diabetes tipo 2 (DM2) es complejo y su propósito es reducir la morbimortalidad, por lo que su manejo tiene que incluir: un control glucémico individualizado precoz (mediante una adecuada educación diabetológica, modificaciones del estilo de vida y tratamiento farmacológico), el control de los factores de riesgo cardiovascular (CV), la detección y tratamiento precoz de las complicaciones y la evaluación de las comorbilidades asociadas. El objetivo fue elaborar un documento para unificar los aspectos necesarios para el abordaje integral de las personas con DM2. Participantes Miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Métodos Se realizó una revisión de la evidencia disponible relativa a cada aspecto del manejo de la diabetes: objetivos de control glucémico, dieta y ejercicio, tratamiento farmacológico, tratamiento y control de factores de riesgo, detección de complicaciones y manejo del paciente frágil con DM2. Las recomendaciones se formularon según los grados de evidencia recogidos en los Standards of Medical Care in Diabetes 2018. Tras la formulación de las recomendaciones el documento fue consensuado por los miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Conclusiones El objetivo de este documento es proporcionar, desde el punto de vista del endocrinólogo clínico, unas recomendaciones prácticas basadas en la evidencia acerca de todos los aspectos necesarios para el abordaje integral de la DM2. Sin financiación 1.180 JCR (2019) Q4, 133/143 Endocrinology & Metabolism No data SJR 2019 No data IDR 2019 UEM

Objetivo El tratamiento de la diabetes tipo 2 (DM2) es complejo y su propósito es reducir la morbimortalidad, por lo que su manejo tiene que incluir: un control glucémico individualizado precoz (mediante una adecuada educación diabetológica, modificaciones del estilo de vida y tratamiento farmacológico), el control de los factores de riesgo cardiovascular (CV), la detección y tratamiento precoz de las complicaciones y la evaluación de las comorbilidades asociadas. El objetivo fue elaborar un documento para unificar los aspectos necesarios para el abordaje integral de las personas con DM2. Participantes Miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Métodos Se realizó una revisión de la evidencia disponible relativa a cada aspecto del manejo de la diabetes: objetivos de control glucémico, dieta y ejercicio, tratamiento farmacológico, tratamiento y control de factores de riesgo, detección de complicaciones y manejo del paciente frágil con DM2. Las recomendaciones se formularon según los grados de evidencia recogidos en los Standards of Medical Care in Diabetes 2018. Tras la formulación de las recomendaciones el documento fue consensuado por los miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Conclusiones El objetivo de este documento es proporcionar, desde el punto de vista del endocrinólogo clínico, unas recomendaciones prácticas basadas en la evidencia acerca de todos los aspectos necesarios para el abordaje integral de la DM2. Objective Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. Methods The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists. Sin financiación No data JCR 2019 0.312 SJR (2019) Q3, 178/245 Endocrinology, Diabetes and Metabolism No data IDR 2019 UEM

Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM.Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology.The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members.This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.

The levels of neurotrophins and their receptor mRNAs were measured in rat sciatic nerve, after 6 or 12 weeks of streptozotocin-induced diabetes. Expression of neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) was decreased by 50 and 29%, respectively, compared with age-matched controls after 12 weeks of diabetes. Expression of brain-derived neurotrophic factor (BDNF) was not detected. In addition, diabetes induced a reduction in the expression levels of the neurotrophin receptors; trk B mRNA decreased by 50% after 6 weeks of diabetes, but returned to control levels after 12 weeks; meanwhile the trk C and the p75 LNGFR transcripts were reduced by 20% of control at both times studied. trk A expression was below detection limits. Thus, these data suggest that a reduction in neurotrophin and neurotrophin receptors could contribute to the development and maintenance of diabetic neuropathy.

A 48-year-old male patient had arrest due to rupture of a dissecting aneurysm of the thoracic aorta into the pericardial cavity with tamponade; he received treatment in a general hospital lacking the facilities to practice heart surgery. The patient was treated by means of intermittent pericardial drainage while being transferred to another hospital at 100-km distance for surgical treatment.