Search

This work comprehensively investigates the systematic integration of highly relevant life events and physiological parameters with continuous glucose monitoring (CGM) data to understand the synergy in glucoregulatory systems. Multitask learning (MTL) is employed in learning from numerous subjects while tailoring features in patient-specific layers. Systematic combinations of inputs are fed to the system providing personalized blood glucose level (BGL) predictions at multi-step prediction horizons (PHs) as output. Three cutting-edge long-short-term memory (LSTM) networks are adapted in the shared layers of MTL architecture. Moreover, PHs are varied with 30-minute intervals up to 120 minutes to identify the long-term effects of relevant input features on BGL prediction suggesting optimal deep learning (DL) architecture. The empirical result demonstrates that the most relevant features for BGL prediction are glucose, bolus insulin, and carbohydrate estimate from meals, while exercise and basal insulin rate have momentary effects. The best predictive root means square error (RMSE) achieved are $16.06~\pm ~2.74$ , $30.89~\pm ~4.31$ , $40.51~\pm ~5.16$ , and $47.31~\pm ~5.78$ mg/dL for 30-, 60-, 90-, and 120-min PH, respectively, while maintaining $94.06~\pm ~3.08$ % predictions in clinically safe zones (A + B) at 120-min PH in Clarke error grid analysis (EGA). The insights learned from the experiments will assist in selecting appropriate DL models, features, and timelines based on specific needs, with significant promise in improving T1D management through better therapeutic and lifestyle modification.

Abstract Objective Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy. Methods Sixteen-week-old male Zucker Obese rats (ZO; n = 64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg−1•day−1; ZOSV); Group 3: valsartan (31 mg•kg−1•day−1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg−1•day−1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage. Results Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val decreased aortic stiffness and reversed impairment in nitric oxide-induced vascular relaxation in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective than val in ameliorating DD. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, cytokine array revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val, suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val, but not val, increased IL-4, which is increasingly recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity-associated DD. Conclusions These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.

During exercise, there is coordination between various hormonal systems to ensure glucoregulation. This study examined if hypoglycemia occurs during moderate-intensity exercise in non-obese and obese individuals with and without type 2 diabetes (T2D). Eighteen non-obese, 18 obese, and 10 obese with T2D completed 2 study days that included a meal at 1,800 h followed by rest (NOEX) or exercise (PMEX; 45 min/55% of VO2 max 2 h post meal). Glucose, insulin, and glucagon concentrations were measured throughout this 5.5 h period. Subjects with T2D had elevated glucose responses to the meal on both study days, compared to non-obese and obese subjects (P < 0.05). During evening exercise (PMEX), subjects with T2D had a greater drop in glucose concentration (−98.4 ± 13.3 mg/dL) compared to obese (−44.8 ± 7.1 mg/dL) and non-obese (−39.3 ± 6.1 mg/dL; P < 0.01) subjects. Glucose levels decreased more so in females than males in both conditions (P < 0.01). Nadir glucose levels

La obesidad es una de las enfermedades más antiguas del mundo, sin embargo hasta hace relativamente poco se ha reconocido como tal, debido a su gran incidencia en la salud pública por sus características epidémicas y por las funestas asociaciones que la acompañan. Aún cuando es sus comienzos esta acumulación de energía permitió la supervivencia en épocas de hambruna, la evolución hormonal que implica este fenómeno la ha convertido en una afección epidémica, propiciada por el sedentarismo y la sobre alimentación. El sueño de nuestros ancestros de comida disponible con menor esfuerzo ha llegado a ser una pesadilla. Un gran número de factores hormonales producidos en diversos tejidos por más de 450 genes se encargan de mantener una homeostasis energética cuya alteración puede promover la obesidad; a su vez los adipocitos hipertróficos producen adipocinas que alteran el metabolismo de la glucosa, predisponiendo a diabetes mellitus y a la lesión del endotelio vascular generando enfermedad cardiovascular. La obesidad se constituye así en un estado proinflamatorio crónico de bajo grado. Las diferentes estrategias de tratamiento de esta enfermedad multifactorial implican una disminución en el aporte y un aumento del gasto energéticos. El tratamiento definitivo a muy largo plazo posiblemente resulte del desarrollo de la biología molecular, sin embargo en el momento actual ese horizonte está tan lejano que el conocimiento de las graves complicaciones de la obesidad, los esfuerzos educativos, los cambios en el medio ambiente y en el estilo de vida son críticos para enfrentar el desafío.

El hipotiroidismo subclínico y sus consecuencias clínicas ha sido objeto de debate científico por espacio de varias décadas. A raíz de la publicación de la declaración de consenso acerca de la disfunción tiroidea subclínica en el año 2005, realizada por la Sociedad Americana de Endocrinologìa (The Endocrine Society), la Asociación Americana de Endocrinólogos Clínicos (AACE) y la Asociación Americana de la Tiroides (ATA) se abrió un nuevo espacio para los endocrinólogos en el manejo de algunas disfunciones tiroideas que no habían sido tenidas en cuenta dentro del campo de accion terapéutico. Los autores hacen un recuento de cómo se produce el cambio en los paradigmas y en el enfoque diagnostico y terapéutico. Luego hacen un recuento de algunas de las experiencias desarrolladas en Colombia. Finalmente sugieren algunos derroteros a partir de su propia experiencia y también basados en logros científicos de otras fuentes obtenidos en otros campos de la Endocrinologìa moderna.

La neoplasia endocrina multiple tipo 2 comprende tres sindromes : la neoplasia endocrina múltiple 2A con predisposición genética para desarrollar carcinoma medular del tiroides, feocromocitoma e hiperplasia primaria de paratiroides. La neoplasia endocrina múltiple 2B, desorden autosómico dominante con feocromocitoma y carcinoma medular del tiroides que generalmente se presenta a una edad más temprana y es más agresivo que la de tipo 2A, por lo que su diagnóstico precoz es crítico; estos pacientes, que también presentan neuromas mucosos, ganglioneuromas intestinales y hábito marfanoide, no desarrollan hiperparatiroidismo. Y el carcinoma medular familiar del tiroides, sin ninguna otra manifestación clínica de neoplasia endocrina múltiple 2A o 2B. Se han identificado mutaciones activadoras del proto-oncogene RET en todas las variantes de la neoplasia endocrina múltiple tipo 2. Las mutaciones del RET en la neoplasia endocrina múltiple 2B ocurren principalmente (95%) en las regiones que codifican para el dominio de tirosina cinasa, en los codones 883 y 918. No obstante las múltiples modalidades de tratamiento para los cánceres tiroideos, especialmente para el carcinoma medular, la sobrevida de los pacientes afectados no ha mejorado. Por tanto el desarrollo de nuevas estrategias de tratamiento, incluída la terapia génica, parece esperanzador para estos pacientes. La clonación de los cotrasportadores sodio-yoduro, ha abierto una nueva puerta para la terapia génica citorreductiva basada en la transferencia genética de los cotrasportadores, seguida por la ablación con yodo radiactivo (131I). Presentamos un caso esporádico de neoplasia endocrina múltiple 2B en una niña asociado a una mutación en el codón 918 del exón 16 del proto-oncogene RET.

We studied the presence of antithyroid antibodies in subjects with slight to overt thyroid disfunction. Fifty nine subjects that showed goiter or TSH levels above 5.0 mU/L were included. The percentage of patients with positive anti Thyroid Peroxidase antibodies (anti TPO) was 18.63%. From them, 90.9% exhibited goiter along with thyroid dysfunction, whereas only 9.1 % had goiter without thyroid disfunction. There was no patient without goiter that showed anti TPO levels above 100 mUl/ mL.We conclude that thyroid autoimmune disease is very prevalent among our patients, so it must be suspected in subjects with or without goiter, as well as in those with slight thyroid disfunction, because it could progress to overt hypothyroidism.

Tuberculosis y embarazo: una experiencia institucional. Autor: Luz Amparo Díaz Cruz. Tutora: Dra. María Teresa Peralta Abello, Profesora Asociada del Departamento de Ginecología. / Artritis séptica en el paciente pediátrico Autores: Fabio M. Ramírez, Patricia Uricoechea y Carlos Vásquez. Tutores: Drs. Mauricio Palau, Infectólogo, Pediatra, Profesor Asociado; Edgar Rojas, Pediátra, Profesor Asociado; Eduardo Alvarez, Jefe del Servicio de Infectología, Hospital Pediátrico de La Misericordia. / Resistencia a la insulina. Autor: Dr. Guido Lastra. Profesor Asociado del Departamento de Medicina Interna. Unidad de Endocrinología. / Riesgo de pérdida visual postoperatoria en glaucoma avanzado. Autor: Dr. John Jairo Martínez Cardona. Tutor: Dr. Gabriel Ortiz Arizmendi, Instructor Asociado, Departamento de Cirugía, Facultad de Medicina. Universidad Nacional de Colombia.

La Prolactina (HPr) constituye, junto con la Hormona de Crecimiento (GH) y el Lactógeno placentario (HPL) el conjunto hormonal de las Somatomamotrofinas. El parentesco estructural y especial de estas tres hormonas polipeptídicas, fabricadas dos de ellas (HPr y GH) en las cédulas lactotrofas y somatotrofas hipofisiarias y la otra por la placenta (HPL) permiten suponer la existencia de una hormona ancestral común debido al gran porcentaje de identidad de sus residuos de aminoácidos, hecho que a la vez explica la superposición de acciones por ellas desarrolladas; aun cuando cada una de ellas posee su acción fundamental y característica.

La endocrinopatía múltiple Tipo I se caracteriza por la presencia simultánea de tumores, o hiperplasias, en hipófisis, paratiroides y páncreas, originando el cuadro clínico de hiperfunción endocrina múltiple. En el presente informe se presenta el caso de una paciente joven quien consultó por síntomas compatibles con hipoglicemia y cuyo estudio demostró la presencia concomitante de hipoglicemia con hiperinsulinemia, hiperprolactinemia y secreción excesiva de hormona de crecimiento con respuesta parad6jica a la hiperglicemia y al estímulo con TRH; clínicamente mostraba signos de acromegalia. Este cuadro lo producía un tumor de células beta (insulinoma) y un tumor mixto hipofisiario (prolactinoma, somatotrofinoma). La paciente fue intervenida quirúrgicamente con éxito en cuanto al apudoma pancreático y el tumor hipofisiario fue tratado médicamente con bromocriptina, con remisión total de su sintomatología. A propósito de este caso se discuten los conceptos actuales sobre las lesiones neuroendocrinas múltiples.

Gestational diabetes mellitus (GDM) is a condition where diabetes is diagnosed during pregnancy. Women with GDM have an increased risk of adverse pregnancy outcomes and a higher likelihood of developing type 2 diabetes and cardiovascular disease (CVD) later in life. The mechanisms behind this increased risk are not well understood, but obesity and endothelial dysfunction have been identified as potential factors. A recent study found that women with a history of GDM exhibited impaired vascular insulin sensitivity, endothelial dysfunction, and increased oxidative stress. These findings suggest that interventions to reverse early cardiovascular abnormalities in women with GDM may help reduce their long-term risk of CVD. Further research is needed to explore the role of vascular insulin sensitivity in different racial and ethnic groups. [Extracted from the article]

Diabetes mellitus confers a high risk of cardiovascular morbidity and mortality and requires aggressive management of all cardiovascular risk factors, including diabetic dyslipidemia. Although levels of low-density lipoprotein cholesterol are often normal or only slightly elevated in persons with diabetes, lipid-altering therapy with statins has been shown in large, randomized, controlled trials to decrease the risk of cardiovascular complications in this patient population. A target low-density lipoprotein cholesterol level of <70 mg/dL is now a therapeutic option in patients at very high risk for coronary heart disease, including patients with diabetes. Diabetes is also a leading cause of end-stage renal disease. In addition to their lipid-modifying effects, statins have been shown to slow the progression of diabetic nephropathy and potentially exert other renoprotective effects; these benefits, however, remain to be confirmed in clinical trials.