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Objetivo: La diabetes mellitus tipo 2 (DM2) y la osteoporosis son enfermedades asociadas con un entorno pro-inflamatorio, cuya prevención mediante nuevas estrategias terapéuticas podría evitar su desarrollo. Sin embargo, existe un escaso número de estudios que evalúen el perfil inflamatorio de la osteoporosis en pacientes con DM2. El objetivo de este estudio se centró en evaluar la respuesta inflamatoria inmunitaria mediante concentraciones séricas de nueve citocinas, dos de ellas de carácter anti-inflamatorio (IL-10, IL-5) y seis pro-inflamatorias (IL-2, IL-6, IL-12 (p70), IL-17A, TNFα e IFNɣ) en 163 individuos con DM2 y 47 controles. Una subpoblación, formada por 43 pacientes DM2 sin osteoporosis, y 33 con osteoporosis, fue analizada en más profundidad a nivel de parámetros óseos. Además, hemos evaluado las hormonas calciotropas, los marcadores de remodelado óseo, densidad mineral ósea y fracturas vertebrales en la población, y hemos analizado la relación de las citocinas ensayadas con la DM2, la osteoporosis y las fracturas vertebrales prevalentes. Los pacientes con DM2 tenían concentraciones séricas significativamente más altas de IL-10 en comparación con el grupo control (0,5±1 vs. 0,14±0,3 pg/ml; p=0,016) y los niveles de IL-12 p70 se mostraron más bajos en pacientes con DM2 respecto a los controles (2,9±1,6 vs. 3,9±3,1 pg/ml; p=0,027). En el grupo de pacientes con DM2 y osteoporosis, los niveles de la citocina IL-6 resultaron elevados respecto al grupo de DM2 sin osteoporosis (10,9±14,6 vs. 4,5±7,0; p=0,017). También se observó una asociación de IL-5, siendo sus niveles más bajos en el grupo DM2 con osteoporosis (1,7±0,2 vs. 3,8±0,6; p=0,032). Además, la IL-5 mostró una correlación directa con los niveles del biomarcador de formación ósea fosfatasa alcalina ósea (r=0,277, p=0,004) en la subpoblación de pacientes con DM2. El resto de citocinas no mostraron diferencias significativas. En conclusión, nuestros hallazgos demuestran que en nuestra población de estudio, los pacientes con DM2 respecto a sujetos sanos presentan un perfil inflamatorio opuesto a lo que se espera en situación de hiperglicemia, probablemente como respuesta compensatoria a la inflamación originada. El perfil de citocinas se modifica en la subpoblación de los pacientes diabéticos, dependiendo de la presencia de osteoporosis. En este caso, el perfil inflamatorio en presencia de osteoporosis es coherente con la respuesta esperada.

Introducción: La mayoría de estudios han puesto de manifiesto una disminución de la función y fuerza muscular en pacientes con diabetes mellitus tipo 2 (DM2). Sin embargo, la relación entre la función muscular y la salud ósea en los pacientes con DM2 no está bien definida. Objetivo: El objetivo del estudio fue analizar la relación entre la fuerza muscular y la fragilidad ósea en pacientes con DM2. Material y métodos: Estudio observacional transversal. Se incluyeron un total de 60 pacientes con DM2 (60% varones y 40% mujeres postmenopáusicas) con una edad entre 49-85 años. Se estudiaron variables demográficas, antropométricas, clínicas y bioquímicas. Se determinó la densidad mineral ósea (DMO) en columna lumbar (CL), cuello femoral y cadera total mediante DXA (Hologic QDR 4500), y los valores de TBS (TBS iNsight Software, versión 3.0.2.0, Medimaps, Merignac, France). La fuerza de la mano (kg/cm2) se midió con un dinamómetro hidráulico manual Jamar® (5030j1; jackson, MI). Para evaluar el nivel de movilidad y el riesgo de caídas, se realizó el test Time Up and Go. El análisis estadístico se realizó mediante el programa SPSS (SPSS, inc, v 25.0). Resultados: La edad media de los pacientes fue de 66,3±8,3 años. La HbA1c media fue de 7,7±1,1%, observándose un inadecuado control glucémico (HbA1c >7,5%) en el 73,3% de los pacientes. El 91,7% de las mujeres y el 77,8% de los varones presentaron baja fuerza muscular. El 41,7% de mujeres y el 25% de varones presentaron un riesgo elevado de caídas. Los sujetos con baja fuerza de prensión manual y los que tenían riesgo de caídas elevado presentaron valores significativamente menores de TBS que los que tenían mayor fuerza de la mano (0,99±0,17 vs 1,12±0,15; p=0,03) y bajo riesgo de caídas (0,94±0,13 vs 1,04±0,19; p=0,02). Los pacientes con TBS normal y parcialmente degradado tenían mayor fuerza de agarre manual que los sujetos con TBS degradado (p=0,031). La fuerza de la mano se asoció positivamente con TBS (p

Fundamento y objetivos: La diabetes mellitus tipo 2 (DM2) se asocia a un incremento del riesgo de fracturas cuyos mecanismos subyacentes son complejos. El objetivo de nuestro estudio fue analizar las variables que influyen en la concentración sérica de esclerostina y la relación con el metabolismo óseo en un grupo de pacientes DM2. Pacientes y métodos: Estudio transversal de 76 pacientes con DM2. Se recogieron datos clínicos, parámetros bioquímicos básicos, hormonas calciotropas, marcadores de remodelado óseo, radiología vertebral y densidad mineral ósea (DMO). Se determinaron las concentraciones séricas de esclerostina mediante ELISA (Biomedica, Austria). Resultados: Los varones presentaron concentraciones más elevadas que las mujeres (63,15±27,03 vs. 43,14±17,08 pmol/L, p

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

A common denominator of metabolic diseases, including type 2 diabetes Mellitus, dyslipidemia, and atherosclerosis, are elevated oxidative stress and chronic inflammation. These complex, multi-factorial diseases are caused by the detrimental interaction between the individual genetic background and multiple environmental stimuli. The cells, including the endothelial ones, acquire a preactivated phenotype and metabolic memory, exhibiting increased oxidative stress, inflammatory gene expression, endothelial vascular activation, and prothrombotic events, leading to vascular complications. There are different pathways involved in the pathogenesis of metabolic diseases, and increased knowledge suggests a role of the activation of the NF-kB pathway and NLRP3 inflammasome as key mediators of metabolic inflammation. Epigenetic-wide associated studies provide new insight into the role of microRNAs in the phenomenon of metabolic memory and the development consequences of vessel damage. In this review, we will focus on the microRNAs related to the control of anti-oxidative enzymes, as well as microRNAs related to the control of mitochondrial functions and inflammation. The objective is the search for new therapeutic targets to improve the functioning of mitochondria and reduce oxidative stress and inflammation, despite the acquired metabolic memory.

Aims: To examine the clinical and biochemical determinants of trabecular bone score (TBS) in type 2 diabetes mellitus (T2DM) patients., Methods: Cross-sectional observational study in 137 T2DM patients (49-85 years). Whole-body fat percentage was estimated using the relative fat mass (RFM) equation. Bone mineral density (BMD) and TBS were assessed using dual-energy X-ray absorptiometry and TBS iNsight Software respectively., Results: T2DM patients showed significantly lower TBS values (P < 0.001) despite significantly higher lumbar spine BMD (LS-BMD) (P = 0.025) compared to controls. TBS values ​​were negatively correlated with body mass index (BMI) (P < 0.001), waist circumference (P < 0.001), and HOMA-2IR index (P = 0.004) and positively correlated with sex hormone-binding globulin (SHBG) (P = 0.01) and LS-BMD (P = 0.003). RFM was negatively associated with TBS in both males (P < 0.001) and females (P = 0.005). The multivariate analysis showed that RFM, HOMA2-IR (negative), SHBG, and LS-BMD (positive) were the variables independently associated with TBS. ROC analysis revealed RFM as the variable with the highest predictive value for risk of degraded bone microarchitecture., Conclusions: The adiposity estimated by RFM may negatively affect TBS and this relationship may be influenced by insulin resistance and SHBG. RFM could act as a key estimator of degraded bone microarchitecture risk in the T2DM population., Competing Interests: Conflicts of interests None., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Osteoglycin (OGN) could be a biomarker of mild kidney function impairment in type 2 diabetes (T2D). Our study aimed to determine the association between serum OGN and impaired kidney function risk in T2D patients and to analyze its potential role as an estimator of kidney disturbances in this population. This cross-sectional study included 147 T2D patients (65 ± 8 years, 58.5% males), and 75 healthy controls (63 ± 10 years, 36% males). Circulating OGN levels were determined by ELISA. Linear regression modeling was performed to determine the variables influencing circulating OGN, and an ROC curve was plotted to assess the usefulness of OGN as an estimator of diabetic kidney disease risk. Circulating OGN was significantly increased in T2D patients compared to controls (18.41 (14.45-23.27) ng/mL vs. 8.74 (7.03-12.35) ng/mL; p < 0.001). We found a progressive increase in serum OGN according to the severity of kidney impairment in T2D patients (normal kidney function: 16.14 (12.13-20.48) ng/mL; mildly impaired kidney function: 19.15 (15.78-25.90) ng/mL; moderate impaired kidney function: 21.80 (15.06-29.22) ng/mL; p = 0.006). Circulating OGN was an independent estimator of mildly impaired kidney function risk in T2D patients. We suggest that serum OGN could act as an albuminuria-independent biomarker of incipient kidney dysfunction in T2D patients.

Background: Patients with primary hyperparathyroidism usually show decreased bone strength that are often not well diagnosed by conventional Dual-energy X-ray absorptiometry (DXA). Trabecular Bone Score (TBS) is a new technique for assessing bone microarchitecture indirectly. This cross-sectional study evaluates the usefulness of TBS in patients with primary hyperparathyroidism in clinical practice., Methodology: Bone mineral density (BMD) by DXA and TBS values by TBS InSight® software were determined in 72 patients with primary hyperparathyroidism to analyze its relationship with fragility fractures. A receiver operating curve was performed to evaluate the usefulness of TBS as predictor of fragility fractures. FRAX index with and without adjustment by TBS was calculated. Additionally, longitudinal data of a subgroup of patients according to the therapeutic management were also evaluated., Results: A total of 51.4% of the patients showed degraded microarchitecture while only 37.5% of them were diagnosed of osteoporosis by DXA. No significant correlation was found between TBS values and BMD parameters. However, TBS values were lower in osteoporotic patients compared to those classified as normal by BMD (1.16 ± 0.12vs 1.26 ± 0.17; p = 0.043) and in patients with fragility fractures compared to nonfractured patients (1.19 ± 0.03vs 1.24 ± 0.02, p < 0.001). The area under the curve for TBS performed better than the combination of femoral, hip and spine-BMD for prevalent fractures (0.714vs 0.679). TBS-adjusted FRAX was higher than nonadjusted model for both major osteoporotic and hip fracture (4.5% vs 3%; 0.9% vs 0.7%; p < 0.001). At follow-up, an improvement in TBS values was observed in treated patients (medical or surgical) vs nontreated close to significance (1.27 ± 0.10vs 1.24 ± 0.11, p = 0.074)., Conclusions: TBS could be a useful tool to identify increased fracture risk in patients with primary hyperparathyroidism underdiagnosed by BMD. Moreover, FRAX adjusted by TBS could be a more robust tool for predicting the risk of osteoporotic fracture to help in therapeutic decisions in this population., (Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

The retinoid X receptor-selective ligands has been used for advanced stages of cutaneous T-cell lymphoma refractory to previous systemic therapy, being bexarotene the first drug in this group approved in Europe. Multiple drug-related adverse events has been reported such as endocrine-metabolic disorders. We report 2 patients with cutaneous T-cell lymphoma, treated with bexarotene, that developed central hypothyroidism and dislipidaemia inmediately after the begining of this treatment. We also showed the successfully treatment response of these alterations and the total clinical remission after discontinuing the drug.