Effectiveness of Combined First-Line Medical Treatment in Acromegaly with Prolactin Co-secretion.

OBJECTIVE: To compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin co-secreting PA (GH&PRL-PA). DESIGN: Retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least six months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analysed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs. 51.9 ± 12.7 years; p < 0.01) and harboring more frequently macroadenomas (89.7% vs. 72.1%, p = 0.03). First generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs. 15.2%; p < 0.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs. 55.1%, p = 0.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first line medical treatment in combination with fgSRLs in these subgroups of patients.

Pegvisomant or pasirotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

AIM: 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) and compare to those caused by a GH-Pit-NET. METHODS: A multicenter retrospective study of patients with acromegaly on treatment with pasireotide 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. RESULTS: 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 neither 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). CONCLUSION: 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 is observed between both groups, and both drugs are effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study.

BACKGROUND/OBJECTIVES: Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. SUBJECTS/METHODS: A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. RESULTS: A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. CONCLUSION: Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.

Cognitive Functioning and Cortical Brain Thickness in Acromegaly Patients: A Pilot study.

OBJECTIVE: Cognitive effects in acromegaly patients are poorly understood and the mechanisms involved are still unclear. The aim of this study was to evaluate the cognitive function, depression, and quality of life of acromegaly patients treated with pegvisomant versus somatostatin analogues (SRLs) and to analyze the effect of the different treatments on cognition and possible structural brain changes. METHODS: This cross-sectional study involved 23 acromegaly patients divided into two groups according to treatment modality: One group of 9 patients treated with pegvisomant and another group of 14 patients treated with SRLs. All participants underwent blood analysis, neuropsychological tests, depression tests, quality of life assessment, and 3-Tesla magnetic resonance imaging. RESULTS: We found no significant differences between groups in the neuropsychological tests, depression or quality of life; nor in the whole-brain cortical thickness. In the SRL group, the volume of the thalamus correlated positively with executive function, a correlation not found in the pegvisomant group. In addition, the pegvisomant group had significantly higher levels of insulin than the SRL group. CONCLUSIONS: In conclusion, in this pilot study, the type of pharmacological treatment in patients with acromegaly and good glycemic control did not influence the cognitive function and cortical brain thickness. However, pegvisomant could play a neuroprotective role on the thalamus that will have to be demonstrated with larger samples in future studies.

Randomized Study to Evaluate the Impact of Telemedicine Care in Patients With Type 1 Diabetes With Multiple Doses of Insulin and Suboptimal HbA1c in Andalusia (Spain): PLATEDIAN Study.

OBJECTIVE: To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients' health-related quality of life (HRQoL), and physicians' satisfaction in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: PLATEDIAN (Telemedicine on Metabolic Control in Type 1 Diabetes Mellitus Andalusian Patients) (NCT03332472) was a multicenter, randomized, 6-month follow-up, open-label, parallel-group controlled study performed in patients with type 1 diabetes with suboptimal metabolic control (HbA1c <8% [<64 mmol/mol]), treated with multiple daily injections. A total of 388 patients were assessed for eligibility; 379 of them were randomized 1:1 to three face-to-face visits (control cohort [CC]) (n = 167) or the replacement of an intermediate face-to-face visit by a telemedicine visit using Diabetic (intervention cohort [IC]) (n = 163). The primary efficacy end point was the mean change of HbA1c levels from baseline to month 6. Other efficacy and safety end points were mean blood glucose, glucose variability, episodes of hypoglycemia and hyperglycemia, patient-reported outcomes, and physicians' satisfaction. RESULTS: At month 6, the mean change in HbA1c levels was -0.04 ± 0.5% (-0.5 ± 5.8 mmol/mol) in the CC and 0.01 ± 0.6% (0.1 ± 6.0 mmol/mol) in the IC (P = 0.4941). The number of patients who achieved HbA1c <7% (<53 mmol/mol) was 73 and 78 in the CC and IC, respectively. Significant differences were not found regarding safety end points at 6 months. Changes in HRQoL between the first visit and final visit did not differ between cohorts, and, regarding fear of hypoglycemia (FH-15 score ≥28), statistically significant differences observed at baseline remained unchanged at 6 months (P < 0.05). CONCLUSIONS: The use of telemedicine in patients with type 1 diabetes with HbA1c <8% (<64 mmol/mol) provides similar efficacy and safety outcomes as face-to-face visits.

Exposición solar en la enfermedad inflamatoria intestinal ambulatoria: factores predictivos y correlación con la concentración sérica de vitamina D / Sunlight exposure in inflammatory bowel disease outpatients: Predictive factors and correlation with serum vitamin D

Introducción: La exposición solar es el principal determinante del estado de vitaminaD. Nuestro objetivo fue describir las prácticas de exposición y protección solar de una serie de pacientes con enfermedad inflamatoria intestinal (EII) y evaluar su influencia en la concentración sérica de vitaminaD. Pacientes y métodos: Estudio observacional de tipo transversal. Las variables clínico-demográficas se obtuvieron mediante entrevista clínica y revisión de la historia. La evaluación de la exposición solar se realizó mediante el Sun Exposure Questionnaire. La concentración de 25-hidroxivitaminaD (25OHD) se determinó por electroquimioluminiscencia. Se realizaron cuestionarios de calidad de vida, actividad física, ingesta semanal de vitaminaD y hábitos de protección solar. Resultados: Se incluyeron 149 pacientes. En el 69% de los pacientes se registraron valores deficientes o insuficientes de 25OHD. El 67% presentaron una baja exposición solar. Se observó una modesta correlación significativa entre la puntuación total del cuestionario de exposición solar y la concentración de 25OHD en la serie completa (r=0,226; p=0,006) y en verano (r=0,274; p=0,01). La puntuación del cuestionario de protección solar no influyó en la concentración de 25OHD. En el análisis multivariado solo la presencia de actividad clínica se asoció a una exposición solar baja (OR=3,23). Discusión: La exposición solar de acuerdo con el cuestionario empleado fue baja, se asoció a la presencia de actividad clínica y se correlacionó débilmente con la concentración de 25OHD sérica. Se necesitan más estudios que exploren el uso de cuestionarios individuales de exposición solar y su correlación con la vitaminaD sérica en la EII

Introduction: Sunlight exposure is the main source of vitaminD. Our aim was to describe both sun exposure and sun protection behaviour in a series of patients with inflammatory bowel disease (IBD), and to study their potential association with vitaminD concentration. Patients and methods: A cross sectional, observational study. The clinical-demographic variables were obtained via clinical interviews and medical history review. The sunlight exposure assessment was carried out using the Sun Exposure Questionnaire and the concentration of 25-hydroxy vitaminD (25OHD) was measured by an electro-chemiluminescence immunoassay. Questionnaires were conducted on quality of life, physical activity, weekly vitaminD intake and sun protection behaviour. Results: 149 patients were included. In 69% of patients, deficient or insufficient 25OHD values were recorded. 67% showed low sun exposure. A modest significant correlation was observed between the total score of the solar exposure questionnaire and the 25OHD concentration in the complete series (r=0.226, P=.006) and in the summer (r=0.274, P=.01). The sun protection behaviour questionnaire score did not influence the 25OHD concentration. In the multivariate analysis, only the presence of clinical activity was associated with low sun exposure (OR=3.23). Discussion: Sun exposure according to the questionnaire used was low, was associated with the presence of clinical activity and was weakly correlated with serum 25OHD concentration. More studies are needed to explore the use of individual questionnaires for sun exposure and its relationship with vitaminD in patients with IBD

Sunlight exposure in inflammatory bowel disease outpatients: Predictive factors and correlation with serum vitaminD. / Exposición solar en la enfermedad inflamatoria intestinal ambulatoria: factores predictivos y correlación con la concentración sérica de vitamina D.

INTRODUCTION: Sunlight exposure is the main source of vitaminD. Our aim was to describe both sun exposure and sun protection behaviour in a series of patients with inflammatory bowel disease (IBD), and to study their potential association with vitaminD concentration. PATIENTS AND METHODS: A cross sectional, observational study. The clinical-demographic variables were obtained via clinical interviews and medical history review. The sunlight exposure assessment was carried out using the Sun Exposure Questionnaire and the concentration of 25-hydroxy vitaminD (25OHD) was measured by an electro-chemiluminescence immunoassay. Questionnaires were conducted on quality of life, physical activity, weekly vitaminD intake and sun protection behaviour. RESULTS: 149 patients were included. In 69% of patients, deficient or insufficient 25OHD values were recorded. 67% showed low sun exposure. A modest significant correlation was observed between the total score of the solar exposure questionnaire and the 25OHD concentration in the complete series (r=0.226, P=.006) and in the summer (r=0.274, P=.01). The sun protection behaviour questionnaire score did not influence the 25OHD concentration. In the multivariate analysis, only the presence of clinical activity was associated with low sun exposure (OR=3.23). DISCUSSION: Sun exposure according to the questionnaire used was low, was associated with the presence of clinical activity and was weakly correlated with serum 25OHD concentration. More studies are needed to explore the use of individual questionnaires for sun exposure and its relationship with vitaminD in patients with IBD.

Vitamin D in Inflammatory Bowel Disease: Biological, Clinical and Therapeutic Aspects.

BACKGROUND: Vitamin D has an immunoregulatory action in Inflammatory Bowel Disease (IBD) as well as other immune-mediated disorders. Its influence on intestinal permeability, innate and adaptive immunity, and the composition and diversity of the microbiota contribute to the maintenance of intestinal homeostasis. Patients with IBD have a greater prevalence of vitamin D deficiency than the general population, and a possible association between this deficit and a worse course of the disease. However, intervention studies in patients with IBD have proved inconclusive. OBJECTIVE: To review all the evidence concerning the role of vitamin D as an important factor in the pathophysiology of IBD, review the associations found between its deficiency and the prognosis of the disease, and draw conclusions for the practical application from the main intervention studies undertaken. METHODS: Structured search and review of basic, epidemiological, clinical and intervention studies evaluating the influence of vitamin D in IBD, following the basic principles of scientific data. RESULTS: Vitamin D deficiency is associated with disease activity, quality of life, the consumption of social and healthcare resources, and the durability of anti-TNFα biological treatment. Determination of new metabolites of vitamin D, measurement of its absorption capacity and questionnaires about sun exposure could help identify groups of IBD patients with a special risk of vitamin D deficiency. CONCLUSION: Well-designed intervention studies are needed in IBD, with probably higher objective plasma doses of vitamin D to establish its efficacy as a therapeutic agent with immunomodulatory properties. Meanwhile, vitamin D deficiency should be screened for and corrected in affected patients in order to achieve adequate bone and phosphocalcic metabolism.

Deficiencia de vitamina D en pacientes ambulatorios con enfermedad inflamatoria intestinal: prevalencia y asociación con la actividad clínica-biológica / Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence and association with clinical-biological activity

Introducción: los datos sobre la prevalencia del déficit de vitamina D en pacientes con enfermedad inflamatoria intestinal (EII) en España son escasos. Dicha deficiencia podría asociarse a un peor curso evolutivo. Objetivo: determinar la prevalencia de deficiencia de 25-hidroxivitamina D (25OHD) en una cohorte de pacientes ambulatorios con enfermedad inflamatoria intestinal y evaluar su asociación con la actividad clínica-biológica, la calidad de vida y síntomas psicológicos. Material y métodos: estudio observacional unicéntrico de tipo transversal. Las variables de estudio se obtuvieron mediante entrevista clínica, revisión del historial médico y cuestionarios validados (escala de ansiedad y depresión hospitalaria y cuestionario corto de calidad de vida de la EII). La determinación de 25OHD fue hecha en el mismo laboratorio por inmunoanálisis de electroquimioluminiscencia. Resultados: se analizaron 224 pacientes. La prevalencia de deficiencia de vitamina D en enfermedad de Crohn (EC) y colitis ulcerosa (CU) fue de un 33,3% y un 20,3% respectivamente. En EC, la deficiencia de vitamina D se asoció con una mayor actividad clínica (p < 0,001) y una mayor concentración de calprotectina fecal (p = 0,01). En CU, hubo asociación con la actividad clínica (p < 0,001), el uso de esteroides en el último semestre (p = 0,001) y los ingresos hospitalarios en el año previo (p = 0,003). En un subanálisis de 149 pacientes no se observó asociación de vitamina D con la calidad de vida ni con las subpuntuaciones de la escala de ansiedad y depresión hospitalaria. Conclusiones: la deficiencia de vitamina D es frecuente en pacientes con enfermedad inflamatoria intestinal. Se observó una asociación entre su concentración y los índices clínicos de actividad, así como con los niveles de calprotectina fecal en enfermedad de Crohn

Introduction: there are few data on the prevalence of vitamin D deficiency in patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be associated with a worse course of the disease. Aim: to determine the prevalence of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and assess its association with clinical and biological activity, quality of life and psychological symptoms. Methods: a cross-sectional, single-center observational study was performed. The study variables were obtained via clinical interviews, medical chart review and validated questionnaires (Hospital Anxiety and Depression Scale and Short Quality of Life in Inflammatory Bowel Disease Questionnaire). 25OHD was measured in the same laboratory by an electro-chemiluminescence immunoassay. Results: the study included 224 patients. The prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was 33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was associated with a higher clinical activity (p < 0.001) and a higher concentration of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with clinical activity (p < 0.001), the use of steroids during the last six months (p = 0.001) and hospital admission during the previous year (p = 0.003). A sub-analysis of 149 patients failed to detect an association between vitamin D and quality of life or the scores of the Hospital Anxiety and Depression Scale. Conclusions: vitamin D deficiency is common in patients with inflammatory bowel disease. An association was found between vitamin D concentration and clinical activity indexes, as well as fecal calprotectin levels in Crohn's disease

Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence and association with clinical-biological activity.

INTRODUCTION: there are few data on the prevalence of vitamin D deficiency in patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be associated with a worse course of the disease. AIM: to determine the prevalence of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and assess its association with clinical and biological activity, quality of life and psychological symptoms. METHODS: a cross-sectional, single-center observational study was performed. The study variables were obtained via clinical interviews, medical chart review and validated questionnaires (Hospital Anxiety and Depression Scale and Short Quality of Life in Inflammatory Bowel Disease Questionnaire). 25OHD was measured in the same laboratory by an electro-chemiluminescence immunoassay. RESULTS: the study included 224 patients. The prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was 33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was associated with a higher clinical activity (p < 0.001) and a higher concentration of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with clinical activity (p < 0.001), the use of steroids during the last six months (p = 0.001) and hospital admission during the previous year (p = 0.003). A sub-analysis of 149 patients failed to detect an association between vitamin D and quality of life or the scores of the Hospital Anxiety and Depression Scale. CONCLUSIONS: vitamin D deficiency is common in patients with inflammatory bowel disease. An association was found between vitamin D concentration and clinical activity indexes, as well as fecal calprotectin levels in Crohn's disease.

Actualización de probióticos, prebióticos y simbióticos en nutrición clínica / An update on probiotics, prebiotics and symbiotics in clinical nutrition

Se revisa el concepto de prebióticos, probióticos y simbióticos y su empleo en diferentes situaciones de la práctica clínica diaria relacionados con la nutrición clínica. Se analiza su papel en el tratamiento y/o prevención de la diarrea (aguda, por antibióticos, rádica), en la enfermedad inflamatoria intestinal (colitis ulcerosa y reservoritis), sobre la salud colónica (estreñimiento, intestino irritable), hepatopatías (esteatosis y encefalopatía mínima), en pacientes de cuidados intensivos, quirúrgicos y sometidos a trasplante hepático. Si bien parece demostrada su eficacia en la prevención de la diarrea por antibióticos y en la reservoritis en la colitis ulcerosa, son necesarios más estudios para poder establecer recomendaciones en la mayoría de escenarios clínicos. El riesgo de infección asociado al uso de probióticos es relativamente bajo; no obstante, existen grupos seleccionados de pacientes en los que se recomienda emplearos con cautela (como la infusión a nivel yeyunal) (AU)

The concept of prebiotics, probiotics, and symbiotics and their use in different situations of daily clinical practice related to clinical nutrition is reviewed, as well as their role in the treatment/prevention of diarrhea (acute, induced by antibiotics, secondary to radiotherapy), inflammatory bowel disease (ulcerative colitis and pouchitis), in colonic health (constipation, irritable bowel), in liver disease (steatosis and minimum encephalopathy), and in intensive care, surgical, and liver transplantation. While their effectiveness for preventing antibiotic-induced diarrhea and pouchitis in ulcerative colitis appears to be shown, additional studies are needed to establish recommendations in most clinical settings. The risk of infection associated to use of probiotics is relatively low; however, there are selected groups of patients in whom they should be used with caution (as jejunum infusion) (AU)

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca2+ signaling ([Ca2+]i), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca2+]i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca2+]i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response.

An update on probiotics, prebiotics and symbiotics in clinical nutrition. / Actualización de probióticos, prebióticos y simbióticos en nutrición clínica.

The concept of prebiotics, probiotics, and symbiotics and their use in different situations of daily clinical practice related to clinical nutrition is reviewed, as well as their role in the treatment/prevention of diarrhea (acute, induced by antibiotics, secondary to radiotherapy), inflammatory bowel disease (ulcerative colitis and pouchitis), in colonic health (constipation, irritable bowel), in liver disease (steatosis and minimum encephalopathy), and in intensive care, surgical, and liver transplantation. While their effectiveness for preventing antibiotic-induced diarrhea and pouchitis in ulcerative colitis appears to be shown, additional studies are needed to establish recommendations in most clinical settings. The risk of infection associated to use of probiotics is relatively low; however, there are selected groups of patients in whom they should be used with caution (as jejunum infusion).

Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study / Comparación entre múltiples dosis de insulina (insulina glargina una vez al día y lispro en las comidas) e infusión subcutánea continua de insulina con monitorización continua de glucosa en pacientes con diabetes tipo 1 metabólicamente optimizados. Estudio randomizado

Background and objective: Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL). Methods: A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6 ± 1.8% (70.5 ± 15.4 mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data. Results: After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72 ± 18.38 vs. 92.07 ± 17.65; p < 0.028), a 0.5% decrease in HbA1c values (8.4 ± 1.2 vs. 7.9 ± 0.7% [68 ± 9.7 vs. 63 ± 5.5 mmol/mol]; p < 0.032), an improvement in glycaemic variability (standard deviation 66.9 ± 14 vs. 59.4 ± 16 mg/dl; p < 0.05), a decrease in insulin requirements (0.87 ± 0.29 vs. 0.80 ± 0.25 U/kg; p < 0.049), a decrease in number of severe hypoglycaemia episodes (0.44 ± 0.9 vs. 0.05 ± 0.2; p < 0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8 ± 10.9% vs. 23 ± 18.4%; p < 0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9 ± 0.7 vs. 7 ± 0.6% [63 ± 5.5 vs. 53 ± 4.5 mmol/mol]; p < 0.001) and EsQOL (91.66 ± 22 vs. 84.53 ± 1.63; p < 0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7 ± 0.6% [53 ± 4.5 mmol/mol] vs. MDI/G 7.6 ± 0.9% 59.6 ± 7.7 mmol/mol];p < 0.03). Conclusions: Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes (AU)

Introducción y objetivo: Las ventajas de la infusión subcutánea continua de insulina (ISCI) sobre múltiples inyecciones diarias de insulina con glargina (MDI/G) son todavía inciertas. Comparamos ISCI frente a MDI/G en pacientes con diabetes tipo 1 sin indicación de terapia ISCI utilizando la monitorización continua de glucosa (CGSM). Los objetivos primarios fueron el control glucémico y la calidad de vida (QOL). Métodos: Un total de 45 pacientes con diabetes 1 de largo tiempo de evolución y valores medios de HbA1c de 8,6 ± 1,8% (70,5 ± 15,4 mmol/mol), previamente tratados con MDI/NPH, fueron cambiados a MDI/G durante 6 meses y luego sin cumplir criterios clínicos para terapia ISCI asignados aleatoriamente a ISCI o MDI/G durante seis meses. Se evaluó la calidad de vida (EsDqol) y el control de la glucemia mediante la medición de los niveles de HbA1c, la tasa de hipoglucemias, cetoacidosis y datos de CGSM. Resultados: Después de la primera fase (MDI/NPH a MDI/G) hubo una mejora significativa en EsDQOL total (99,72 ± 18,38 vs. 92,07 ± 17,65; p < 0.028), una disminución de 0,5% en los valores de HbA1c (8,4 ± 1,2 vs. 7,9 ± 0,7% [68 ± 9,7 vs. 63 ± 5,5 mmol/mol]; p < 0,032), una mejora en la variabilidad de la glucemia (desviación estándar 66,9 ± 14 vs. 59,4 ± 16 mg/dl; p <0,05), una disminución en las necesidades de insulina (0,87 ± 0,29 vs. 0,80 ± 0,25 U/kg; p <0,049), una disminución en el número de episodios de hipoglucemia grave (0,44 ± 0,9 vs. 0,05 ± 0,2; p <0,014), y un aumento en los periodos de normoglucemia medidos con CGSM (15,8 ± 10,9% vs. 23 ± 18,4%; p <0,003). Seis meses después de la aleatorización, se observaron mejoras significativas en la HbA1c (7,9 ± 0,7 vs. 7 ± 0,6%; [63 ± 5,5 vs. 53 ± 4.5 mmol/mol]; p <0,001) y la calidad de vida (91,66 ± 22 vs. 84,53 ± 1,63; p <0,045) sólo en el grupo ISCI. El valour de HbA1c fue significativamente menor en ISCI en comparación con el grupo MDI/G (CSII 7 ± 0,6% [53 ± 4,5 mmol/mol] vs. MDI/G 7,6 ± 0,9% [59,6 ± 7,7 mmol/mol]; p < 0,03). Conclusiones: La terapia insulínica intensiva con ISCI vs. MDI/G se asoció con mejores niveles de HbA1c en pacientes con diabetes tipo 1 de larga evolución (AU)

Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study.

BACKGROUND AND OBJECTIVE: Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL). METHODS: A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data. RESULTS: After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03). CONCLUSIONS: Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes.

[TOTAL PARENTERAL NUTRITION IN A PREGNANT PATIENT WITH ACUTE PANCREATITIS AND LIPOPROTEIN LIPASE DEFICIENCY]. / NUTRICIÓN PARENTERAL TOTAL EN UNA PACIENTE GESTANTE CON PANCREATITIS AGUDA E HIPERTRIGLICERIDEMIA POR DÉFICIT DE LIPOPROTEÍN LIPASA.

We present a case of severe acute pancreatitis induced by hypertriglyceridemia secondary to lipoprotein lipase (LPL) deficiency in a pregnant patient with gestational diabetes, initially maneged with diet but it was later necessary to carry out artificial nutricional support measures: total parenteral nutrition. LPL deficiency might cause severe hypertriglyceridemia, repetition acute pancreatitis which is an unwieldy and severe situation during pregnancy. Acute familial hypertriglyceridemia pancreatitis accounts for 5% of cases, including LPL deficiency. The goal of treatment is to reach triglycerides levels below 500 mg/dl, being very low fat diet the treatment of choice, drugs or plasmapheresis techniques can also be associated. TPN enriched in ω3 fatty acids and glutamine was safe and effective in our patient with significant decrease in triglyceride levels.

Presentamos un caso de pancreatitis aguda severa inducida por hipertrigliceridemia secundaria a déficit de lipoproteín lipasa (LPL) en una paciente gestante con diabetes gestacional, manejada inicialmente con dieta, siendo necesario posteriormente llevar a cabo medidas de soporte nutricional artificial: nutrición parenteral total. El déficit de LPL causa hipertrigliceridemia severa y, frecuentemente, pancreatitis aguda de repetición, situación de difícil manejo y de importante gravedad durante la gestación. La pancreatitis aguda por hipertrigliceridemia familiar supone el 5% de los casos, incluyéndose el déficit de LPL. El objetivo del tratamiento será alcanzar niveles de triglicéridos inferiores a 500 mg/dl, siendo la dieta muy baja en grasa el tratamiento de elección, pudiéndose asociar también fármacos o técnicas de plasmaféresis. La nutrición parenteral total enriquecida en ácidos grasos 3 y glutamina resultó segura y eficaz en la paciente, con un descenso importante de los niveles de triglicéridos.

Nutrición parenteral total en una paciente gestante con pancreatitis aguda e hipertrigliceridemia por déficit de lipoproteín lipasa / Total parenteral nutrition in a pregnant patient with acute pancreatitis and lipoprotein lipase deficiency

Presentamos un caso de pancreatitis aguda severa inducida por hipertrigliceridemia secundaria a déficit de lipoproteín lipasa (LPL) en una paciente gestante con diabetes gestacional, manejada inicialmente con dieta, siendo necesario posteriormente llevar a cabo medidas de soporte nutricional artificial: nutrición parenteral total. El déficit de LPL causa hipertrigliceridemia severa y, frecuentemente, pancreatitis aguda de repetición, situación de difícil manejo y de importante gravedad durante la gestación. La pancreatitis aguda por hipertrigliceridemia familiar supone el 5% de los casos, incluyéndose el déficit de LPL. El objetivo del tratamiento será alcanzar niveles de triglicéridos inferiores a 500 mg/dl, siendo la dieta muy baja en grasa el tratamiento de elección, pudiéndose asociar también fármacos o técnicas de plasmaféresis. La nutrición parenteral total enriquecida en ácidos grasos w3 y glutamina resultó segura y eficaz en la paciente, con un descenso importante de los niveles de triglicéridos (AU)

We present a case of severe acute pancreatitis induced by hypertriglyceridemia secondary to lipoprotein lipase (LPL) deficiency in a pregnant patient with gestational diabetes, initially maneged with diet but it was later necessary to carry out artificial nutricional support measures: total parenteral nutrition. LPL deficiency might cause severe hypertriglyceridemia, repetition acute pancreatitis which is an unwieldy and severe situation during pregnancy. Acute familial hypertriglyceridemia pancreatitis accounts for 5% of cases, including LPL deficiency. The goal of treatment is to reach triglycerides levels below 500 mg/dl, being very low fat diet the treatment of choice, drugs or plasmapheresis techniques can also be associated. TPN enriched in w3 fatty acids and glutamine was safe and effective in our patient with significant decrease in triglyceride levels (AU)

Relación entre déficit de vitamina D y síndrome metabólico / Relationship between vitamin D deficiency and metabolic syndrome

Fundamento y objetivo: El déficit de vitamina D y el síndrome metabólico son 2 entidades muy frecuentes en población española. Se ha sugerido que los pacientes con síndrome metabólico pueden tener déficit de vitamina D con mayor frecuencia que los sujetos sin e'l, y que unos valores bajos de vitamina D pueden predisponer al desarrollo de síndrome metabólico. No obstante, los resultados de estudios prospectivos y de intervención han sido diversos, sin que se haya aclarado por el momento si existe esta relación. El objetivo de este trabajo fue evaluar la relación entre los valores de 25-hidroxivitamina D y la prevalencia e incidencia del síndrome metabólico. Pacientes y método: Se realizó un estudio poblacional de cohortes. Al inicio del estudio (1996-1998), 1.226 pacientes fueron evaluados. Las visitas de seguimiento se llevaron a cabo en 2002-2004 y 2005-2007. Basalmente y durante el seguimiento, los participantes se sometieron a una entrevista y un examen clínico estandarizado con una prueba de tolerancia oral a la glucosa. En la segunda visita se midieron la 25-hidroxivitamina D y los valores de parathormona intacta. Resultados: La prevalencia de síndrome metabólico en la segunda y la tercera evaluación fue del 29,4 y del 42,5%, respectivamente. Los valores medios (DE) de 25-hidroxivitamina D fueron menores en los pacientes con síndrome metabólico, 21,7 (6,21) frente a 23,35 (6,29) ng/ml, p < 0,001. La prevalencia de deficiencia de vitamina D (25-hidroxivitamina D < 20 ng/ml) en la segunda evaluación fue del 34,7%, con diferencias significativas entre los sujetos con y sin síndrome metabólico (34,6 frente a 26,5%, p < 0,01). Los varones con deficiencia de vitamina D tuvieron con mayor frecuencia hipertensión y síndrome metabólico que aquellos con valores normales. Las mujeres con deficiencia de vitamina D tuvieron más frecuentemente hiperglucemia, hipertensión, aumento de la circunferencia de la cintura e hipertrigliceridemia. En el estudio prospectivo, los valores de 25-hidroxivitamina D < 20 ng/ml no se asociaron significativamente con un mayor riesgo de desarrollar el síndrome metabólico en los siguientes 5 años (odds ratio 0,99, intervalo de confianza del 95% 0,57-1,7, p < 0,97) después de ajustar por sexo y edad. Conclusiones: Los pacientes con síndrome metabólico tienen con mayor frecuencia déficit de vitamina D, pero este no predice el riesgo de desarrollar síndrome metabólico (AU)

Background and objective: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. Patients and methods: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. Results: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P < .001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D < 20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P < .01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitaminD values < 20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P = .97) after adjusting by sex and age. Conclusions: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome (AU)

[Relationship between vitamin D deficiency and metabolic syndrome]. / Relación entre déficit de vitamina D y síndrome metabólico.

BACKGROUND AND OBJECTIVE: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. PATIENTS AND METHODS: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. RESULTS: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age. CONCLUSIONS: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome.