GH deficiency in patients with spinal cord injury : efficacy/safety of GH replacement, a pilot study

Growth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion. Nineteen consecutive patients with chronic thoracic complete SCI (AIS-A) were studied. Patients with low GH secretion were randomized in a double-blind, placebo-controlled study to receive either subcutaneous placebo injections or GH combined with physical therapy, for 6 months. Baseline cranial MRI, AIS motor and sensory scale, quality of life (spinal cord impact measurement) and modified Ashworth spasticity scale, quantitative sensory testing and neurophysiological exploration were assessed at baseline, 1, 3 and 6 months following treatment. Thirteen had GH deficiency. Seven received GH, five placebo and one dropped out. Both groups were similar according to clinical and demographical data at baseline, except for greater GH deficiency in the GH treatment group. At 6th month, patients treated with GH showed a significant improvement in SCIM-III score and in electrical perception threshold up to the 5th level below SCI, on both sides compared to baseline. GHD seems to be frequent in traumatic SCI and GH replacement is safe without side effects. GH combined with physical therapy can improve quality of life of SCI patients and, strikingly, the sensory perception below lesion level

GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study

Objective: Growth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion. Design and methods: Nineteen consecutive patients with chronic thoracic complete SCI (AIS-A) were studied. Patients with low GH secretion were randomized in a double-blind, placebo-controlled study to receive either subcutaneous placebo injections or GH combined with physical therapy, for 6 months. Baseline cranial MRI, AIS motor and sensory scale, quality of life (spinal cord impact measurement) and modified Ashworth spasticity scale, quantitative sensory testing and neurophysiological exploration were assessed at baseline, 1, 3 and 6 months following treatment. Results: Thirteen had GH deficiency. Seven received GH, five placebo and one dropped out. Both groups were similar according to clinical and demographical data at baseline, except for greater GH deficiency in the GH treatment group. At 6th month, patients treated with GH showed a significant improvement in SCIM-III score and in electrical perception threshold up to the 5th level below SCI, on both sides compared to baseline. Conclusions: GHD seems to be frequent in traumatic SCI and GH replacement is safe without side effects. GH combined with physical therapy can improve quality of life of SCI patients and, strikingly, the sensory perception below lesion level

Prefronto-cerebellar neuromodulation affects appetite in obesity

Human neuroimaging studies have consistently reported changes in cerebellar function and integrity in association with obesity. To date, however, the nature of this link has not been studied directly. Emerging evidence suggests a role for the cerebellum in higher cognitive functions through reciprocal connections with the prefrontal cortex. The purpose of this exploratory study was to examine appetite changes associated with noninvasive prefronto-cerebellar neuromodulation in obesity. 12 subjects with class I obesity (mean BMI 32.9 kg/m2) underwent a randomized, single-blinded, sham-controlled, crossover study, during which they received transcranial direct current stimulation (tDCS; active/sham) aimed at simultaneously enhancing the activity of the prefrontal cortex and decreasing the activity of the cerebellum. Changes in appetite (state and food-cue-triggered) and performance in a food-modified working memory task were evaluated. We found that active tDCS caused an increase in hunger and desire to eat following food-cue exposure. In line with these data, subjects also tended to make more errors during the working memory task. No changes in basic motor performance occurred. This study represents the first demonstration that prefronto-cerebellar neuromodulation can influence appetite in individuals with obesity. While preliminary, our findings support a potential role for prefronto-cerebellar pathways in the behavioral manifestations of obesity

Uso de lanreotida en combinación con cabergolina o pegvisomant en la práctica clínica en pacientes con acromegalia: el estudio ACROCOMB

[Abstract] PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.[Resumen] Propósito: Describir el uso de lanreotida en combinación terapéutica en acromegalia en la práctica clínica. Pacientes y métodos: ACROCOMB es un estudio observacional, retrospectivo, de pacientes con acromegalia activa tratados en centros hospitalarios españoles con lanreotida en combinación con cabergolina o pegvisomant entre 2006 y 2011. Se revisaron los datos clínicos de 108 pacientes tratados en 44 departamentos de endocrinología: 61 pacientes recibieron lanreótido/cabergolina (cohorte cabergolina) y 47 lanreotida/pegvisomant (cohorte pegvisomant). Resultados: La edad mediana de los pacientes fue de 50,8 años en la cohorte de cabergolina y 42,7 años en la de pegvisomant. Los tratamientos médicos previos a la combinación con lanreótido fueron análogos de somatostatina (SSA) en monoterapia (40 [66%] pacientes) o agonistas de la dopamina (7 [11%] pacientes) en la cohorte de cabergolina y SSA (29 [62%] pacientes) y pegvisomant en monoterapia (16 [34%] pacientes) en la de pegvisomant. Doce pacientes no habían recibido tratamiento previo y en 4 pacientes se desconocía la terapia previa. La mediana de duración del tratamiento fue de 1,6 años (0,1-6) y 2,1 años (rango 0,4 a 6,3) en las cohortes de cabergolina y pegvisomant, respectivamente. Al inicio del estudio el valor mediano del factor de crecimiento de insulina-I era 149% el límite superior normal (LSN) (15-505%) en la cohorte de cabergolina y 156% LSN (15-534%) en la de pegvisomant. Al final del estudio se redujeron a 104% LSN (13-557%) p < 0,001 y 86% LSN (23-345%) p < 0,0001, respectivamente. Al final del estudio, se reportaron valores normales de factor de crecimiento de insulina-I ajustados por edad en el 48% de los pacientes tratados con lanreotida/cabergolina y 70% de los tratados con lanreotida/pegvisomant. No hubo cambios significativos en los parámetros hepáticos, cardíacos o glucémicos. Conclusión: En la práctica clínica las combinaciones con lanreotida son una opción útil en el tratamiento de pacientes con acromegalia que no está bien controlada en monoterapia, ya sea con SSA carbegolina o pegvisomant; particularmente, la combinación de lanreotida y pegvisomant tiene una alta eficacia y se tolera bien

Growth hormone as concomitant treatment in severe fibromyalgia associated with low IGF-1 serum levels. A pilot study

<p>Abstract</p> <p>Background</p> <p>There is evidence of functional growth hormone (GH) deficiency, expressed by means of low insulin-like growth factor 1 (IGF-1) serum levels, in a subset of fibromyalgia patients. The efficacy of GH versus placebo has been previously suggested in this population. We investigated the efficacy and safety of low dose GH as an adjunct to standard therapy in the treatment of severe, prolonged and well-treated fibromyalgia patients with low IGF-1 levels.</p> <p>Methods</p> <p>Twenty-four patients were enrolled in a randomized, open-label, best available care-controlled study. Patients were randomly assigned to receive either 0.0125 mg/kg/d of GH subcutaneously (titrated depending on IGF-1) added to standard therapy or standard therapy alone during one year. The number of tender points, the Fibromyalgia Impact Questionnaire (FIQ) and the EuroQol 5D (EQ-5D), including a Quality of Life visual analogic scale (EQ-VAS) were assessed at different time-points.</p> <p>Results</p> <p>At the end of the study, the GH group showed a 60% reduction in the mean number of tender points (pairs) compared to the control group (p < 0.05; 3.25 ± 0.8 <it>vs</it>. 8.25 ± 0.9). Similar improvements were observed in FIQ score (p < 0.05) and EQ-VAS scale (p < 0.001). There was a prompt response to GH administration, with most patients showing improvement within the first months in most of the outcomes. The concomitant administration of GH and standard therapy was well tolerated, and no patients discontinued the study due to adverse events.</p> <p>Conclusion</p> <p>The present findings indicate the advantage of adding a daily GH dose to the standard therapy in a subset of severe fibromyalgia patients with low IGF-1 serum levels.</p> <p>Trial Registration</p> <p>NCT00497562 (ClinicalTrials.gov).</p

Assessment of obesity stigma and discrimination among Spanish subjects with a wide weight range : the OBESTIGMA study

This study aims to assess the extent of rejection and instances of stigmatization linked to obesity within the Spanish population, encompassing a diverse spectrum of weights ranging from normal weight to morbid obesity. Additionally, the study seeks to identify the primary factors influencing these experiences and further examines the impact of bariatric surgery on such dynamics. Multicenter observational study with involving a total of 1,018 participants who were recruited from various Obesity Units. Negatives attitudes towards people with obesity were assessed through three questionnaires: (i) Antifat Attitudes Scale (AFA), (ii) Stigmatizing Situations Inventory (SSI) and (iii) Weight Bias Internalization Scale (WBIS). Subjects were categorized into four groups based on their BMI and history of prior bariatric surgery. The cumulative score across all questionnaires (AFA, SSI and WBIS) exhibited a progressive increase, from participants with normal weight to those with obesity (p < 0.001 for all). Within the AFA questionnaire, males showed more rejection towards people with obesity than women, also perceiving obesity as a disease linked to a lack of willpower (p = 0.004 and p = 0.030, respectively). The overall SSI score was negatively associated with age (r = −0.080, p = 0.011), with young participants encountering more stigmatizing experiences than their adult counterparts. Neither employment status nor educational demonstrated a significant association with any of the questionnaires. Interestingly, patients who underwent lost weight following bariatric surgery did not exhibit improved outcomes. Individuals with obesity demonstrate a heightened level of aversion towards the disease compared to those with normal weight. Concurrently, the incidence of stigmatizing encounters displays a concerning escalation among younger individuals

Assessment of obesity stigma and discrimination among Spanish subjects with a wide weight range: the OBESTIGMA study

IntroductionThis study aims to assess the extent of rejection and instances of stigmatization linked to obesity within the Spanish population, encompassing a diverse spectrum of weights ranging from normal weight to morbid obesity. Additionally, the study seeks to identify the primary factors influencing these experiences and further examines the impact of bariatric surgery on such dynamics.Materials and methodsMulticenter observational study with involving a total of 1,018 participants who were recruited from various Obesity Units. Negatives attitudes towards people with obesity were assessed through three questionnaires: (i) Antifat Attitudes Scale (AFA), (ii) Stigmatizing Situations Inventory (SSI) and (iii) Weight Bias Internalization Scale (WBIS). Subjects were categorized into four groups based on their BMI and history of prior bariatric surgery.ResultsThe cumulative score across all questionnaires (AFA, SSI and WBIS) exhibited a progressive increase, from participants with normal weight to those with obesity (p &lt; 0.001 for all). Within the AFA questionnaire, males showed more rejection towards people with obesity than women, also perceiving obesity as a disease linked to a lack of willpower (p = 0.004 and p = 0.030, respectively). The overall SSI score was negatively associated with age (r = −0.080, p = 0.011), with young participants encountering more stigmatizing experiences than their adult counterparts. Neither employment status nor educational demonstrated a significant association with any of the questionnaires. Interestingly, patients who underwent lost weight following bariatric surgery did not exhibit improved outcomes.ConclusionIndividuals with obesity demonstrate a heightened level of aversion towards the disease compared to those with normal weight. Concurrently, the incidence of stigmatizing encounters displays a concerning escalation among younger individuals

Characteristics of patients with type 2 diabetes mellitus newly treated with GLP-1 receptor agonists (CHADIG Study): a cross-sectional multicentre study in Spain

Objective: Several glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1Ra) have been made recently available in Spain for type 2 diabetes mellitus (DM2) treatment. There are no published data on the clinical and sociodemographic profile of patients initiating treatment with GLP-1Ra in Spain. Our objective was to understand these patients' characteristics in a real-world clinical practice setting. Design: Cross-sectional observational study. Setting: Spanish specialist outpatient clinics. Participants: 403 adults with DM2 initiating GLP-1Ra treatment were included. Primary and secondary outcome measures: Sociodemographic and DM2-related clinical data, including treatment at and after GLP-1Ra initiation and comorbidities, were collected. Results: Evaluable patients (n=403; 50.9% female) were included ( July 2013 to March 2014) at 24 centres by 53 specialists (47 endocrinology, 6 internal medicine), with the following profile (value±SD): age (58.3±10.4 years), diabetes duration (9.9±7 years), body mass index (BMI; 36.2±5.5) and glycated haemoglobin (HbA1c; 8.4±1.4%); 14% had HbA1c≤7%. Previous antidiabetic treatment: 53.8% only oral antidiabetic drugs (OADs), 5.2% insulin and 40% insulin and OAD; of those receiving OAD, 35% single drug, 38.2% 2 drugs and 24% 3 drugs. Concomitant to GLP-1Ra, 55.3% were only on OAD, 36.2% on insulin and OAD, and 7.2% only on insulin. Of those receiving OAD, the GLP-1Ra was mainly associated with 1 drug (65%) or 2 drugs (31.8%). GLP-1Ra are frequently added to existing antidiabetic drugs, with dipeptidyl peptidase-4 inhibitors being the OAD most frequently switched (45% receiving 1 before starting GLP-1Ra, only 2.7% receiving it concomitantly). Conclusions: In Spain, GLP-1Ra therapy is usually started in combination with OADs or OADs and insulin. These drugs are used in relatively young patients often not reaching therapeutic goals with other treatment combinations, roughly a decade after diagnosis and with a relatively high BMI. The latter could be explaine

Bariatric surgery: evidence-based practical recommendations

[Resumen] La obesidad mórbida es, habitualmente, refractaria a los tratamientos convencionales, por lo que la modificación de hábitos dietéticos y de actividad física y/o el uso de fármacos consiguen pérdidas de peso parciales con habitual recuperación posterior. La cirugía bariátrica constituye una opción terapéutica para los casos de obesidad con elevado índice de masa corporal (IMC) asociada a comorbilidades, con buenos resultados a corto y largo plazo. El Grupo de Trabajo sobre Obesidad de la Sociedad Española de Endocrinología y Nutrición (GOSEEN) ha elaborado un documento con recomendaciones prácticas basadas en la evidencia para el tratamiento quirúrgico de la obesidad. La revisión se estructura en 3 partes. En la primera se definen los conceptos de obesidad y comorbilidades asociadas, los tratamientos médicos y sus resultados, las indicaciones y contraindicaciones para el tratamiento quirúrgico con los criterios de selección de los pacientes, el manejo pre y perioperatorio y la valoración de grupos especiales, como adolescentes y personas de edad avanzada. En la segunda parte se describen las distintas técnicas quirúrgicas, las vías de acceso y los resultados comparativos, las complicaciones tanto a corto como a largo plazo, la repercusión de la pérdida ponderal sobre las comorbilidades y los criterios para evaluar la efectividad de la cirugía. En la tercera parte se desarrolla el seguimiento postoperatorio, el control dietético en fases tempranas y más tardías tras la cirugía, y el calendario de control médico y analítico con la suplementación de los distintos macro y micronutrientes en función de la técnica quirúrgica empleada. Se incluye un apartado final sobre gestación y cirugía bariátrica, así como tablas y gráficos complementarios al texto desarrollado. La cirugía bariátrica sigue siendo un tratamiento discutido para la obesidad, pero los resultados en la corrección del exceso ponderal con mejoría en las patologías asociadas y en la calidad de vida confirman que puede ser el tratamiento de elección en pacientes seleccionados, con la técnica quirúrgica apropiada y con un correcto control pre y postoperatorio.[Abstract] Morbid obesity is usually refractory to conventional treatments. Consequently, weight that is lost by modifying diet and exercise and/or the use of drugs is usually later regained. Bariatric surgery constitutes a therapeutic option in obese patients with a high body mass index associated with comorbidities and achieves good results in both the short and the long term. The Obesity Working Group of the Spanish Society of Endocrinology and Nutrition has produced a document with practical, evidencebased recommendations for the surgical treatment of obesity. The review is structured in three parts. The first part defines the concepts of obesity and associated comorbidities, medical treatments, their results, and the indications and contraindications for surgical treatment, as well as the criteria for patient selection, pre- and perisurgical management, and assessment of special groups such as adolescents and the elderly. The second part discusses the different surgical techniques, approaches and comparative results, short- and long-term complications, the repercussions of weight loss on comorbidities, and the criteria for assessing the effectiveness of surgery. The third part discusses postsurgical follow-up, dietary control in the early and subsequent stages after surgery and the schedule for medical and laboratory follow-up, together with the different macro- and micronutrient supplements that should be used depending on the surgical technique employed. A final section is included on pregnancy and bariatric surgery, as well as tables and figures that complement the text. Although bariatric surgery continues to be a questionable treatment for obesity, the results correcting excess weight, with improvements in associated comorbidities and in quality of life, confirm that this option could be the treatment of choice in selected patients when the appropriate surgical technique and correct preand postoperative follow-up are employed

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline