A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.

Dynamic fronto-amygdalar interactions underlying emotion-regulation deficits in women at higher weight.

OBJECTIVE: The regulation of negative emotions entails the modulation of subcortical regions, such as the amygdala, by prefrontal regions. There is preliminary evidence suggesting that individuals at higher weight may present with hypoactivity in prefrontal regulatory systems during emotional regulation, although the directionality of these pathways has not been tested. In this study, we compared fronto-amygdalar effective connectivity during cognitive reappraisal as a function of BMI in 48 adult women with obesity and 54 control participants. METHODS: Dynamic causal modeling and parametric empirical Bayes were used to map effective connectivity between the dorsomedial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and the amygdala. RESULTS: Difficulty in Emotion Regulation Scale scores were higher in the obesity group compared with control participants (p < 0.001). A top-down cortical model best explained our functional magnetic resonance imaging data (posterior probability = 86%). Participants at higher BMI were less effective at inhibiting activity in the amygdala via the orbitofrontal cortex and dorsomedial prefrontal cortex during reappraisal compared with those at lower BMI. In contrast, increased excitatory modulation of dorsolateral prefrontal cortex-to-amygdalar connectivity was found in participants at lower BMI. CONCLUSIONS: These findings support a framework involving alterations in fronto-amygdalar connectivity contributing to difficulties in regulating negative affect in individuals at higher weight.

Association of anandamide and 2-arachidonoylglycerol concentrations with clinical features and body mass index in eating disorders and obesity.

BACKGROUND: Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a pivotal role in stimulating motivational behavior toward food and energy metabolism. Aberrant functioning of the endocannabinoid system has been observed in extreme weight conditions (EWCs), suggesting it may influence pathophysiology. Then, we aimed to analyze fasting AEA and 2-AG plasma concentrations among individuals with EWC (i.e., anorexia nervosa [AN] and obesity with and without eating disorders [EDs]) compared with healthy controls (HCs), and its association with clinical variables and body mass index (BMI). METHODS: The sample included 113 adult women. Fifty-seven belonged to the obesity group, 37 without EDs (OB-ED) and 20 with ED (OB+ED classified within the binge spectrum disorders), 27 individuals from the AN group, and 29 from the HC group. Peripheral blood samples, several clinical variables, and BMI were evaluated. RESULTS: Unlike 2-AG, AEA concentrations showed significant differences between groups (p < 0.001). Increased AEA was observed in the OB-ED and OB+ED compared with both HC and AN group, respectively. Likewise, AEA was differentially associated with emotional dysregulation, general psychopathology, food addiction, and BMI in all clinical groups. CONCLUSIONS: These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches.

Diseño y aplicación de un cuestionario de detección precoz en salud mental infantil / Design and application of an early detection questionnaire in child mental health

Los problemas en salud mental infantil son frecuentes, complejos y pueden conllevar un riesgo en el desarrollo. La prevención en salud mental es un compromiso colectivo, especialmente por parte de las instituciones que atienden la primera infancia: la escuela y la consulta pediátrica. El objetivo de esta investigación es validar un instrumento diseñado ad hoc de detección precoz en salud mental para la primera infancia. En el diseño del instrumento, denominado Detectar para Prevenir–Salud Mental Infantil–25 (DxP-SMI-25), se tuvo en cuenta la literatura previa y las limitaciones actuales en la detección precoz en salud mental. El contenido del cuestionario se validó mediante un juicio de expertos y se aplicó el cuestionario, junto al Ages & Statges Questionnaires: Social-Emotional-2, con el fin de obtener la validez de criterio. El instrumento diseñado muestra una buena predisposición y permite una evaluación global del desarrollo.

Child mental health problems are frequent, complex and can lead to developmental risk. Prevention in mental health is a collective commitment, especially on the part of the institutions that care for early childhood: the school and the pediatric office. The aim of this paper is to validate an ad hoc instrument designed for early mental health screening in early childhood. The design of the instrument, called Detectar para Prevenir- Salud Mental Infantil-25 (DxP-SMI-25, Detect to Prevent- Children's Mental Health-25), took into account previous literature and current limitations in early mental health screening. The content of the questionnaire was validated by means of expert judgment and the questionnaire was applied, together with the Ages & Statges Questionnaires: Social-Emotional-2, in order to obtain criterion validity. The designed instrument shows a good predisposition and allows a global assessment of development.

Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey.

BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1-2, 2-3 and >3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.

The neural correlates of delay discounting in obesity and binge eating disorder.

BACKGROUND AND AIMS: Increased delay discounting is associated with obesity and binge eating disorder (BED). Although BED and obesity frequently co-occur, the neural mechanisms underlying delay discounting in these conditions remain poorly understood. METHODS: Thirtyfive women with obesity, including 10 participants with obesity and BED and 31 controls completed a monetary delay discounting task during functional magnetic resonance imaging. RESULTS: We identified that increased discounting rates were associated with decreased activity in the left anterior insula in participants with obesity compared to controls when choosing immediate rewards over delayed rewards (PFWE < 0.05). An exploratory analysis comparing the BED subsample to the other groups did not detect significant differences. DISCUSSION AND CONCLUSIONS: Our findings suggest decreased activity in the anterior insula may underlie heightened delay discounting in individuals with obesity, contributing the probability of choosing immediate rewards over delayed rewards based on emotional states. Future studies including larger, more diverse samples are required to confirm these effects.

Adequacy of nutritional support using computed tomography (CT) in patients with head and neck cancer (HNC) during chemo-radiotherapy (CRT).

We assessed forty HNC patients receiving treatment with curative intent. Specific quantitative muscle and fat changes were evaluated using CT. Nutrition support was provided according to ESPEN guidelines, with adjusted body weight (ABW) in overweight/obese patients used to define their nutritional targets. Linear regression models were used to evaluate clinical predictors of tissue loss. Mean overall losses were body weight (-10.5%), and CT-defined muscle (-8.4%) and fat mass (-24.8%), p < 0.001. A subset of 20 patients had high muscle loss (-14.7%) with concurrent negative energy balance as reflected by considerable fat loss (-29.7%); those tended to have higher baseline body mass index (26.2 vs. 23.3 kg/m2, p = 0.063). In multivariate regression, only ABW independently predicted muscle loss (p < 0.001) and fat loss (p = 0.002). Nutrition support according to guidelines was appropriate for a subset of patients. ABW use to set nutrition targets in overweight/obese patients would appear to be insufficient, based on large tissue losses.

Role of Gastrointestinal Hormones as a Predictive Factor for Long-Term Diabetes Remission: Randomized Trial Comparing Metabolic Gastric Bypass, Sleeve Gastrectomy, and Greater Curvature Plication.

PURPOSE: Long-term studies comparing the mechanisms of different bariatric techniques for T2DM remission are scarce. We aimed to compare type 2 diabetes (T2DM) remission after a gastric bypass with a 200-cm biliopancreatic limb (mRYGB), sleeve gastrectomy (SG), and greater curvature plication (GCP), and to assess if the initial secretion of gastrointestinal hormones may predict metabolic outcomes at 5 years. MATERIAL AND METHODS: Forty-five patients with mean BMI of 39.4(1.9)kg/m2 and T2DM with HbA1c of 7.7(1.9)% were randomized to mRYGB, SG, or GCP. Anthropometric and biochemical parameters, fasting concentrations of PYY, ghrelin, glucagon, and AUC of GLP-1 after SMT were determined prior to and at months 1 and 12 after surgery. At 5-year follow-up, anthropometrical and biochemical parameters were determined. RESULTS: Total weight loss percentage (TWL%) at year 1 and GLP-1 AUC at months 1 and 12 were higher in the mRYGB than in the SG and GCP. TWL% remained greater at 5 years in mRYGB group - 27.32 (7.8) vs. SG - 18.00 (10.6) and GCP - 14.83 (7.8), p = 0.001. At 5 years, complete T2DM remission was observed in 46.7% after mRYGB vs. 20.0% after SG and 6.6% after GCP, p < 0.001. In the multivariate analysis, shorter T2DM duration (OR 0.186), p = 0.008, and the GLP-1 AUC at 1 month (OR 7.229), p = 0.023, were prognostic factors for complete T2DM remission at 5-year follow-up. CONCLUSIONS: Long-term T2DM remission is mostly achieved with hypoabsortive techniques such as mRYGB. Increased secretion of GLP-1 after surgery and shorter disease duration were the main predictors of T2DM remission at 5 years.

Long-Term Effects in Bone Mineral Density after Different Bariatric Procedures in Patients with Type 2 Diabetes: Outcomes of a Randomized Clinical Trial.

There is scant evidence of the long-term effects of bariatric surgery on bone mineral density (BMD). We compared BMD changes in patients with severe obesity and type 2 diabetes (T2D) 5 years after randomization to metabolic gastric bypass (mRYGB), sleeve gastrectomy (SG) and greater curvature plication (GCP). We studied the influence of first year gastrointestinal hormone changes on final bone outcomes. Forty-five patients, averaging 49.4 (7.8) years old and body mass index (BMI) 39.4 (1.9) kg/m2, were included. BMD at lumbar spine (LS) was lower after mRYGB compared to SG and GCP: 0.89 [0.82;0.94] vs. 1.04 [0.91;1.16] vs. 0.99 [0.89;1.12], p = 0.020. A higher percentage of LS osteopenia was present after mRYGB 78.6% vs. 33.3% vs. 50.0%, respectively. BMD reduction was greater in T2D remitters vs. non-remitters. Weight at fifth year predicted BMD changes at the femoral neck (FN) (adjusted R2: 0.3218; p = 0.002), and type of surgery (mRYGB) and menopause predicted BMD changes at LS (adjusted R2: 0.2507; p < 0.015). In conclusion, mRYGB produces higher deleterious effects on bone at LS compared to SG and GCP in the long-term. Women in menopause undergoing mRYGB are at highest risk of bone deterioration. Gastrointestinal hormone changes after surgery do not play a major role in BMD outcomes.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey.

BACKGROUND & AIMS: The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF). METHODS: In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions. RESULTS: HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001). CONCLUSIONS: This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care.

Changes in Bone Mineral Density in Patients with Type 2 Diabetes After Different Bariatric Surgery Procedures and the Role of Gastrointestinal Hormones.

BACKGROUND: To compare changes in bone mineral density (BMD) in patients with morbid obesity and type 2 diabetes (T2D) a year after being randomized to metabolic gastric bypass (mRYGB), sleeve gastrectomy (SG), and greater curvature plication (GCP). We also analyzed the association of gastrointestinal hormones with skeletal metabolism. METHODS: Forty-five patients with T2D (mean BMI 39.4 ± 1.9 kg/m2) were randomly assigned to mRYGB, SG, or GCP. Before and 12 months after surgery, anthropometric, body composition, biochemical parameters, fasting plasma glucagon, ghrelin, and PYY as well as GLP-1, GLP-2, and insulin after a standard meal were determined. RESULTS: After surgery, the decrease at femoral neck (FN) was similar but at lumbar spine (LS), it was greater in the mRYGB group compared with SG and GCP - 7.29 (4.6) vs. - 0.48 (3.9) vs. - 1.2 (2.7)%, p < 0.001. Osteocalcin and alkaline phosphatase increased more after mRYGB. Bone mineral content (BMC) at the LS after surgery correlated with fasting ghrelin (r = - 0.412, p = 0.01) and AUC for GLP-1 (r = - 0.402, p = 0.017). FN BMD at 12 months correlated with post-surgical fasting glucagon (r = 0.498, p = 0.04) and insulin AUC (r = 0.384, p = 0.030) and at LS with the AUC for GLP-1 in the same time period (r = - 0.335, p = 0.049). However, in the multiple regression analysis after adjusting for age, sex, and BMI, the type of surgery (mRYGB) remained the only factor associated with BMD reduction at LS and FN. CONCLUSIONS: mRYGB induces greater deleterious effects on the bone at LS compared with SG and GCP, and gastrointestinal hormones do not play a major role in bone changes.

What Difference Does it Make? Risk-Taking Behavior in Obesity after a Loss is Associated with Decreased Ventromedial Prefrontal Cortex Activity.

Altered activity in decision-making neural circuitry may underlie the maladaptive food choices found in obesity. Here, we aimed to identify the brain regions purportedly underpinning risk-taking behavior in individuals with obesity. Twenty-three adult women with obesity and twenty-three healthy weight controls completed the Risky Gains Task during functional magnetic resonance imaging (fMRI). This task allows participants to choose between a safe option for a small, guaranteed monetary reward and risky options with larger rewards. fMRI analyses comparing losing trials to winning trials found that participants with obesity presented decreased activity in the left anterior insula in comparison to controls (p < 0.05, AlphaSim corrected). Moreover, left insula activation during losses vs. wins was negatively correlated with UPPS-P questionnaire sensation seeking scores. During safe vs. risky trials following a loss, the control group exhibited increased activation in the ventromedial prefrontal cortex (vmPFC) (p < 0.05, AlphaSim corrected) in comparison to the OB group. Moreover, vmPFC response in the obesity group during post-loss trials was negatively correlated with risky choices on the task overall. As a whole, our findings support that diminished tuning of the insula towards interoceptive signals may lead to a lack of input to the vmPFC when weighing the costs and benefits of risky choices.

A multimodal MRI study of the neural mechanisms of emotion regulation impairment in women with obesity.

Maladaptive emotion regulation contributes to overeating and impedes weight loss. Our study aimed to compare the voluntary downregulation of negative emotions by means of cognitive reappraisal in adult women with obesity (OB) and female healthy controls (HC) using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Women with OB (n = 24) and HC (n = 25) carried out an emotion regulation task during functional MRI scanning. Seed-to-voxel resting-state connectivity patterns derived from activation peaks identified by this task were compared between groups. Diffusion tensor imaging (DTI) was used to examine white matter microstructure integrity between regions exhibiting group differences in resting-state functional connectivity. Participants in the OB group presented reduced activation in the ventromedial prefrontal (vmPFC) cortex in comparison to the HC group when downregulating negative emotions, along with heightened activation in the extrastriate visual cortex (p < 0.05, AlphaSim-corrected). Moreover, vmPFC peak activity levels during cognitive reappraisal were negatively correlated with self-reported difficulties in emotion regulation. OB patients exhibited decreased functional connectivity between the vmPFC and the temporal pole during rest (peak-pFWE = 0.039). Decreased fractional white-matter track volume in the uncinate fasciculus, which links these two regions, was also found in participants with OB. Taken together, our findings are indicative of emotion regulation deficits in OB being underpinned by dysfunctional hypoactivity in the vmPFC and hyperactivity in the extrastriate visual cortex. Our results provide a potential target circuit for neuromodulatory interventions to improve emotion regulation skills and weight-loss intervention outcomes.

Survival benefit of multidisciplinary care in amyotrophic lateral sclerosis in Spain: association with noninvasive mechanical ventilation.

PURPOSE: Multidisciplinary care has become the preferred model of care for patients with amyotrophic lateral sclerosis (ALS). It is assumed that the sum of interventions associated with this approach has a positive effect on survival. The objective of the study was to evaluate the impact of a multidisciplinary care approach on the survival of patients with ALS. PATIENTS AND METHODS: We performed a retrospective review of prospectively collected data in a tertiary referral center in Spain. Participants were patients with definite or probable ALS managed in a multidisciplinary care program. We compared demographic and survival data of patients with definite or probable ALS treated in a referral center without and with implementation of a multidisciplinary care program. We performed time-dependent multivariate survival analysis of the use of noninvasive mechanical ventilation (NIMV) and gastrostomy. RESULTS: We evaluated 398 consecutive patients, of whom 54 were treated by a general neurologist and 344 were treated in the multidisciplinary care clinic. Patients receiving multidisciplinary care were older (62 vs 58 years), tended to have bulbar onset disease (30% vs 17.7%), and were more likely to receive riluzole (88.7% vs 29.6%, p<0.01), NIMV (48.8% vs 29.6%, p>0.001), and nutrition via gastrostomy (32.3% vs 3.7%, p<0.01). Kaplan-Meier analysis showed a 6-month increase in survival (log-rank, 16.03, p<0.001). Application of the Andersen-Gill model showed that the variables associated with reduced mortality were reduced time to NIMV and gastrostomy and the duration of both, thus reflecting compliance. CONCLUSIONS: Multidisciplinary care increased the survival of ALS patients in our study population. Timely use of respiratory support and gastrostomy are fundamental aspects of this benefit.

Role of adipose tissue GLP-1R expression in metabolic improvement after bariatric surgery in patients with type 2 diabetes.

We aimed to explore the relationship between GLP-1 receptor (GLP-1R) expression in adipose tissue (AT) and incretin secretion, glucose homeostasis and weight loss, in patients with morbid obesity and type 2 diabetes undergoing bariatric surgery. RNA was extracted from subcutaneous (SAT) and visceral (VAT) AT biopsies from 40 patients randomized to metabolic gastric bypass, sleeve gastrectomy or greater curvature plication. Biochemical parameters, fasting plasma insulin, glucagon and area under the curve (AUC) of GLP-1 following a standard meal test were determined before and 1 year after bariatric surgery. GLP-1R expression was higher in VAT than in SAT. GLP-1R expression in VAT correlated with weight (r = -0.453, p = 0.008), waist circumference (r = -0.494, p = 0.004), plasma insulin (r = -0.466, p = 0.007), and systolic blood pressure (BP) (r = -0.410, p = 0.018). At 1 year, GLP-1R expression in VAT was negatively associated with diastolic BP (r = -0.361, p = 0.039) and, following metabolic gastric bypass, with the increase of GLP-1 AUC, (R2 = 0.46, p = 0.038). Finally, GLP-1R in AT was similar independently of diabetes outcomes and was not associated with weight loss after surgery. Thus, GLP-1R expression in AT is of limited value to predict incretin response and does not play a role in metabolic outcomes after bariatric surgery.