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/m(2), 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) (adjustedR(2): 0.3218;p= 0.002), and type of surgery (mRYGB) and menopause predicted BMD changes at LS (adjustedR(2): 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

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, (R-2 = 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

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

Fish Oil Enriched Intravenous Lipid Emulsions Reduce Triglyceride Levels in Non-Critically Ill Patients with TPN and Type 2 Diabetes. A Post-Hoc Analysis of the INSUPAR Study

There are no studies that have specifically assessed the role of intravenous lipid emulsions (ILE) enriched with fish oil in people with diabetes receiving total parenteral nutrition (TPN). The objective of this study was to assess the metabolic control (glycemic and lipid) and in-hospital complications that occurred in non-critically ill inpatients with TPN and type 2 diabetes with regard to the use of fish oil emulsions compared with other ILEs. We performed a post-hoc analysis of the Insulin in Parenteral Nutrition (INSUPAR) trial that included patients who started with TPN for any cause and that would predictably continue with TPN for at least five days. The study included 161 patients who started with TPN for any cause. There were 80 patients (49.7%) on fish oil enriched ILEs and 81 patients (50.3%) on other ILEs. We found significant decreases in triglyceride levels in the fish oil group compared to the other patients. We did not find any differences in glucose metabolic control: mean capillary glucose, glycemic variability, and insulin dose, except in the number of mild hypoglycemic events that was significantly higher in the fish oil group. We did not observe any differences in other metabolic, liver or infectious complications, in-hospital length of stay or mortality

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

Abstract 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

La enseñanza del metabolismo: retos y oportunidades

En el marco del Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-163, cuya descripción y resultados incluimos, decidimos que esta era una excelente oportunidad para reflexionar acerca de la enseñanza del metabolismo y de poner por escrito dichas reflexiones en un libro. Quisimos y pudimos contar con la colaboración de buena parte de los compañeros del Departamento de Biología Molecular y Bioquímica que apoyaron con su firma el proyecto PIE15-163 y extendimos nuestra invitaciones a otros compañeros de dentro y fuera de la Universidad de Málaga. Del Departamento de Biología Molecular y Bioquímica de la Universidad de Málaga hemos recibido aportaciones de los catedráticos Victoriano Valpuesta Fernández, Ana Rodríguez Quesada y Antonio Heredia Bayona, los profesores titulares María Josefa Pérez Rodríguez, José Luis Urdiales Ruiz e Ignacio Fajardo Paredes y la investigadora postdoctoral y profesora sustituta interina Beatriz Martínez Poveda. De otros departamentos de la Universidad de Málaga hemos contado con las aportaciones de la catedrática del Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología Pilar Morata Losa, del catedrático del Departamento de Lenguajes y Ciencias de la Computación José Francisco Aldana Montes y los componentes de su grupo de investigación Khaos Ismael Navas Delgado, María Jesús García Godoy, Esteban López Camacho y Maciej Rybinski, del catedrático Ángel Blanco López, del Área de Conocimiento de Didáctica de las Ciencias Experimentales y del Doctor en Ciencias Químicas y actual doctorando del Programa de Doctorado "Educación y Comunicación Social" Ángel Luis García Ponce. De fuera de la Universidad de Málaga, hemos contado con las aportaciones del catedrático de la Universidad de La Laguna Néstor V. Torres Darias, de la catedrática de la Universitat de les Illes Balears Pilar Roca Salom y de sus compañeros los profesores Jorge Sastre Serra y Jordi Oliver, de los catedráticos de la Universidad de Granada Rafael Salto González y María Dolores Girón González y su colaborador el Dr. José Dámaso Vílchez Rienda, del profesor titular de la Universidad de Alcalá Ángel Herráez, del investigador postdoctoral de la Universidad de Erlangen (Alemania) Guido Santos y del investigador postdoctoral de la empresa Brain Dynamics Carlos Rodríguez Caso.Hemos estructurado los contenidos del libro en diversas secciones. La primera presenta el Proyecto en cuyo marco se ha gestado la iniciativa que ha conducido a la edición del presente libro. La segunda sección la hemos titulado "¿Qué metabolismo?" e incluye diversas aportaciones personales que reflexionan acerca de qué metabolismo debe conocer un graduado en Bioquímica, en Biología, en Química, en Farmacia o en Medicina, así como una aportación acerca de qué bioquímica estructural y enzimología son útiles y necesarias para un estudiante que vaya a afrontar el estudio del metabolismo. La tercera sección, "Bases conceptuales", analiza las aportaciones del aprendizaje colaborativo, el contrato de aprendizaje y el aprendizaje basado en la resolución de casos prácticos a la mejora del proceso enseñanza-aprendizaje dentro del campo de la Bioquímica y Biología Molecular, más concretamente en el estudio del metabolismo. La cuarta sección se titula "Herramientas", es la más extensa e incluye las diversas aportaciones centradas en propuestas concretas de aplicación relevantes y útiles para la mejora de la docencia-aprendizaje del metabolismo. Sigue una sección dedicada a presentar de forma resumida los "Resultados" del proyecto PIE15-163. El libro concluye con una "coda final" en la que se reflexiona acerca del aprendizaje de la Química a la luz de la investigación didáctica.Patrocinado por el Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-16

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

ObjectiveTo 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 methodsProspective 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.ResultsThirteen 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&lt;0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P&lt;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.ConclusionsPatients 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

Altres ajuts: This manuscript and research were co-funded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. Additional support was received from the Delegación del Gobierno para el Plan Nacional sobre Drogas (2021I031). This work was partially supported by Instituto de Salud Carlos III through the grant CM21/00172 (IB) (co-funded by European Social Fund. ESF investing in your future). RG is supported by the Catalan Institution for Research and Advanced Studies (ICREA-Academia, 2021-Programme). TS is supported by a National Health and Medical Research Council (NHMRC)/Medical Research Future Fund (MRFF) Investigator Grant (MRF1193736), a Brain & Behavior Research Foundation (BBRF) Young Investigator Grant, and a University of Melbourne McKenzie Fellowship.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; p < 0.001) and the left supplementary motor area (NAcc-SMA; p < 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

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

Altres ajuts: This manuscript and research were supported by grants from the Delegación del Gobierno para el Plan Nacional sobre Drogas (2021I031) and cofounded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. CIBER Obn, CIBERSAM, and CIBERDEM are initiatives of ISCIII. This study has also been funded by Instituto de Salud Carlos III through the grant CM21/00172 (IB) (Co-funded by European Social Fund. ESF investing in your future). RG is supported by the Catalan Institution for Research and Advanced Studies. (ICREA-Academia, 2021-Programme)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). 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. 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. These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches

Clinical management of the acute complications of sickle cell anemia: 11 years of experience in a tertiary hospital

Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vacci-nation schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recog-nition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management