Weight loss benefits on HDL cholesterol persist even after weight regaining.

BACKGROUND: Obesity-related comorbidities may relapse in patients with weight regain after bariatric surgery. However, HDL cholesterol (HDLc) levels increase after surgery and seem to remain stable despite a gradual increase in BMI. The aim of this study is to analyze the effects of weight regain after bariatric surgery on HDL cholesterol. MATERIALS AND METHODS: This is a retrospective, observational, cohort study in patients who underwent bariatric surgery in the Hospital de la Santa Creu i Sant Pau (Barcelona) between 2007 and 2015. Patients without at least 5 years of follow-up after surgery, under fibrate treatment, and those who required revisional surgery were excluded from the analysis. Data were collected at baseline, 3 and 6 months after surgery, and then annually until 5 years post-surgery. RESULTS: One hundred fifty patients were analyzed. 93.3% of patients reached > 20% of total weight loss after surgery. At 5th year, 37% of patients had regained > 15% of nadir weight, 60% had regained > 10%, and 22% had regained < 5% of nadir weight. No differences were found in HDLc levels between the different groups of weight regain, nor in the % of change in HDLc levels between nadir weight and 5 years, or in the proportion of patients with normal HDLc concentrations either. CONCLUSION: HDLc remains stable regardless of weight regain 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.

Significado pronóstico de los niveles de albúmina previos al tratamiento en los pacientes con carcinoma escamoso de cabeza y cuello / Prognostic significance of albumin levels prior to treatment in patients with head and neck squamous cell carcinoma

INTRODUCCIÓN Y OBJETIVOS: Los niveles de albúmina pretratamiento han demostrado tener valor pronóstico en pacientes oncológicos. El objetivo del presente estudio es analizar la relación entre las cifras de albúmina pretratamiento y el pronóstico en pacientes con un carcinoma escamoso de cabeza y cuello (CECC). MÉTODOS: Estudio retrospectivo de una cohorte de 741 pacientes con CECC con una determinación de albúmina plasmática dentro de las 4 semanas previas al inicio del tratamiento. Se analizó la relación entre la supervivencia específica y los niveles de albúmina mediante un análisis de partición recursiva. RESULTADOS: Los niveles de albúmina tuvieron una relación directamente proporcional y estadísticamente significativa con la supervivencia específica. De acuerdo con los resultados del análisis de partición recursiva, los puntos de corte con una mayor capacidad pronóstica fueron 37,5 y 46,1 g/l. En relación con los pacientes con albúmina > 46,1 g/l, los pacientes con albúmina entre 37,5 y 46,1 g/l contaron con un riesgo 1,44 veces superior de morir como consecuencia del tumor (IC 95%: 0,95-2,19, p = 0,081), y los pacientes con cifras de albúmina < 37,5 g/l, con un riesgo 3,19 veces superior (IC 95%: 2,01-5,04, p = 0,0001). Las diferencias en supervivencia en función del valor de albúmina se observaron de forma exclusiva en los pacientes con tumores avanzados (estadios III-IV). CONCLUSIÓN: Las concentraciones de albúmina plasmática previas al tratamiento son un factor pronóstico independiente de supervivencia en los pacientes con CECC en estadios avanzados (III-IV), siendo el punto de corte de 37,5 g/l el de mayor capacidad pronóstica

INTRODUCTION AND OBJECTIVES: Pre-treatment albumin levels have been shown to have prognostic capacity in oncological patients. The aim of this study is to analyse the relationship between albumin levels and prognosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a retrospective study in a cohort of 741 patients with HNSCC and a plasmatic albumin testing within the 4 weeks prior to the start of treatment. The relationship between disease-specific survival and plasma albumin levels was analysed by a recursive partitioning analysis. RESULTS: Albumin levels showed a directly proportional and statistically significant association with disease-specific survival. According to the results of the recursive partitioning analysis, the cut-off points with a higher prognostic capacity were 37.5 g/L and 46.1 g/L. Taking patients with albumin levels > 46.1 g/L as the benchmark, patients with albumin levels between 37.5-46.1 g/L had a 1.44 times higher risk of disease-specific death (95% CI: .95-2.19, P = .081), and patients with levels < 37.5 g/L had a 3.19 times higher risk (95% CI: 2.01-5.04, P = .0001). The differences in survival based on albumin levels were only seen in patients with advanced stage tumours (stages III-IV). CONCLUSION: Pre-treatment plasmatic albumin is an independent prognostic factor for patients with advanced stage HNSCC (III-IV), 37.5g/L being the cut-off point with the highest prognostic capacity

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity.

OBJECTIVES: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. METHODS: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. RESULTS: Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (ßstd = .42, P = .008) but not in children (ßstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. CONCLUSIONS: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity.

Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells.

BACKGROUND & AIMS: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.

Prognostic significance of albumin levels prior to treatment in patients with head and neck squamous cell carcinoma. / Significado pronóstico de los niveles de albúmina previos al tratamiento en los pacientes con carcinoma escamoso de cabeza y cuello.

INTRODUCTION AND OBJECTIVES: Pre-treatment albumin levels have been shown to have prognostic capacity in oncological patients. The aim of this study is to analyse the relationship between albumin levels and prognosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a retrospective study in a cohort of 741 patients with HNSCC and a plasmatic albumin testing within the 4weeks prior to the start of treatment. The relationship between disease-specific survival and plasma albumin levels was analysed by a recursive partitioning analysis. RESULTS: Albumin levels showed a directly proportional and statistically significant association with disease-specific survival. According to the results of the recursive partitioning analysis, the cut-off points with a higher prognostic capacity were 37.5g/L and 46.1g/L. Taking patients with albumin levels >46.1g/L as the benchmark, patients with albumin levels between 37.5-46.1g/L had a 1.44 times higher risk of disease-specific death (95%CI: .95-2.19, P=.081), and patients with levels <37.5g/L had a 3.19 times higher risk (95%CI: 2.01-5.04, P=.0001). The differences in survival based on albumin levels were only seen in patients with advanced stage tumours (stagesIII-IV). CONCLUSION: Pre-treatment plasmatic albumin is an independent prognostic factor for patients with advanced stage HNSCC (III-IV), 37.5g/L being the cut-off point with the highest prognostic capacity.

Mini nutritional assessment is a better predictor of mortality than subjective global assessment in heart failure out-patients.

BACKGROUND & AIMS: There is no consensus on the best method for nutritional screening and assessment in patients with heart failure (HF). This study aimed to determine which nutritional assessment method had the highest prognostic significance for patients with HF treated in outpatient clinics. We also aimed to identify a fast, reliable screening method for detecting malnutrition in these patients. METHODS: This prospective study included 151 subjects that attended an outpatient HF clinic at a university hospital. All patients completed three nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the MNA-short form (MNA-SF), and the Malnutrition Screening Tool (MST), and then, two nutritional assessment questionnaires: the Subjective Global Assessment (SGA) and the Mini Nutritional Assessment®(MNA). Patients were followed-up for 2 years. The primary endpoint was all-cause mortality. RESULTS: Malnutrition or nutritional risk was identified in 15.9% of patients with the SGA and in 25.1% of patients with the MNA. Age, New York Heart Association (NYHA) functional class, and MNA were the only independent all-cause death predictors after adjusting for age, gender, NYHA functional class, body mass index, Barthel index, 25-hydroxyvitamin D concentrations, treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, and treatment with beta-blockers. The SGA could not independently predict all-cause mortality in a multivariate analysis that included the same covariates. The MNA-SF had the best sensitivity, specificity, and kappa coefficient for screening malnutrition, based on the MNA and the SGA as references, compared to the other screening methods. CONCLUSIONS: In our cohort, malnutrition assessed by MNA, but not by SGA, was an independent predictor of mortality. MNA-SF showed remarkable sensitivity and specificity; thus, it might be a valuable tool for rapidly identifying malnutrition risk in outpatients with HF.

Low prevalence of non-alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been proposed as an independent cardiovascular risk factor. The present study evaluated the prevalence of NAFLD in a cohort of type 1 diabetic (T1D) patients and its potential relationship with subclinical cardiovascular disease (CVD). METHODS: One hundred T1D patients (mean [±SD] age 39.4 ± 7.8 years, disease duration 21.7 ± 8.6 years) were included in the present cross-sectional study. All subjects underwent abdominal ultrasonography for detection of NAFLD, carotid ultrasonography to measure the carotid intima-media thickness (CIMT) and atheroma plaques, and cardiac tomography for evaluation of the coronary artery calcium score (CACS). RESULTS: Of the study cohort, 12% had NAFLD and 23% had a CACS >0. The T1D subjects with NAFLD had a greater CIMT than those without NAFLD (0.65 ± 0.17 vs 0.55 ± 0.14 mm; P = 0.029), but there were no significant differences between the two groups with regard to CACS, glycemic control, or the presence of carotid plaques. Patients with high liver enzyme concentrations (>20 U/L) had a higher CIMT (0.60 ± 0.16 vs 0.54 ± 0.13; P = 0.04) and there was a higher proportion of altered CACS (17 [73.9%] vs 6 [26.1%]; P = 0.001) and detection of carotid plaques (10 [76.9%] vs 3 [23.1%]; P = 0.014) in this group. CONCLUSIONS: A low prevalence of NAFLD was found in the T1D cohort that was associated globally with a low proportion of abnormal CVD imaging markers, although these imaging parameters were worse in subjects in whom NAFLD was detected.

Evaluation of Vitamin and Trace Element Requirements after Sleeve Gastrectomy at Long Term.

BACKGROUND: Nutritional deficiencies are common after bariatric surgery, but data are scarce after sleeve gastrectomy (SG) at long term. METHODS: We performed a prospective nutritional status evaluation before and at 2 and 5 years after SG in morbid obese patients receiving mulvitamin and mineral supplementation at a Spanish university hospital. One hundred seventy-six patients (49.3 ± 9.1 years and 46.7 ± 7.4 kg/m2) were evaluated; 51 of them were followed during 5 years. Anthropometric, compliance supplementation intake, and micronutrient evaluation were performed. RESULTS: Baseline concentrations were below normal values for 25(OH) vitamin D (73%), folic acid (16.5%), cobalamin (6.9%), pyridoxine (12%), thiamine (3.4%), and copper (0.5%). Anemia was found in 23%. In 49% of the subjects, at least one micronutrient deficiency was found at 2 years after SG. Vitamin D deficiency persisted at 2 and 5 years higher than 30% of patients. Frequencies of deficiencies for folic acid, B12, B6, and B1 vitamins decreased significantly after 2 years with normalization at 5 years. Copper deficiency increased between 1 and 2 years and it persisted at 5 years after SG. Vitamin supplementation compliance decreased progressively from the first year after surgery (94.8 to 81% at 2 years and to 53% 5 years after surgery). CONCLUSIONS: Vitamin D deficiency is the most prevalent long-term nutritional deficiency after SG. About half of patients show some micronutrient deficiency at medium long term, despite supplementation. A proactive follow-up is required to ensure a personalized and adequate supplementation in all surgically treated obese patients including those in which SG has been performed.

Obestatin does not modify weight and nutritional behaviour but is associated with metabolic syndrome in old women.

OBJECTIVE: Ghrelin and obestatin have apparent opposite orexigenic and anorexigenic effects, although the latter has not been firmly demonstrated in humans. So far, little data have been reported in relation to its potential association with metabolic syndrome (MS). The objective was to study obestatin concentrations in relation to nutritional parameters and eating behaviours in old women. DESIGN, PATIENTS AND MEASUREMENTS: Prospective study; a total of 110 women (age: 76.93 ± 6.32) from the Mataró Ageing Study were included. Individuals were characterized by anthropometric variables, lipids, glucose, blood pressure, MS components (Adult Treatment Panel III criteria), anorexia and nutritional status by Mini Nutritional Assessment Short Form (MNA-SF) and re-evaluated at 2-year follow-up. Obestatin was measured by IRMA. RESULTS: 58.2% of the subjects had MS; at 2-year follow-up 24.1% had a weight loss >5%, 7.2% >10%, and 26.4% changed their MNA-SF score to risk of malnutrition category. Anorexia was present in 38.4%. Obestatin levels were not related to either change of weight, MNA-SF or anorexia, but a positive correlation was found with the absolute difference between basal and 2-year waist circumference (WC) (r = 0.429; P < 0.001) and relative difference between basal and 2-year WC (r = 0.420; P < 0.001); both remained significant after adjusting for age and body mass index. When obestatin was divided into quartiles, a significant lineal trend was observed in relation to WC (P = 0.049), absolute and relative difference between basal and 2-year WC (both P < 0.001). Obestatin was associated with glucose impairment (69.0% in 4th quartile vs 47.5% in 1st to 3rd, P = 0.047; after adjustment, P = 0.098) and MS (77.8% in 4th vs 51.3% in 1st to 3rd, P = 0.017; after adjustment, P = 0.046, OR 2.90 (1.02-8.25) 4th vs 1st to 3rd). CONCLUSIONS: Obestatin is elevated in aged women bearing MS but is otherwise not associated with other nutritional parameters, weight loss or anorexia.

Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.