Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients.

Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J (apoJ). EAT explants were obtained from nondiabetic patients (ND), diabetic patients without coronary disease (DM), and DM patients with coronary disease (DM-C) after heart surgery. Morphological characteristics and gene expression were evaluated. Explants were cultured for 24 h and the content of nonesterified fatty acids (NEFA) and sphingolipid species in secretomes was evaluated by lipidomic analysis. Afterwards, secretomes were added to AC16 human cardiomyocytes for 24 h in the presence or absence of cardioprotective molecules (apoJ and HDL). Cytokine release and apoptosis/necrosis were assessed by ELISA and flow cytometry. The EAT from the diabetic samples showed altered expression of genes related to lipid accumulation, insulin resistance, and inflammation. The secretomes from the DM samples presented an increased ratio of pro/antiatherogenic ceramide (Cer) species, while those from DM-C contained the highest concentration of saturated NEFA. DM and DM-C secretomes promoted inflammation and cytotoxicity on AC16 cardiomyocytes. Exogenous Cer16:0, Cer24:1, and palmitic acid reproduced deleterious effects in AC16 cells. These effects were attenuated by exogenous apoJ. Diabetic secretomes promoted inflammation and cytotoxicity in cardiomyocytes. This effect was exacerbated in the secretomes of the DM-C samples. The increased content of specific NEFA and ceramide species seems to play a key role in inducing such deleterious effects, which are attenuated by apoJ.

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.

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes.

Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.

LDL binding to cell receptors and extracellular matrix is proatherogenic in obesity but improves after bariatric surgery.

Obesity is a major global public health issue involving dyslipidemia, oxidative stress, inflammation, and increased risk of CVD. Weight loss reduces this risk, but the biochemical underpinnings are unclear. We explored how obesity and weight loss after bariatric surgery influence LDL interactions that trigger proatherogenic versus antiatherogenic processes. LDL was isolated from plasma of six patients with severe obesity before (basal) and 6-12 months after bariatric surgery (basal BMI = 42.7 kg/m2; 6-months and 12-months postoperative BMI = 34.1 and 30 kg/m2). Control LDL were from six healthy subjects (BMI = 22.6 kg/m2). LDL binding was quantified by ELISA; LDL size and charge were assessed by chromatography; LDL biochemical composition was determined. Compared to controls, basal LDL showed decreased nonatherogenic binding to LDL receptor, which improved postoperatively. Conversely, basal LDL showed increased binding to scavenger receptors LOX1 and CD36 and to glycosaminoglycans, fibronectin and collagen, which is proatherogenic. One year postoperatively, this binding decreased but remained elevated, consistent with elevated lipid peroxidation. Serum amyloid A and nonesterified fatty acids were elevated in basal and postoperative LDL, indicating obesity-associated inflammation. Aggregated and electronegative LDL remained elevated, suggesting proatherogenic processes. These results suggest that obesity-induced inflammation contributes to harmful LDL alterations that probably increase the risk of CVD. We conclude that in obesity, LDL interactions with cell receptors and extracellular matrix shift in a proatherogenic manner but are partially reversed upon postoperative weight loss. These results help explain why the risk of CVD increases in obesity but decreases upon weight loss.

Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese.

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and γBB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients.

Obesity Surgery Improves Hypogonadism and Sexual Function in Men without Effects in Sperm Quality.

(1) Background: Obesity is associated with hypogonadism, sexual dysfunction, and impaired fertility in men. However, its effects on semen parameters or sexual function remain debatable. (2) Methods: This paper involves a longitudinal study in men submitted for obesity surgery at a university tertiary hospital. Patients were studied at baseline and at 6, 12, and 18 months after obesity surgery. At each visit, anthropometry measures were collected and hormonal and semen parameters were studied. Sexual function was evaluated with the International Index of Erectile Function (IIEF). (3) Results: A total of 12 patients were included. The average body mass index of patients decreased from 42.37 ± 4.44 to 29.6 ± 3.77 kg/m2 at 18 months after surgery (p < 0.05). Hormonal parameters improved after obesity surgery. The proportion of sperm cells with normal morphology tended to decrease from baseline and became most significant at 18 months (5.83 ± 4.50 vs. 2.82 ± 2.08). No significant changes were found in the remaining semen parameters. Erectile function improved significantly at six months after surgery. (4) Conclusions: The authors believe that, in general, the effects of obesity surgery on fertility may be limited or even deleterious (at least in the short and midterm follow-up).

Is Sleeve Gastrectomy as Effective in Older Patients as in Younger Patients? A Comparative Analysis of Weight Loss, Related Comorbidities, and Medication Requirements.

BACKGROUND: Bariatric surgery in the older population has been the subject of ongoing debate but several studies have recently demonstrated its short-term advantages in this age group. It is not yet clear, however, whether these benefits are long-lasting. METHODS: We retrospectively analyzed patients with morbid obesity who underwent laparoscopy sleeve gastrectomy (LSG). These patients were divided into two groups: those above 60 years of age (older group) and those of 60 years or under (younger group). Variables evaluated included demographics and anthropometrics data, comorbidities, and daily medication requirements. RESULTS: Two hundred fifty-two patients underwent LSG, 57 in the older group and 195 in the younger group. Outcomes related to weight loss in the older subjects were modest compared to those in the younger population (older group %EWL 41.6 vs younger group %EWL 51.1, p < 0.05, older group %TWL 24.9% vs younger group %TWL 25.2%, p < 0.05). During follow-up, both older and younger patients showed an improvement in all the comorbidities: hypertension (older 82.5% vs 38.1%, younger 52.6% vs 29.2%, p < 0.05), type 2 diabetes mellitus (older 38.6% vs 27.3%, 34.9% vs 23.9%, p < 0.05), hyperlipidemia (older 75.4% vs 42.9%, younger 35.9% vs 21.1%, p < 0.05), and OSAHS (older 57.9% vs 30%, younger 40.4% vs 7.1%, p < 0.05). The average number of daily medications used to manage comorbidities decreased in both groups. CONCLUSION: LSG in older patients is effective in terms of weight loss, improvement of comorbidities, and lower daily medication requirements up to 5 years of follow-up.

Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity.

The effect of bariatric surgery on lipid profile and the qualitative characteristics of lipoproteins was analyzed in morbidly obese subjects. Thirteen obese patients underwent bariatric surgery. Plasma samples were obtained before surgery and at 6 and 12 months after the intervention. Thirteen healthy subjects comprised the control group. Lipid profile, hsCRP, and the composition and functional characteristics of VLDL, LDL, and HDL were assessed. At baseline, plasma from subjects with obesity had more triglycerides, VLDLc, and hsCRP, and less HDLc than the control group. These levels progressively normalized after surgery, although triglyceride and hsCRP levels remained higher than those in the controls. The main differences in lipoprotein composition between the obese subjects and the controls were increased apoE in VLDL, and decreased cholesterol and apoJ and increased apoC-III content in HDL. The pro-/anti-atherogenic properties of LDL and HDL were altered in the subjects with obesity at baseline compared with the controls, presenting smaller LDL particles that are more susceptible to modification and smaller HDL particles with decreased antioxidant capacity. Bariatric surgery normalized the composition of lipoproteins and improved the qualitative characteristics of LDL and HDL. In summary, patients with obesity present multiple alterations in the qualitative properties of lipoproteins compared with healthy subjects. Bariatric surgery reverted most of these alterations.

Effectiveness of Bariatric Surgery in Patients with the Metabolically Healthy Obese Phenotype.

BACKGROUND: To evaluate the effectiveness and safety of bariatric surgery in metabolically healthy obese (MHO) patients. METHODS: In this retrospective, observational study, we reviewed the medical records of patients who underwent bariatric surgery at a tertiary care hospital between January 2007 and March 2015. Patients who underwent revisional surgery and patients with type 1 diabetes were excluded from the analysis. MHO patients were defined as those without a previous diagnosis of diabetes or atherogenic dyslipidemia and absence of hypoglycemic treatment or treatment with fibrates. RESULTS: A total of 188 patients were included (mean age 48.97 ± 10.32 years, 68.6% of women). Sleeve gastrectomy was performed in 121 patients (64%) and a gastric bypass in 67 patients (36%). Prior to surgery, 36 patients (19%) were MHO. In the second- and third-year post-surgery, MHO patients presented a higher percentage of total weight loss (%TWL) (35.16% vs. 30.34%; p = 0.02 and 33.97% vs. 27.78%; p = 0.013 respectively). Multiple regression analysis showed that MHO was associated with a higher weight loss irrespective of age, sex, baseline BMI, and type of surgery. We did not detect any differences in acute complications between patients with and without MHO after bariatric surgery. CONCLUSIONS: Bariatric surgery in MHO patients in our study was associated with higher weight loss than that in MUHO patients. There were no differences between the two groups in respect to acute complications following surgery.

The SEEN comprehensive clinical survey of adult obesity: Executive summary. / Abordaje clínico integral SEEN de la obesidad en la edad adulta: resumen ejecutivo.

Obesity is one of the great challenges in healthcare nowadays with important implications for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.seen.es, and that has been agreed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), together with the Nutrition Area (NutriSEEN) and the Working Group of Endocrinology, Nutrition and Physical Exercise (GENEFSEEN).

New Metrics to Assess Type 2 Diabetes After Bariatric Surgery: The "Time-Within-Remission Range".

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m2) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy.

Effects of Bariatric Surgery on HDL Cholesterol.

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDLc) are independent predictive factors of coronary heart disease. Bariatric surgery increases HDLc concentration, but the chronology and predictors of this improvement in HDLc levels are not well-established. The aim of the present study was to analyse the changes over time in HDLc concentrations after bariatric surgery and to determine the predictors of their increase. SUBJECTS AND METHODS: This was a retrospective, observational study. The medical records of patients who had undergone bariatric surgery at a tertiary care hospital between January 2007 and March 2015 were reviewed. Patients who underwent revisional surgery or were treated with fibrates were excluded from the analysis. RESULTS: A total of 185 patients were included in the study. Follow-up rates were as follows: 87% (year 2) and 28% (year 5). At postoperative month 3, HDLc levels decreased significantly versus baseline (- 11.1%; p = 0.000), at which point they began to rise, reaching their maximum level 2 years after bariatric surgery (26.2% increase from baseline; p = 0.000). The increase in HDLc concentration 2 years after surgery correlated with the preoperative HDLc level (r = - 0.292, p = 0.001), and it was greater in patients who underwent sleeve gastrectomy versus gastric bypass (0.36 ± 0.4 vs. 0.18 ± 0.4 mmol/L, respectively; p = 0.018). CONCLUSION: Bariatric surgery has a beneficial effect on HDLc levels. The maximum increase in postoperative HDLc concentrations is observed 2 years after surgery. Preoperative HDLc and the type of surgery are both significant predictors of the maximum increase in HDLc levels.

Assessing Motivational Stages and Processes of Change for Weight Management Around Bariatric Surgery: a Multicenter Study.

INTRODUCTION/PURPOSE: The assessment of the patients' motivation as a predictor of behavioral change via five stages (pre-contemplation, contemplation, preparation, action, and maintenance) and four processes (emotional re-evaluation, weight management actions, environmental restructuring, and weight consequences evaluation) of change. MATERIALS/METHODS: A total of 542 participants (251 waiting for bariatric surgery (BS), 90 undergoing BS, and 201 controls) completed the Stages (S-Weight) and Processes (P-Weight) of Change in Overweight and Obese People questionnaires in a multicenter cross-sectional study. RESULTS: A higher percentage of subjects seeking BS (31.7%) were in the action stage (16.7% of post-BS patients, p < 0.001; 14.9% of controls, p < 0.001). The referred body mass index (BMI) reduction was higher in subjects in active stages (3.6 ± 4.4 kg/m2 in maintenance versus 1.4 ± 1.4 kg/m2 in contemplation, p < 0.001). In the P-Weight questionnaire, patients looking for BS scored significant higher in the four processes of change than controls. In addition, a positive and significantly correlation between BMI and the four processes was observed. In the stepwise multivariate analysis, BMI and the S-Weight allocation were constantly associated with the four processes of change. CONCLUSION: Obesity is accompanied by a modifying behavioral stage, suggesting that subjects before BS are seriously thinking about overcoming excess weight. To identify subjects on the waiting list for BS who will be more receptive to weight lost interventions remains a challenge.

Outcomes of Bariatric Surgery in Patients with Cirrhosis.

CONTEXT: Information concerning the risk-benefit profile of bariatric surgery in subjects with liver cirrhosis is scarce. Our aim was to describe the long-term outcomes of bariatric surgery in a cohort of patients with liver cirrhosis submitted to bariatric surgery. METHODS: This was a multicenter, retrospective observational study performed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), with a review of patients with cirrhosis who had undergone bariatric surgery during the period from April 2004 to March 2017 in ten public reference hospitals in Spain. RESULTS: Data on 41 patients with cirrhosis submitted to obesity surgery were collected (mean age 53.8 ± 7.9 years, 46.3% women, presurgical BMI 45 ± 8.3 kg/m2). All but one patient belonged to Child-Pugh class A, and sleeve gastrectomy was conducted in 68.3% of cases. Percentage of total weight loss (%TWL) was 26.33 ± 8.3% and 21.16 ± 15.32% at 1 and 5 years after surgery, respectively. This was accompanied by a significant reduction of type 2 diabetes, high blood pressure, and dyslipidemia and by an improvement of liver enzymes over time. Model for End-Stage Liver Disease (MELD) index increased from 7.2 ± 1.9 to 9.8 ± 4.6 after 5 years. Seven patients (17%) developed early postsurgical complications. No postsurgical mortality was observed. During follow-up, only five patients developed liver decompensation. CONCLUSIONS: Bariatric surgery in selected patients with liver cirrhosis has metabolic benefits that could have a positive impact on liver prognosis. TRIAL REGISTRATION: Controlledtrials.com Identifier: 10.1186/ISRCTN15009106.

Influence of antrum size on gastric emptying and weight-loss outcomes after laparoscopic sleeve gastrectomy (preliminary analysis of a randomized trial).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has increased in popularity in recent years as a definitive bariatric procedure. Despite its growing popularity worldwide, the surgical technique is not well standardized. There is a lack of evidence on the matter of the antrum size and its relation to gastric emptying and weight-loss outcomes. The aim of the study is to evaluate the influence of antrum size over gastric emptying and weight-loss outcomes. METHODS: Twenty-five patients were prospectively randomized according to the distance between the first firing and the pylorus: AR group (antrum resection-2 cm from the pylorus) and AP group (antrum preservation-5 cm from the pylorus). Gastric emptying (%GE) was evaluated by a gastric emptying scintigraphy before surgery, 2 months and 1 year after LSG. Antrum volume was measured using a MultiSlice CT Scan performed 2 months and 1 year after surgery. The percent of excess weight loss (%EWL) was calculated after 1 year follow-up. RESULTS: At 2 months after LSG the mean %GE was 69.7 ± 18 in the AR group and 72.8 ± 20 in the AP group (p = 0.69). At 1 year it was 66.5 ± 21 and 74.2 ± 16 in the AR and AP groups, respectively (p = 0.30). A significant accelerated gastric emptying was observed at 2 months (p = 0.025) and at 1 year (p = 0.013) in the AP group. Meanwhile in the AR group this increase was not significant (p = 0.12 at 2 months and p = 0.21 at 1 year). Differences regarding the %EWL between groups were no statistically significant (p = 0.74). CONCLUSIONS: After LSG there is a global tendency to an accelerated gastric emptying, although only significant in the antrum preservation group; however, no differences were observed regarding the %EWL between groups after 1 year follow-up.

Long-Term Outcomes in Patients with Morbid Obesity and Type 1 Diabetes Undergoing Bariatric Surgery.

BACKGROUND: This study aims to describe the long-term outcomes of bariatric surgery in a cohort of patients with type 1 diabetes (T1DM). METHODS: Thirty-two patients with T1DM and initial BMI of 41.3 ± 4.8 kg/m2 were studied, 18.7 % undergoing duodenal switch (DS), 34.4 % gastric bypass, and 46.9 % sleeve gastrectomy and followed-up after surgery for 4.6 ± 2.6 years. Changes in BMI, HbA1c, insulin requirements, evolution of comorbidities, and microvascular complications were registered annually after surgery. RESULTS: Percentage of total weight loss (%TWL) 12 months after surgery was 30.4 ± 9.2 % and at 5 years, it decreased to 28.1 ± 11.5 % (p = 0.02). HbA1c was reduced during the first year from 8.5 ± 1.3 to 7.9 ± 1.4 %, p = 0.016. In the long-term, HbA1c returned to baseline values. There was a sustained reduction of 51 % in total daily insulin dose, and the decrease in the number of patients with hypertension, dyslipidemia, and obstructive sleep apnea was 42.8, 25, and 66 %, respectively. Retinopathy remained mainly unaffected, and 25 % of patients with microalbuminuria regressed to normoalbuminuria. CONCLUSIONS: Bariatric surgery in patients with T1DM mainly provides benefits of weight reduction, on insulin requirements, obesity comorbidities, and some benefits in diabetes complications, but might have only minimal effect on the glycemic control in the long term. This trial was registered at www.controlledtrials.com as ISRCTN49980913.