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Background: Patients undergoing bariatric surgery have a high incidence of non-alcoholic fatty liver disease (NAFLD). However, the effect of NAFLD or non-alcoholic steatohepatitis (NASH) on the weight loss and resolution of obesity-related disorders is a matter of debate., Methods: In this study, we compare the long-term outcomes after bariatric with the presence of NAFLD in the liver biopsy at the time of surgery., Results: The follow-up was available for 226 out of 288 patients. The mean follow-up time was 24.9 (± 13.6) months. The baseline histology showed that 112 patients (38.9%) had no NASH, 70 (24.3%) were borderline, and 106 (36.8%) had NASH. At follow-up, the mean BMI dropped from (52 ± 10.2) to (36.6 ± 8) kg/m 2 . Excess weight loss (EWL) was similar in all NAFLD groups. Type 2 diabetes mellitus dropped from 35.7 to 11.4%, hypertension from 65.6 to 36.7%, hyperlipidemia from 62.3 to 33%, and obstructive sleep apnea from 37.5 to 14.9%. Only hyperlipidemia was significantly associated with NASH compared to the groups with no NASH or borderline NASH (p value = 0.002 and p value = 0.04, respectively) during the first two years of follow-up., Conclusion: The beneficial effects of bariatric surgery are evident across all patients with NAFLD. Patients with NASH have comparable outcomes regarding weight loss and resolution of obesity-related comorbidities., (© 2023. The Author(s).)

De novo lipogenesis (DNL) in visceral adipose tissue (VAT) is associated with systemic insulin sensitivity. DNL in VAT is regulated through ChREBP activity and glucose uptake through Glut4 (encoded by Slc2a4 ). Slc2a4 expression, ChREBP activity, and DNL are decreased in obesity, the underlying cause however remains unidentified. We hypothesize that increased DNA methylation in an enhancer region of Slc2a4 decreases Slc2a4 expression in obesity and insulin resistance. We found that SLC2A4 expression in VAT of morbidly obese subjects with high HbA1c (>6.5%, n = 35) is decreased, whereas DNA methylation is concomitantly increased compared to morbidly obese subjects with low HbA1c (≤6.5%, n = 65). In diet-induced obese (DIO) mice, DNA methylation of Slc2a4 persistently increases with the onset of obesity and insulin resistance, while gene expression progressively decreases. The regulatory impact of DNA methylation in the investigated enhancer region on SLC2A4 gene expression was validated with a reporter gene assay. Additionally, treatment of 3T3 pre-adipocytes with palmitate/oleate during differentiation decreased DNA methylation and increased Slc2a4 expression. These findings highlight a potential regulation of Slc2a4 by DNA methylation in VAT, which is induced by fatty acids and may play a role in the progression of obesity and insulin resistance in humans.

Background: Bariatric-metabolic surgery (BS) decreases the grade of steatosis, hepatic inflammation, and fibrosis in patients with severe obesity and non-alcoholic fatty liver disease (NAFLD). Mechanisms include substantial weight loss, but also simultaneous effects on glucose homeostasis. Therefore, we aimed to investigate the association between NAFLD and remission of type 2 diabetes (T2D) up to 8 years following different types of BS., Methods: In a retrospective cohort study including 107 patients with obesity and T2D at baseline, the association between biopsy-proven NAFLD defined as steatosis in > 5% of hepatocytes at the time of surgery and T2D remission up to 8 years following different surgical procedures was investigated. Univariate regression analysis was used to examine the association between NAFLD and remission of T2D., Results: Long-term remission of T2D was present in 56% of patients (n = 60). The presence of low-grade liver steatosis (grade 1) was associated with remission of T2D. Patients with a liver steatosis score ≥ 2 showed higher HbA1c levels at baseline. There were no significant differences in preoperative presence of lobular inflammation, hepatocyte ballooning, or fibrosis between patients who achieved T2D remission compared with those with no remission. Type of surgery did not affect remission of T2D., Conclusion: Our results suggest that the presence of low-grade liver steatosis is associated with remission of T2D following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Therefore, BS should be considered at an early NAFLD stage in patients with T2D., (© 2022. The Author(s).)

Background: Bariatric surgery (BS) was shown to promote a decline in thyroid-stimulating hormone (TSH) in euthyroid patients with severe obesity in the short-term. Aim of the present study was to assess the effect of weight loss on thyroid function in euthyroid patients in the long-term following different bariatric procedures., Methods: In a retrospective cohort study including 135 patients at baseline, thyroid function was assessed at six time points up to 8 years after surgery. Patients were stratified by TSH levels at baseline and divided into two groups to compare the change in TSH at long-time. We used log-linear regression to assess the relation between thyroid hormones and TSH and linear regression analyses to identify variables that were thought to determine TSH and fT3/fT4-ratio as well as their change long-term., Results: Over a mean follow-up of 8 years, TSH and fT3/fT4-ratio declined (both p < 0.001). Patients with high-normal TSH showed a greater decline in TSH than those with normal TSH compared to baseline. Thyroid hormones and TSH displayed a negative log-linear correlation at long-term follow-up. Change in TSH at long-time showed a negative correlation with TSH at baseline (B = -0.55; p < 0.001). With regard to type of surgery, there were no significant differences in TSH., Conclusion: BS promotes a decline of TSH in euthyroid patients up to 8 years after intervention despite weight regain. The greatest change in TSH was seen among patients with high-normal baseline-TSH. Results of log-linear regression suggest recovery of the pituitary-thyroid axis. Type of surgery did not affect the change in TSH levels over time., (© 2022. The Author(s).)

Purpose: Venous thromboembolic events (VTEs) are common complications after bariatric surgery, and enoxaparin is commonly used to prevent VTEs. The risk for VTEs is sex-specific. Whether enoxaparin application results in similar anti-factor Xa activities (aFXa) in males and females with obesity remains to be determined. We investigated whether our dosage regimen of enoxaparin resulted in similar serum aFXa levels in female and male patients undergoing bariatric surgery., Materials and Methods: We administered enoxaparin twice daily in patients undergoing bariatric surgery. Patients with a body mass index (BMI) > 60 kg/m 2 (n = 11) received 60 mg enoxaparin (group 2), and patients with lower BMI (n = 86) received 40 mg per dose (group 1). Peak aFXa levels were measured 3 days after surgery. The primary outcome was the aFXa level. As a secondary outcome, we detected VTEs and major bleeding events and explored the possible influencing factors of aFXa., Results: Women had higher aFXa than men, but after matching for anthropometric values, the two groups were similar (females: 0.17 ± 0.08 U/ml; males: 0.18 ± 0.08 U/ml). Linear regression revealed a moderate relationship between weight and aFXa levels. The 3-month follow-up was attended by 94.9%, at which one patient had pulmonary embolism., Conclusion: Individual enoxaparin dosage regimens for men and women do not seem to be required. Weight-based dosing regimen seems to be a more reasonable choice., (© 2022. The Author(s).)

Background: Low socioeconomic status (SES) is associated with an increased prevalence of obesity. It is unknown whether SES influences the outcome after bariatric surgery in Germany. Therefore, the aim of our study was to investigate whether the SES is linked with an inferior outcome after bariatric surgery., Methods: We included all patients who underwent bariatric surgery in our university hospital from 2012-2014. Net income was estimated by matching the zip codes of patient residency with the region-specific purchasing power index. We analyzed the relationship between SES, weight loss and remission of comorbidities., Results: We included 559 patients in this study and detected a mean 5-year percentage excess weight loss (%EWL) of 52.3%. We detected a significantly lower initial body mass index (BMI) and weight in patients with a higher income. One year after surgery, we did not find a significant difference. Further analysis revealed that only women with a higher income had a significantly lower BMI and weight 3 and 5 years after surgery., Conclusions: Bariatric surgery is beneficial for all patients regardless of income. Furthermore, we demonstrated that women with high SES have a better outcome after bariatric surgery., (© 2021. The Author(s).)

Background: Non-invasive scores, such as the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), are increasingly used for liver fibrosis assessment in patients with NAFLD. The aim of this study was to assess the applicability and reliability of non-invasive fibrosis scores in NAFLD patients with and without morbid obesity., Methods: Three hundred sixty-eight patients with biopsy-proven NAFLD identified between January 2012 and December 2015 were studied; 225 with morbid obesity (biopsy obtained during bariatric surgery) and 143 patients without (termed as "conventional")., Results: Median age was 47 years, 57% were female. Median body mass index (BMI) was 42.9 kg/m 2 with significant differences between our conventional and morbidly obese patients (BMI 29.0 vs. 50.8 kg/m 2 , p < 0.001). Overall, 42% displayed mild/moderate and 16% advanced liver fibrosis (stage III/IV). All tested scores were significantly linked to fibrosis stage (p < 0.001 for all). FIB-4 (AUROC 0.904), APRI (AUROC 0.848), and NFS (AUROC 0.750) were identified as potent predictors of advanced fibrosis, although NFS overestimated fibrosis stage in morbid obesity. Limiting BMI to a maximum of 40 kg/m 2 improved NFS' overall performance (AUROC 0.838). FIB-4 > 1.0 indicated high probability of advanced fibrosis (OR = 29.1). FIB-4 predicted advanced fibrosis independently from age, sex, BMI, and presence of morbid obesity., Conclusions: Our data suggest that FIB-4 score is an accurate predictor of advanced fibrosis in NAFLD throughout all BMI stages. Without adjustment, NFS tends to overestimate fibrosis in morbidly obese NAFLD patients. This problem may be solved by implementation of an upper BMI limit (for NFS) or adjustment of diagnostic thresholds., (© 2021. The Author(s).)

Objective: The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN ( fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits., Subjects and Methods: Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing., Results: FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic ( SCD , ELOVL6 ) or lipolytic genes ( ADRB3 , PNPLA2 ) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = - 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005)., Conclusions: Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Bariatric surgery (BS) was shown to improve inflammatory markers in previous short-term follow-up studies. The aim of the present study was to assess the long-term effects of BS on chronic low-grade inflammation markers related to severe obesity. Moreover, the meaning of the type of BS procedure as well as the remission of type 2 diabetes (T2D) for inflammatory status up to 4 years after BS was analyzed., Materials and Methods: In a retrospective cohort study including 163 patients at baseline, inflammatory and metabolic parameters were assessed at 4 time points: before surgery (baseline), 6 months after surgery (visit 1), 2 years after surgery (visit 2), and 4 years after surgery (visit 3). Univariate regression analysis was used to identify variables that were thought to determine change in inflammatory parameters., Results: CRP, hs-CRP, leucocytes, and ferritin significantly declined in the mid- and long-term according to the U-shaped curve of weight loss (p<0.001). Change in body mass index (BMI) at long-time follow-up showed a significant linear effect on change in leucocytes (B=0.082; p<0.001) and change in hs-CRP (B=0.03; p<0.05). There was a strong, positive correlation between T2D and hs-CRP at visit 2 (r s =0.195; p<0.05) and visit 3 (r s =0.36; p=0.001). With regard to type of surgery and gender, there were no significant differences in inflammatory parameters., Conclusion: BS is able to reduce obesity-related chronic low-grade inflammation up to 4 years after surgical intervention. The improvement in metaflammation is related to the change in BMI and remission of T2D in the long-term.

Purpose: This study aims to assess the long-term renal effects of bariatric surgery (BS) in severely obese patients over a follow-up period of up to 11 years., Materials and Methods: In a retrospective cohort study including 102 patients, patients were stratified by eGFR at baseline and divided into three groups: (1) reduced, (2) normal, and (3) increased filtration rate. Adjustments for age- and sex-related decline in eGFR were performed. We used uni- and multivariate regression analysis to identify variables that were thought to determine change in eGFR., Results: Over a median follow-up of 8.5 years (interquartile range 2.7), eGFR declined from 96.1 ± 20.7 to 84.9 ± 21.0 ml/min (p < 0.001). Among patients with (1), eGFR remained stable (69.1 ± 19.3 ml/min). Among patients with (2), eGFR declined from 99.7 ± 13.3 ml/min to 88.7 ± 19.4 ml/min (p < 0.001). Among patients with (3), eGFR decreased to normal levels (94.2 ± 17.7 ml/min, p < 0.001). Age- and sex-adjusted eGFR increased (6.4 ± 14.4 ml/min; p < 0.05) among patients with reduced filtration rate. Among patients with normal filtration rate, adjusted eGFR remained stable during follow-up (-1.3 ± 15.2 ml/min; n.s.). Among patients with increased filtration rate, adjusted eGFR decreased and remained within the normal range (-13.2 ± 12.2 ml/min; p < 0.001). Change in eGFR showed a negative correlation with eGFR at baseline (B = -0.31; p < 0.001), change in LDL-cholesterol (B = -0.09; p < 0.05), and a negative correlation with treatment requiring hypertension (B = -9.36; p = 0.001)., Conclusion: BS is protective against renal function decline in severely obese patients in the long term.

Background: Prevalence of obesity is increasing with a pandemic magnitude worldwide. Incidence of super-super-obesity (> 60 kg/m 2 ) is expanding by the same means. While bariatric surgery is the only approach with proven long-term results, surgical outcome in super-super-obesity is still discussed controversially., Objective: This retrospective study examined bariatric surgery patients' short-term outcome in relation to their degree of obesity., Setting: Data collection was performed in a German university medical center between March 2010 and November 2013., Methods: This study analyzes a cohort of 715 patients in a single institution. Patients were subdivided into three groups, obese (≤ 49.9 kg/m 2 ), super-obese (≥ 50 kg/m 2 ), and super-super-obese (≥ 60 kg/m 2 ), and evaluated regarding perioperative outcome., Results: Three hundred eighty-one patients were included into obese (O); 225 patients, into super-obese (SO); and 109 patients, into super-super-obese (SSO) cohort. There were no significant differences regarding patient characteristics including quantity of comorbidities and perioperative outcome. BMI was significantly lower in patients with complications, compared to patients without complications (p < 0.05), whereas patients' age was significantly higher (p < 0.05) in complication cohort. One SSO patient died of a septic multiorgan failure. Thus, the 30-day overall mortality was 0.14%. The BMI showed an inverse correlation to the patients' age at surgery (p < 0.05)., Conclusion: Super-super-obesity should not be considered as a limiting factor for bariatric surgery outcome; however, the patients' age, surgeries prior to the bariatric procedure, and comorbidities must be considered prior to bariatric surgical treatment.

Background: Upper gastrointestinal pathologies are common in bariatric patients. Preoperative esophagogastroduodenal endoscopy (EGD) should detect and treat pathologies that might alter the type of bariatric surgery. However, clinical consequences of these findings are often insignificant. The aim of this study was to assess the influence of preoperative endoscopy in our cohort and its clinical consequences., Methods: We conducted a retrospective analysis of endoscopic findings in patients under evaluation for bariatric surgery. Endoscopic findings were compared to preoperative risk factors as well as postoperative complications, and its clinical consequences were analyzed., Results: Data was available for 801 patients. Abnormal endoscopic findings were found in 65.7% of all patients. The most common conditions were gastritis (32.1%) and gastroesophageal reflux (24.8%). Malignancies were observed in 0.5% of all patients. We observed early-stage adenocarcinoma of the esophagus in two patients through our routine preoperative evaluation. Helicobacter pylori infections were detected in preoperative biopsies in only 3.7% of all patients. Patients who reported reflux symptoms had a higher rate of pathological EGDs (74.2 vs. 64.9%, p .019). We did not find any other risk factors for a pathological endoscopy. The postoperative complication rate was 11.2%. Leakage rate was 1.1%. Mortality rate was 0.4%. We did not find any correlation between the incidence of postoperative complications and preoperative endoscopic findings., Conclusions: Relevant findings in routine preoperative endoscopy are rare but have significant influence on decision-making in bariatric patients and should be assessed as a necessary diagnostic tool.

Objectives: The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients and evaluate the influence on perioperative complications., Background: Patients undergoing bariatric surgery have a high incidence of non-alcoholic steatohepatitis (NASH). Upcoming data indicates that liver disease has a significant effect on perioperative complications. However, the influence of NAFLD/NASH on perioperative outcome in bariatric patients is still controversial., Methods: We identified a total of 302 patients with concomitant liver biopsies, while performing either laparoscopic Roux-Y gastric bypass or sleeve gastrectomy. Liver biopsy was performed in case of abnormal liver appearance at time of bariatric surgery. Histological results were compared to perioperative complication rate., Results: NAFLD is common in our patient cohort. Abnormal findings in liver histology were found in 82.3 % of our patients. Liver cirrhosis was newly diagnosed in 12 patients (4 %). There were no complications due to liver biopsy. The mortality rate was 0.3 %, leakage rate was 1 %, and postoperative bleeding occurred in 3.3 %. Pulmonary complications were observed in 1.7 % and cardiovascular complications in 1.3 %. One patient developed portal vein thrombosis and one patient acute pancreatitis; both were treated conservatively. No patient had postoperative liver failure. We found no association between histological findings and perioperative outcomes., Conclusions: The prevalence of NAFLD among morbidly obese surgical patients was high, although this condition was not associated with increased risk for postoperative complications. Because of unexpected findings in intraoperative liver biopsies, the routine indication of liver biopsies in patients at high risk for liver disease should be discussed.

Background: Bariatric surgery has increased in numbers, but the treatment of morbid obesity in Germany still needs improvement. The new interdisciplinary S3-guideline provides information on the appropriate indications, procedures, techniques, and follow-up care., Methods: Systematic review of the literature, classification of the evidence, graded recommendations, and interdisciplinary consensus-building., Results: Bariatric surgery is a component of the multimodal treatment of obesity, which consists of multidisciplinary evaluation and diagnosis, conservative and surgical treatments, and lifelong follow-up care. The current guideline extends the BMI-based spectrum of indications that was previously proposed (BMI greater than 40 kg/m(2), or greater than 35 kg/m(2)with secondary diseases) by eliminating age limits, as well as most of the contraindications. A prerequisite for surgery is that a structured, conservative weight-loss program has failed or is considered to be futile. Type 2 diabetes is now considered an independent indication under clinical study conditions for patients whose BMI is less than 35 kg/m(2) (metabolic surgery). The standard laparoscopic techniques are gastric banding, gastric bypass, sleeve gastrectomy, and biliopancreatic diversion. The choice of procedure is based on knowledge of the results, long-term effects, complications, and individual circumstances. Structured lifelong follow-up should be provided and should, in particular, prevent metabolic deficiencies., Conclusion: The guideline contains recommendations based on the scientific evidence and on a consensus of experts from multiple disciplines about the indications for bariatric surgery, the choice of procedure, techniques, and follow-up care. It should be broadly implemented to improve patient care in this field.

Background: Previous studies have shown that a preoperative weight loss is associated with better long-term outcome, fewer complications, and less time in the operating room in bariatric patients. However, preoperative weight loss is hard to achieve in many patients., Methods: We, therefore, conducted a study in which 20 bariatric patients received 15 mg of the weight loss medication sibutramine prior to laparoscopic Roux-en-Y gastric bypass (RYGBP) while patients in the control group did not. It was our interest to find out if these patients had a benefit compared to a control group who did not receive medication., Results: Whereas patients in the sibutramine group lost 4.8 kg within 6 weeks, patients in the control group gained 7.0 kg. Along with the change in weight, the size of the left liver lobe decreased in the sibutramine-treated patients and increased in the control group. Glutamic pyruvic transaminase as a parameter of liver function improved with reduction of liver size. Finally, time in the operating room was shorter for patients with preoperative weight loss due to sibutramine intake., Conclusions: Medical therapy with sibutramine in preparation for bariatric surgery can improve the health status of patients and lead to a reduction of liver size and operating time. It should be considered as an alternative or addition to dietary therapy or gastric balloon treatment in the preparation of patients expecting a RYGBP.