Rol de la cirugía bariátrica/metabólica en el manejo de la diabetes mellitus 2. Consenso SOCHED/SCCBM / Consensus statement of the Chilean endocrinological society on the role of bariatric surgery in type 2 diabetes

Diabetes Mellitus (DM) and obesity are a public health problem in Chile. Bariatric surgery is the most effective treatment alternative to achieve a significant and sustained weight reduction in patients with morbid obesity. The results of controlled clinical trials indicate that, compared to medical treatment, surgery for obese patients with DM2 allows a better control of blood glucose and cardiovascular risk factors, reduces the need for medications and increases the likelihood for remission. Consensus conferences and clinical practice guidelines support bariatric surgery as an option to treat DM2 in Class III Obesity (Body Mass Index (BMI) > 40) regardless of the glycemic control and the complexity of pharmacological treatment and in Class II Obesity (BMI 35-39,9) with inadequate glycemic control despite optimal pharmacological treatment and lifestyle. However, surgical indication for patients with DM2 and BMI between 30-34.9, the most prevalent sub-group, is only suggested. The Chilean Societies of Endocrinology and Diabetes and of Bariatric and Metabolic Surgery decided to generate a consensus regarding the importance of other factors related to DM2 that would allow a better selection of candidates for surgery, particularly when weight does not constitute an indication. Considering the national reality, we also need a statement regarding the selection and characteristics of the surgical procedure as well as the role of the diabetologist in the multidisciplinary team.

[Consensus statement of the Chilean endocrinological society on the role of bariatric surgery in type 2 diabetes]. / Rol de la cirugía bariátrica/metabólica en el manejo de la diabetes mellitus 2. Consenso SOCHED/SCCBM.

Diabetes Mellitus (DM) and obesity are a public health problem in Chile. Bariatric surgery is the most effective treatment alternative to achieve a significant and sustained weight reduction in patients with morbid obesity. The results of controlled clinical trials indicate that, compared to medical treatment, surgery for obese patients with DM2 allows a better control of blood glucose and cardiovascular risk factors, reduces the need for medications and increases the likelihood for remission. Consensus conferences and clinical practice guidelines support bariatric surgery as an option to treat DM2 in Class III Obesity (Body Mass Index (BMI) > 40) regardless of the glycemic control and the complexity of pharmacological treatment and in Class II Obesity (BMI 35-39,9) with inadequate glycemic control despite optimal pharmacological treatment and lifestyle. However, surgical indication for patients with DM2 and BMI between 30-34.9, the most prevalent sub-group, is only suggested. The Chilean Societies of Endocrinology and Diabetes and of Bariatric and Metabolic Surgery decided to generate a consensus regarding the importance of other factors related to DM2 that would allow a better selection of candidates for surgery, particularly when weight does not constitute an indication. Considering the national reality, we also need a statement regarding the selection and characteristics of the surgical procedure as well as the role of the diabetologist in the multidisciplinary team.

Safety and efficacy of the endoscopic duodenal-jejunal bypass liner prototype in severe or morbidly obese subjects implanted for up to 3 years.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that mimics the duodenal-jejunal exclusion component of the Roux-en-Y gastric bypass. Previous studies assessing the efficacy of the DJBL have shown 10-40% excess weight loss (%EWL) and improvements in obesity-associated comorbidities. The aim of this study was to evaluate the safety and efficacy of a new DJBL prototype over a 3-year period. METHODS: Morbidly obese subjects were enrolled in a single-arm, open-label, prospective trial. The subjects were offered the opportunity to continue with the trial annually and signed a new consent form. The primary endpoint was safety. The secondary endpoints were changes in weight and biochemical parameters from baseline. RESULTS: The DJBL was implanted endoscopically in 80 subjects (age: 35±10 years; 69% female; weight: 109±17 kg; BMI: 42±5.4 kg/m2). Seventy-two severe adverse events (AEs) were observed in 55 patients (68%), of which nine subjects required a prolonged hospital stay and three subjects required major interventions. Overall, 23 subjects (29%) underwent early device removal due to AEs. Additionally, 95% of the patients experienced mild AEs that mainly consisted of abdominal pain. The severe AEs included a liver abscess (3), upper GI bleeding (4), cholangitis (1), and acute pancreatitis (1) and mostly occurred after 12 months of follow-up. Two patients presented a short esophageal perforation during explantation. These perforations were successfully managed with endoscopic closure in one subject and medical treatment in the other subject. In the completer population at 52 weeks (71 patients), 104 weeks (40 patients), and 156 weeks (11 patients), the mean %EWL were 44 ± 16, 40 ± 22, and 39 ± 20, respectively (p < 0.001). CONCLUSION: This study shows significant and sustained weight loss after 3 years of treatment with the new DJBL. However, the high frequency and severity of AEs preclude the use of this prototype for periods longer than 1 year.

Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients.

Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies.

Bile acids synthesis decreases after laparoscopic sleeve gastrectomy.

BACKGROUND: Bariatric surgery is the most effective treatment alternative in morbid obesity. The mechanisms contributing to these benefits remain poorly understood. Bile acids (BAs) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure. Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy (SG). OBJECTIVES: The aim of this study was to evaluate the effect of SG on BA synthesis. SETTING: University Hospital. Santiago, Chile. METHODS: Obese patients were evaluated before and after SG (1, 3, 6, and 12 months). BA synthesis was evaluated through the serum marker, 7 α-hydroxy-4-cholesten-3-one (C4). Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with tandem mass spectrometry detection (HPLC-MS/MS). RESULTS: From June 2013 to January 2014, 19 patients (age 37.6±7.8 years; BMI 35.8±3.5 kg/m(2); 79% female) were included in this study. Mean weight loss at 1, 3, 6, and 12 months was 11.3, 17.5, 23.6, and 25.4 kg, respectively, equivalent to 11.8, 18.6, 24.8, and 26.9 of total body water percentage (%TBW) (P<.0001), respectively and 43.2, 68.2, 91, and 98.8 of percentage of excess weight loss (%EWL), respectively (P<.001). Serum C4 levels at baseline, 1, 3, 6, and 12 months were 23.4±21.1, 4.9±8.2, 8.7±12.1, 13.8±12.9, and 18.8±16.8 ng/mL (P<.0001), respectively. Fibroblast growth factor 19 (FGF19) levels at baseline, 1, 3, 6, and 12 months were 71±33.3, 130.5±66.2, 117.8±57.2, 134.6±91.7, and 124.3±85.9 pg/mL (P = .019), respectively. CONCLUSION: Serum levels of C4 decrease after SG, indicating a reduction in the synthesis of BA. FGF19 may play a role in decreasing BA synthesis. Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis.

[Totally laparoscopic gastrectomy for the treatment of gastric tumors]. / Gastrectomía totalmente laparoscópica por neoplasias gástricas: Experiencia en un centro público.

BACKGROUND: The laparoscopic approach for the treatment of gastric tumors has many advantages. AIM: To evaluate the results of a laparoscopic gastrectomy program developed in a public hospital. PATIENTS AND METHODS: Retrospective review of epidemiological, perioperative and follow-up data of patients who were treated with a laparoscopic gastrectomy due to gastric tumors between 2006 and 2013. A totally laparoscopic technique was used for all cases. Complications were evaluated according to the Clavien-Dindo classification. RESULTS: Fifty one patients, aged 65 (36-85) years, underwent a laparoscopic gastrectomy. In 22 patients a total gastrectomy was performed. Conversion rate to open surgery was 8%. Operative time was 330 (90-500) min and bleeding was 200 (20-500) ml. Median hospital stay was 7 (3-37) days. Postoperative morbidity was present in 17 (33%) patients, 3 (6%) patients had complications grade 3 or higher and one patient died (1.9%). Tumor pathology was adenocarcinoma in 39 patients. A complete resection was achieved in 97%. Twenty nine patients (74%) with gastric adenocarcinoma had early gastric cancer and 84% of patients were in stage one. Median lymph node count was 24. Median follow-up was 26 (1-91) months. There was no cancer related mortality among patients subjected to a curative resection. Overall survival for patients with adenocarcinoma was 92% at 3 years. CONCLUSIONS: This study supports the feasibility and safety of a laparoscopic gastrectomy program in a public hospital; with low morbidity, adequate lymph node dissection and long-term survival. This approach must be considered an option for selected patients with gastric cancer.

Gastrectomía totalmente laparoscópica por neoplasias gástricas: Experiencia en un centro público / Totally laparoscopic gastrectomy for the treatment of gastric tumors

Background: The laparoscopic approach for the treatment of gastric tumors has many advantages. Aim: To evaluate the results of a laparoscopic gastrectomy program developed in a public hospital. Patients and Methods: Retrospective review of epidemiological, perioperative and follow-up data of patients who were treated with a laparoscopic gastrectomy due to gastric tumors between 2006 and 2013. A totally laparoscopic technique was used for all cases. Complications were evaluated according to the Clavien-Dindo classification. Results: Fifty one patients, aged 65 (36-85) years, underwent a laparoscopic gastrectomy. In 22 patients a total gastrectomy was performed. Conversion rate to open surgery was 8%. Operative time was 330 (90-500) min and bleeding was 200 (20-500) ml. Median hospital stay was 7 (3-37) days. Postoperative morbidity was present in 17 (33%) patients, 3 (6%) patients had complications grade 3 or higher and one patient died (1.9%). Tumor pathology was adenocarcinoma in 39 patients. A complete resection was achieved in 97%. Twenty nine patients (74%) with gastric adenocarcinoma had early gastric cancer and 84% of patients were in stage one. Median lymph node count was 24. Median follow-up was 26 (1-91) months. There was no cancer related mortality among patients subjected to a curative resection. Overall survival for patients with adenocarcinoma was 92% at 3 years. Conclusions: This study supports the feasibility and safety of a laparoscopic gastrectomy program in a public hospital; with low morbidity, adequate lymph node dissection and long-term survival. This approach must be considered an option for selected patients with gastric cancer.

High frequency of internal hernias after Roux-en-Y gastric bypass.

BACKGROUND: Internal hernias (IH) after Roux-en-Y gastric bypass (RYGB) are a serious concern among surgeons and are often under-diagnosed due to heterogeneity of clinical manifestations. Our aim is to assess the frequency of IH after a RYGB in symptomatic and asymptomatic patients. METHODS: Retrospective analysis of our bariatric surgery unit's database between 2001 and 2013 is obtained. Patients are surgically explored after RYGB due to acute bowel obstruction (ABO), intermittent abdominal pain (IAP), or being asymptomatic (during an elective cholecystectomy) in whom anatomical presence of IH was established. Also, we compared patients with retrocolic and antecolic technique. Statistical analysis with non-parametric tests and chi-square are used. RESULTS: Of the patients, 3,656 submitted to RYGB during this period, 81.9% (2,993) by laparoscopy and 26.3% (963) with retrocolic technique. Of the patients, 130 (3.5%) were surgically explored due to ABO, 27 patients (0.7%) due to IAP, and 93 patients (2.5%) submitted to an elective cholecystectomy with exploration for IH. IH was present in 75% of the obstructed patients, and in 69%, it was the cause of obstruction. Patients with IAP showed 59% of IH, but only 15% have herniated bowel. In asymptomatic patients, 25% showed IH and none of them have herniated bowel. Retrocolic technique showed a higher risk of whole causes of ABO and IH than the antecolic technique, with a relative risk of 1.53 (1.07-2.17) and 1.62 (1.06-2.47), respectively. CONCLUSIONS: A high frequency of IH exists in all operated patients of this series. All members of the bariatric team should be aware of the symptoms related to IH and actively pursue it during follow-up.

Duodenal-jejunal bypass liner to treat type 2 diabetes mellitus in morbidly obese patients.

Endoscopic placement of the duodenal-jejunal bypass liner (DJBL) in morbidly obese patients induces significant weight loss. Additionally, early studies reported significant improvements in several parameters of glucose homeostasis in morbidly obese patients with T2DM. The observed glycemic control occurred soon after device placement, after a minimal weight loss, suggesting the activation of weight loss-independent anti-diabetic mechanisms of glucose normalization. This effect is associated with favorable changes in hormones involved in glucose level regulation. Recently, larger clinical studies, focused primarily on the effect of the DJBL on T2DM treatment, have corroborated initial observations not only in morbidly obese patients but in non-morbidly obese diabetic patients as well. In this article we review the evidence from preclinical animal and clinical human studies that support the efficacy of DJBL to treat T2DM in obese patients.

Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients.

INTRODUCTION: Endoscopic treatment with the duodenal-jejunal bypass liner (DJBL) leads to significant weight loss in obese patients. We sought to identify clinical factors associated with weight loss in obese patients treated with the DJBL for 1 year. METHODS: Subjects with morbid obesity were enrolled in a single-arm, open-label, prospective trial and implanted with the DJBL. Patient demographics along with baseline comorbidities, anthropometrics, and biochemical variables were selected for univariate and multivariate analysis. RESULTS: The DJBL was implanted in 79 subjects and 61 completed 12 months of follow-up. There were 18 early removals. Baseline mean age and body mass index (BMI) were 35.4 ± 9.7 years and 43 ± 5.6 kg/m(2), respectively. Forty-four (72 %) were women. This population included 22 subjects with type 2 diabetes (T2DM). Twelve months after treatment, patients had a mean excess body weight loss (%EBWL) of 46 ± 18 %. Univariate analysis identified that fasting glycemia (r (2) = -0.303, p < 0.013), insulin-resistance determined by HOMA-IR (r (2) = -0.457, p < 0.019), and glycated hemoglobin (HbA1c) (r (2) = -0.471, p < 0.013) were associated inversely with %EBWL at 1 year. In this cohort of patients, the multivariate analysis indicated that only baseline HbA1c levels were associated inversely with %EBWL after 1 year of treatment (ß adjusted coefficient -0.758, p < 0.016). Importantly, no differences at 1 year in %EBWL were observed between patients with or without T2DM (%EBWL T2D 46.7 ± 20 % vs. non-T2DM 46.8 ± 18.6 %, p = 0.988). CONCLUSIONS: This analysis indicates that higher baseline HbA1c levels are associated independently with diminished body weight loss in obese patients treated with the DJBL independent of their diabetic status. These results show that DJBL induces clinically significant weight loss in both T2DM and non-T2DM patients.

[Results of bariatric surgery. Experience over 18 years]. / Experiencia de 18 años de cirugía de obesidad en la Pontificia Universidad Católica de Chile.

BACKGROUND: Bariatric surgery is the gold-standard treatment for morbid obesity because it has low morbidity rates in high-volume centers and generates long term sustained weight loss. AIM: To describe our experience in bariatric surgery since the creation of our bariatric program in 1992. MATERIAL AND METHODS: Retrospective analysis of all patients subjected to bariatric surgery from 1992 to December 2010. Data was obtained from the electronic institutional registry. The Procedures per-formed were open and laparoscopic Roux-en-Y gastric bypass (BPGA and BPGL, respectively), laparoscopic adjustable gastric band (BGAL) and laparoscopic sleeve gastrectomy (GML). RESULTS: A total of 4943 procedures were performed, 768 (16%) BPGA, 2558 (52%) BPGL, 199 (4%) BGAL and 1418 (29%) GML. The number of procedures progressively increased, from 100 cases in 2000 to over 700 cases in 2008. Proportion of femóles and preoperative mean body mass Índex fluctuated between 69 and 79% and 35 and 43 kg/m², respectively, among the different procedures. Early and late complications fluctuated between Oto 1% (higher on BPGA) and 3 to 32.7% (higher on BGAL), respectively. The excess weight lost at five years was 76.1% in BPGA, 92.5% in BPGL and 53.7% in BGAL. The figure for GML at three years was 73.7%. CONCLUSIONS: The complication rates of this series of patients are similar to those reported in large series abroad. BPGL is still the most effective procedure; however GML is an attractive alternative for less obese patients.

Experiencia de 18 años de cirugía de obesidad en la Pontificia Universidad Católica de Chile / Results of bariatric surgery. Experience over 18 years

Background: Bariatric surgery is the gold-standard treatment for morbid obesity because it has low morbidity rates in high-volume centers and generates long term sustained weight loss. Aim: To describe our experience in bariatric surgery since the creation of our bariatric program in 1992. Material and Methods: Retrospective analysis of all patients subjected to bariatric surgery from 1992 to December 2010. Data was obtained from the electronic institutional registry. The Procedures per-formed were open and laparoscopic Roux-en-Ygastric bypass (BPGA and BPGL, respectively), laparoscopic adjustable gastric band (BGAL) and laparoscopic sleeve gastrectomy (GML). Results: A total of 4943 procedures were performed, 768 (16%) BPGA, 2558 (52%) BPGL, 199 (4%) BGAL and 1418 (29%) GML. The number of procedures progressively increased, from 100 cases in 2000 to over 700 cases in 2008. Proportion of femóles and preoperative mean body mass Índex fluctuated between 69 and 79% and 35 and 43 kg/m², respectively, among the different procedures. Early and late complications fluctuated between Oto 1% (higher on BPGA) and 3 to 32.7% (higher on BGAL), respectively. The excess weight lost atfiveyears was 76.1 % in BPGA, 92.5%o in BPGL and 53.7% in BGAL. The figure for GML at three years was 73.7%. Conclusions: The complication rates ofthis series of patients are similar to those reported in large series abroad. BPGL is still the most effective procedure; however GML is an attractive alternative for less obese patients.

2013 WSES guidelines for management of intra-abdominal infections.

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high.The 2013 update of the World Society of Emergency Surgery (WSES) guidelines for the management of intra-abdominal infections contains evidence-based recommendations for management of patients with intra-abdominal infections.

Weight loss and metabolic improvement in morbidly obese subjects implanted for 1 year with an endoscopic duodenal-jejunal bypass liner.

OBJECTIVE: To evaluate safety, weight loss, and cardiometabolic changes in obese subjects implanted with the duodenal-jejunal bypass liner (DJBL) for 1 year. BACKGROUND: The DJBL is an endoscopic implant that mimics the duodenal-jejunal bypass component of the Roux-en-Y gastric bypass. Previous reports have shown significant weight loss and improvement in type 2 diabetes for up to 6 months. METHODS: Morbidly obese subjects were enrolled in a single arm, open label, prospective trial and implanted with the DJBL. Primary endpoints included safety and weight change from baseline to week 52. Secondary endpoints included changes in waist circumference, blood pressure, lipids, glycemic control, and metabolic syndrome. RESULTS: The DJBL was implanted endoscopically in 39 of 42 subjects (age: 36 ± 10 years; 80% female; weight: 109 ± 18 kg; BMI: 43.7 ± 5.9 kg/m); 24 completed 52 weeks of follow-up. Three subjects could not be implanted due to short duodenal bulb. Implantation time was 24 ± 2 minutes. There were no procedure-related complications and there were 15 early endoscopic removals. In the 52-week completer population, total body weight change from baseline was -22.1 ± 2.1 kg (P < 0.0001) corresponding to 19.9 ± 1.8% of total body weight and 47.0 ± 4.4% excess of weight loss. There were also significant improvements in waist circumference, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, and fasting glucose. CONCLUSIONS: The DJBL is safe when implanted for 1 year, and results in significant weight loss and improvements in cardiometabolic risk factors. These results suggest that this device may be suitable for the treatment of morbid obesity and its related comorbidities. This study was registered at www.clinicaltrials.gov (NCT00985491).

Completely laparoscopic versus open gastrectomy for early and advanced gastric cancer: a matched cohort study.

INTRODUCTION: The application of laparoscopic gastric surgery has rapidly increased for the treatment of early gastric cancer. However, laparoscopic gastrectomy for advanced tumor remains controversial, particularly in terms of oncologic outcomes. This study was designed to compare 3-year survival of laparoscopic versus open curative gastrectomy in early and advanced gastric cancer. METHODS: This was a retrospective matched cohort study. We included patients between 2003 and 2010 with an R0 resection. A totally laparoscopic technique was used and D2 lymph node dissection was practiced routinely. We performed an intracorporeal hand-sewn esophagojejunostomy in all laparoscopic total gastrectomy cases. We matched all laparoscopic cases 1:1 with open cases according to TNM AJCC seventh edition. We used Mann-Whitney or t test and Chi-square test to compare both groups. Kaplan-Meier analysis with log-rank test was performed to compare survival. RESULTS: We included 31 open and 31 laparoscopic cases (mean age 63 ± 14 years; 66% males). Both groups were identical in type of gastrectomy (71% total and 29% subtotal). There were no statistical difference between laparoscopic and open groups in age, sex, N category, tumor location and size, histological differentiation, and T category (48% T1, 13% T2, 16% T3, and 23% T4 in both groups), with 48% early and 52% advanced tumors. The median number of resected lymph nodes was similar: 35 (23-53) for laparoscopic and 39 (23-45) for open cases (P = 0.81). The median follow-up was 50 months. The overall 3-year survival was 82% for laparoscopic surgery and 87% for the open surgery group (P = 0.56). There were no difference in 3-year survival for the laparoscopic versus the open surgery groups for advanced tumors (74 vs. 75%, P = 0.88), N+ tumors (73 vs. 73%, P = 0.99) and for the different AJCC stages (stage 1: 94 vs. 100%, stage 2: 89 vs. 82%, and stage 3: 50 vs. 50%, P = 0.32, 0.83, and 0.98 respectively). CONCLUSIONS: In this preliminary report, with 52% of advanced tumor, the 3-year overall and stage-by-stage survival was comparable for laparoscopic and open curative gastrectomy.

Overexpression of 11ß-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease.

BACKGROUND: The enzyme 11ß-hydroxysteroid-dehydrogenase type 1 (11ß-HSD1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11ß-HSD1 overexpression in visceral adipose tissue (VAT) in non-alcoholic fatty liver disease (NAFLD) assessing sequential changes of enzyme expression, in hepatic and adipose tissue, and the occurrence of portal hypercortisolism in obese mice. 11ß-HSD1 expression was also assessed in tissues from obese patients undergoing bariatric surgery. METHODS: Peripheral and portal corticosterone levels and liver histology were assessed in ob/ob mice at two time points (8-12 weeks of age). 11ß-HSD1 tissue expression was assessed in by RT-pcr in ob/ob mice and in 49 morbidly obese patients. RESULTS: Portal corticosterone serum levels were higher in obese mice with a 26% decrease between 8 and 12 weeks of age (controls: 78.3 ± 19.7 ng/ml, 8-week-old ob/ob: 167.5 ± 14.5 ng/ml and 12-week-old ob/ob: 124.3 ± 28 ng/ml, P < 0.05). No significant differences were found in peripheral corticosterone serum levels. Expression of 11ß-HSD1 was lower in the liver [-45% at 8 weeks and -35% at 12-weeks (P = 0.0001)] and highly overexpressed in VAT in obese mice, compared to controls (128-fold higher in 8-week-old ob/ob and 41-fold higher in 12-week-old ob/ob, P < 0.01). No significant differences were seen in the expression of 11ß-HSD1 in subcutaneous adipose tissue. In multivariate analysis, human 11ß-HSD1 expression in VAT (OR: 1.385 ± 1.010-1.910) was associated with NAFLD. CONCLUSION: Murine NAFLD is associated with portal hypercortisolism and11ß-HSD1 overexpression in VAT. In humans, 11ß-HSD1 VAT expression was associated with the presence of NAFLD. Thus, local corticosteroid production in VAT may contribute to NAFLD pathogenesis.

Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease.

BACKGROUND: The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. AIM: To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. MATERIAL AND METHODS: Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. RESULTS: BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p < 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). CONCLUSIONS: Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.

Safety and efficacy of Roux-en-Y gastric bypass to treat type 2 diabetes mellitus in non-severely obese patients.

The efficacy of Roux-en-Y gastric bypass (RYGB) to control type 2 diabetes mellitus (T2DM) has been demonstrated in morbidly obese patients. Surgical procedures primarily focused on T2DM control in patients with body mass index (BMI) < 35 kg/m(2) have shown to effectively induce remission of T2DM. However, only few reports have evaluated the safety and efficacy of RYGB in this group of patients. The aim of this study is to assess the safety and efficacy of RYGB in TD2M patients with BMI < 35 kg/m(2). All T2DM patients with BMI < 35 kg/m(2) and at least 12 months of follow-up who underwent laparoscopic RYGB were included. Safety of the procedure was evaluated according to mortality, need of reoperation/conversion, and complication rates. Metabolic parameters were evaluated at baseline and 6, 12, and 24 months after surgery. Thirty patients were included. Seventeen (56.6%) were women. Age, BMI, and duration of diabetes were 48 ± 9 years, 33.7 ± 1.2 kg/m(2), 4 ± 2.9 years, respectively. No mortality was observed. No conversion/reoperation was needed. Average length of stay was 3.2 ± 0.9 days. Early and late postoperative complications were observed in five (16.6%) and five (16.6%) patients, respectively. Twelve months after surgery, remission was observed in 25 of 30 patients (83.3%). After 2 years, remission was achieved in 13 of 20 patients (65%), and hemoglobin A1c decreased from 8.1 ± 1.8% to 5.9 ± 1.1% and homeostasis model assessment of insulin resistance from 5.7 ± 3.2 to 1.9 ± 0.8 after 12 months. RYGB is a safe and effective procedure to induce T2DM remission in otherwise not eligible patients for bariatric surgery. Evidence from prospective studies is needed to validate this approach.

Overexpression of hepatic 5α-reductase and 11ß-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients.

11-ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5ß-reductases. Our aim was to assess the expression of the reductases in the liver and of 11ß-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5α- and 5ß-reductases, 11ß-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthropometric and biochemical variables were analyzed. Forty-one patients were recruited (age, 41.8 ± 10.6 years; body mass index, 42.1 ± 6.6 kg/m(2); 71% women). The expression of hepatic 5α- and 5ß-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11ß-HSD1 expression (r = +0.61, P < .001 for 5α-reductase and r = +0.50, P < .001 for 5ß-reductase). Hepatic 5α-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11ß-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5α-reductase and VAT 11ß-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5α-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11ß-HSD1 to avoid systemic hypercortisolism.