Surgical Prevention of Weight Regain and Type 2 Diabetes Recurrence in 3 Different Bariatric Operations and Their Differential Long-Term Outcome: An 8-Year Prospective Observational Study.

Introduction: Comparative data on long-term outcomes of mechanistically different bariatric operations are scarce.

Methods: In this prospective, observational study, consecutive patients with severe obesity were studied using a predefined reoperation algorithm to determine long-term health outcomes after bariatric surgery (BS): adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD). All patients were assessed for mortality, postoperative weight loss, rate of reoperation, comorbidities, and quality of life (QoL) 8 years after surgery.

Reversal of Long-Term Weight Regain After Roux-en-Y Gastric Bypass Using Liraglutide or Surgical Revision. A Prospective Study.

Purpose: This study investigates whether pharmacotherapy with liraglutide is similarly effective in reversing weight regain more than 6 years after Roux-en-Y gastric bypass (RYGB) as revisional surgery aimed at restoring restriction.

Methods: Ninety-five consecutive patients (11 male, 84 female; mean BMI 45 ± 6 kg/m) undergoing RYGB 9 ± 4 years ago were treated for 24 months as follows: Patients, who gained less than 10% from weight NADIR, served as controls and were provided lifestyle counseling (DC, n = 30). The others were allowed to choose between three different treatment groups: daily s.

Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study.

Objective: Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance.

Research Design And Methods: Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation.

Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features.

Sim1 haploinsufficiency in mice induces hyperphagic obesity and developmental abnormalities of the brain. In humans, abnormalities in chromosome 6q16, a region that includes SIM1, were reported in obese children with a Prader-Willi-like syndrome; however, SIM1 involvement in obesity has never been conclusively demonstrated. Here, SIM1 was sequenced in 44 children with Prader-Willi-like syndrome features, 198 children with severe early-onset obesity, 568 morbidly obese adults, and 383 controls.

Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations.

We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index.

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human.

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference.

Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity.

Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity.

Prevalence of loss-of-function FTO mutations in lean and obese individuals.

Objective: Single nucleotide polymorphisms (SNPs) in intron 1 of fat mass- and obesity-associated gene (FTO) are strongly associated with human adiposity, whereas Fto(-/-) mice are lean and Fto(+/-) mice are resistant to diet-induced obesity. We aimed to determine whether FTO mutations are disproportionately represented in lean or obese humans and to use these mutations to understand structure-function relationships within FTO.

Research Design And Methods: We sequenced all coding exons of FTO in 1,433 severely obese and 1,433 lean individuals.

The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects.

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.

Successful multi-intervention treatment of severe obesity: a 7-year prospective study with 96% follow-up.

Background: No long-term, high participation study of the outcome of bariatric surgery has examined how a multi-intervention approach to the treatment of severe obesity can achieve and sustain weight loss after an initial bariatric procedure.

Methods: We employed a multi-intervention treatment that combines adjustable gastric banding with intensive follow-up to support patient life-style change and use of an algorithm allowing reoperation-to bypass, if necessary-in the event of complications. Four hundred four severely obese patients with an average BMI = 42.

Common nonsynonymous variants in PCSK1 confer risk of obesity.

Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.

Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees.

Objective: Melanocortin-4 receptor (MC4R) deficiency is the most frequent genetic cause of obesity. However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown.

Research Design And Methods: We determined the MC4R sequence in 2,257 obese individuals and 2,677 nonobese control subjects of European origin and established the likely functional impact of all variants detected.

The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.

Background: Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects.

Methods: We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI.

Results: Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.

Severe recurrent hypoglycemia after gastric bypass surgery.

Background: Bariatric surgery is, at present, the most effective method to achieve major, long-term weight loss in severely obese patients. Recently, severe recurrent symptomatic hyperinsulinemic hypoglycemia was described as a consequence of gastric bypass surgery (GBS) in a small series of patients with severe obesity. Pancreatic nesidioblastosis, a hyperplasia of islet cells, was postulated to be the cause, and subtotal or total pancreatectomy was the suggested treatment.

Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations.

The therapeutic effects of cannabinoid receptor blockade on obesity-associated phenotypes underline the importance of the endocannabinoid pathway on the energy balance. Using a staged-approach, we examined the contribution of the endocannabinoid receptor 1 gene (CNR1) on obesity and body mass index (BMI) in the European population. With the input of CNR1 exons and 3' and 5' regions sequencing and HapMap database, we selected and genotyped 26 tagging single-nucleotide polymorphisms (SNPs) in 1932 obese cases and 1173 non-obese controls of French European origin.

Bowel habits after bariatric surgery.

Background: Disordered bowel habits might influence quality of life after bariatric surgery. Different types of bariatric operations-gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD)-might alter bowel habits as a consequence of the surgical procedure used. Whether change in bowel habits affects quality of life after AGB, RYGB, or BPD differently is unknown.

Effects of TCF7L2 polymorphisms on obesity in European populations.

The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele was previously associated with type 2 diabetes (T2D) and decreased BMI whereas haplotypes carrying the rs7903146 C and rs10885406 A alleles (HapA) were associated with increased BMI. The functional relevance of TCF7L2 polymorphisms and their effects on T2D and obesity remained to be further investigated. In white European populations, we found that the rs7903146 T allele was more associated with T2D in 3,547 non-obese individuals (odds ratio (OR) = 1.

Interdisciplinary European guidelines on surgery of severe obesity.

In 2005, for the first time in European history, an extraordinary expert panel named BSCG (Bariatric Scientific Collaborative Group), was appointed through joint effort of the major European scientific societies which are active in the field of obesity management. Societies that constituted this panel were: IFSO - International Federation for the Surgery of Obesity, IFSO-EC - International Federation for the Surgery of Obesity - European Chapter, EASO - European Association for Study of Obesity, ECOG - European Childhood Obesity Group, together with the IOTF (International Obesity Task Force) which was represented during the completion process by its representative. The BSCG was composed not only of the top officers representing the respective scientific societies (four acting presidents, two past presidents, one honorary president, two executive directors), but was balanced with the presence of many other key opinion leaders in the field of obesity.

Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene.

The melanocortin-4 receptor (MC4R) gene pathogenic mutations are the most prevalent forms of monogenic obesity, responsible for approximately 2% of obesity cases, but its role in common obesity is still elusive. We analyzed the contribution of non-synonymous mutations V103I (rs2229616, c.307G > A) and I251L (no rs, c.