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. Results: Between 1996 and 2008, 2364 Swiss patients, with a mean body mass index of 43 ± 7 kg/m2 (mean ± SD) underwent AGB (n = 1404), RYGB (n = 790), or BPD (n = 170). Two thousand two hundred twenty-eight (94%) were followed for 8 years after BS. Eight-year mortality of the whole study group was 34.3 per 104 person-years. Percent excessive weight loss at 8 years was 56.7 ± 1.4% (95% confidence interval) in AGB, 62.5 ± 2.4% in RYGB and 64.8+-3.0% in BPD. The rate of major reoperation was highest in AGB and significantly lower in RYGB and BPD (63.4 vs 54.3 vs 47.2 per 103 person-years, P < 0.001). Remission of comorbidities was observed across all 3 groups, with key improvement (P < 0.01) in esophagitis in the RYGB group, and type 2 diabetes (T2D) (>60%) in procedures involving duodenal exclusion. Total improvement in QoL was similar between the 3 types of operations but was strongly correlated with weight loss preservation (P < 0.001). Conclusions: BS, at the expense of a high reoperation rate but low procedural mortality, considerably improves the QoL and results in sustained remission of comorbidities, especially T2D using a predefined reoperation algorithm developed to prevent weight regain and operation-specific complications.

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/m2) 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.c. administration of liraglutide (LG, n = 34); endosurgery using Apollo's Overstitch System™ (ES, n = 15), or implantation of a Fobi-ring with pouch resizing (FP, n = 16). RESULTS: Controls kept their weight stable during 24 months of study (- 0.1 ± 1.7 kg/m2). Weight loss was 4.8 ± 2.9 kg/m2 for LG and 5.5 ± 2.9 kg/m2 for FP, both losing more than 85% of regained weight from weight NADIR (p < 0.001). In contrast, weight loss in ES was 1.0 ± 0.9 kg/m2 (i.e., 20% of regained weight). Thirty-seven percent of FP experienced serious complications (p < 0.05) in contrast to the other groups. An improved prevalence of hypertension and dyslipidemia was observed in LG and FP (p < 0.02) 24 months after intervention. CONCLUSIONS: Weight regain during more than 6 years after RYGB can be safely and effectively reversed with liraglutide. Compared with revisional surgery, pharmacotherapy with liraglutide was low risk and resulted in an important improvement in hypertension and dyslipidemia. Therefore, daily subcutaneous injections of liraglutide are a valid option to treat weight regain after RYGB.

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. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years. RESULTS: At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates. CONCLUSIONS: Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.

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. We identified 4 rare variants (p.I128T, p.Q152E, p.R581G, and p.T714A) in 4 children with Prader-Willi-like syndrome features (including severe obesity) and 4 other rare variants (p.T46R, p.E62K, p.H323Y, and p.D740H) in 7 morbidly obese adults. By assessing the carriers' relatives, we found a significant contribution of SIM1 rare variants to intra-family risk for obesity. We then assessed functional effects of the 8 substitutions on SIM1 transcriptional activities in stable cell lines using luciferase gene reporter assays. Three mutations showed strong loss-of-function effects (p.T46R, p.H323Y, and p.T714A) and were associated with high intra-family risk for obesity, while the variants with mild or no effects on SIM1 activity were not associated with obesity within families. Our genetic and functional studies demonstrate a firm link between SIM1 loss of function and severe obesity associated with, or independent of, Prader-Willi-like features.

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. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (ß = 0.180 [0.022-0.339], P value = 0.0258 and ß = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (ß = 0.151 [-0.006 to 0.309], P value = 0.0591 and ß = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.

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. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.

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. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.

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. We studied the enzymatic activity of selected nonsynonymous variants. RESULTS: We identified 33 heterozygous nonsynonymous variants in lean (2.3%) and 35 in obese (2.4%) individuals, with 8 mutations unique to the obese and 11 unique to the lean. Two novel mutations replace absolutely conserved residues: R322Q in the catalytic domain and R96H in the predicted substrate recognition lid. R322Q was unable to catalyze the conversion of 2-oxoglutarate to succinate in the presence or absence of 3-methylthymidine. R96H retained some basal activity, which was not enhanced by 3-methylthymidine. However, both were found in lean and obese individuals. CONCLUSIONS: Heterozygous, loss-of-function mutations in FTO exist but are found in both lean and obese subjects. Although intron 1 SNPs are unequivocally associated with obesity in multiple populations and murine studies strongly suggest that FTO has a role in energy balance, it appears that loss of one functional copy of FTO in humans is compatible with being either lean or obese. Functional analyses of FTO mutations have given novel insights into structure-function relationships in this enzyme.

Genetic variant in HK1 is associated with a proanemic state and A1C but not other glycemic control-related traits.

OBJECTIVE: A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice. RESEARCH DESIGN AND METHODS: The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control-related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients. RESULTS: Our study confirms a strong association between the rs7072268-T allele and increased A1C (beta = 0.029%; P = 2.22 x 10(-7)). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT-related parameters, n = 18,694). In contrast, rs7072268-T allele decreases hemoglobin levels (n = 13,416; beta = -0.054 g/dl; P = 3.74 x 10(-6)) and hematocrit (n = 11,492; beta = -0.13%; P = 2.26 x 10(-4)), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018). CONCLUSIONS: HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia is a frequent complication of the diabetes state.

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) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.

Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.

We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 x 10(-7)), near MAF (encoding the transcription factor c-MAF, P = 3.8 x 10(-13)) and near PTER (phosphotriesterase-related gene, P = 2.1 x 10(-7)).

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 = 42.6 at the outset had initial AGB surgery and were followed with a high rate of face-to-face consultations for 7 years. Seventy-five percent of the patients retained a gastric band throughout the study. Weight loss, complications, and comorbidities were studied, and quality of life was assessed using Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: Three hundred eighty-eight (96%) patients completed the 7-year follow-up. Average BMI reduction at 5 years was 28% and remained stable through year 7, at which the mean excess weight loss was 61%. The preoperative prevalence of metabolic syndrome, 59.7%, decreased to 13.3% at 7 years and was abolished for patients with more than 40% loss of initial BMI. Similar changes were seen for all components of metabolic syndrome. More than 60% of patients had a "good" or higher BAROS score; 10.1% were considered failures. Patients converted to gastric bypass, and those retaining gastric bands throughout the study had very similar outcomes. CONCLUSIONS: Long-term, multi-intervention treatment of severe obesity can achieve and preserve weight loss and thus improved quality of life and sustained reduction or disappearance of all components of metabolic syndrome, for a high proportion of severely obese patients with preoperative BMI between 35 and 55.

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 = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.

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. We then included relatives of probands carriers and studied 25 pedigrees, including 97 carriers and 94 noncarriers from three generations. RESULTS: Of the MC4R nonsynonymous mutations found in obese subjects, 68% resulted in a loss of function in vitro. They were found in 1.72% of obese versus 0.15% of nonobesed subjects (P = 6.9 x 10(-10)). Among the families, abnormal eating behavior was more frequent in both MC4R-deficient children and adults than in noncarriers. Although BMI was inversely associated with educational status in noncarrier adults, no such relationship was seen in MC4R mutation carriers. We observed a generational effect, with a penetrance of 40% in MC4R-deficient adults aged >52 years, 60% in 18- to 52-year-old adults, and 79% in children. The longitudinal study of adult carriers showed an increasing age-dependent penetrance (37% at 20 years versus 60% at >40 years). CONCLUSIONS: We have established a robust estimate of age-related penetrance for MC4R deficiency and demonstrated a generational effect on penetrance, which may relate to the development of an "obesogenic" environment. It remains to be seen whether appropriate manipulation of environmental factors may contribute to preventing the development of obesity even in those strongly genetically predisposed to it.

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) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 x 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 x 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 x 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals. CONCLUSION: Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.

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. Variants that showed significant associations (P < 0.05) with obesity after correction for multiple testing were further tested in two additional European cohorts including 2645 individuals. For the identification of the potential causal variant(s), we further genotyped SNPs in high linkage disequilibrium (LD) with the obesity-associated variants. Of the 25 successfully genotyped CNR1 SNPs, 12 showed nominal evidence of association with childhood obesity, class I and II and/or class III adult obesity (1.16 < OR < 1.40, 0.00003 < P < 0.04). Intronic SNPs rs806381 and rs2023239, which resisted correction for multiple testing were further associated with higher BMI in both Swiss obese subjects and Danish individuals. The genotyping of all know variants in partial LD (r(2) > 0.5) with these two SNPs in the initial case-control study, identified two better associated SNPs (rs6454674 and rs10485170). Our study of 5750 subjects shows that CNR1 variations increase the risk for obesity and modulate BMI in our European population. As CB1 is a drug target for obesity, a pharmacogenetic analysis of the endocannabinoid blockade obesity treatment may be of interest to identify best responders.

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. METHODS: We observed that severe, disabling hypoglycemia after GBS occurred only in patients with loss of restriction. Whether restoration of gastric restriction might treat severe, recurrent hypoglycemia after GBS is unknown. RESULTS: Therefore, gastric restriction was restored by surgical placement of a silastic ring (n = 8, first two patients with additional distal pancreatectomy) or an adjustable gastric band (n = 4) around the pouch in 12 consecutive patients presenting with severe hypoglycemia (blood glucose below 2.2 mM). At follow-up after restoration of gastric restriction (median follow-up 7 months, range 5 to 19 months), 11 patients demonstrated no hypoglycemic episodes, while one had recurrence of hypoglycemia and underwent distal pancreatectomy. Procedural mortality was 0% and morbidity 8.3%. CONCLUSION: Patients suffering from severe recurrent hypoglycemia after GBS can be treated, in most cases, just by restoration of gastric restriction. Distal pancreatectomy should be considered a second-line treatment.

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. METHODS: The study group contained 290 severely obese patients undergoing bariatric surgery between August 1996 and September 2004 [BPD: n = 103, 64.1% women, age 43 +/- 1 years (mean +/- SEM), BMI 53.9 +/- 0.9 kg/m(2), weight 153.4 +/- 2.9 kg; Roux-en-Y gastric bypass: n = 126, 73.0% women, age 43 +/- 1 years, BMI 44.2 +/- 0.3 kg/m(2), weight 123.8 +/- 1.5 kg; adjustable gastric banding (AGB): n = 61, 57.4% women, age 44 +/- 1 years, BMI 49.9 +/- 0.5 kg/m(2), weight 146.1 +/- 2.0 kg). Changes in bowel habits, flatulence, flatus odor, and effects on social life were estimated at least 4 months after surgery using a self-administered questionnaire. RESULTS: Fecal consistency changed significantly after surgery. Loose stools and diarrhea were more frequent after BPD and RYGB (P < 0.001) but more so after BPD than after either RYGB or AGB (P < 0.002). Constipation was more likely after AGB (P = 0.03). In addition, malodorous flatus affecting social life was more frequent after BPD than after either RYGB or AGB (P < 0.003). Furthermore, flatus frequency increased after BPD and RYGB, and patients were more bothered by their malodorous flatus than after AGB (all P < 0.001). Flatus severity score was highest in BPD, intermediate in RYGB, and lowest in AGB patients (all P < 0.001), a difference that was not influenced by frequency of metabolic syndrome before and after surgery. Moreover, observation period after surgery had no influence on overall results of bowel habits. Subsore quality of life bariatric analysis and reporting outcome system (BAROS) scores were largely similar between all three groups. However, flatulence severity score correlated inversely with quality of life estimated by BAROS in BPD and RYGB, but not in AGB patients. CONCLUSIONS: The type of bariatric surgery affects bowel habits in an operation-specific manner, resulting mainly in diarrhea after BPD and RYGB, and constipation after AGB. Flatulence severity impairs quality of life most in BPD, is intermediate in RYGB, and is only minor after AGB, a phenomenon that was only partially mirrored in quality-of-life measures of BAROS.