Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study.

BACKGROUND: The cardiometabolic risk profile improves following bariatric surgery. However, the degree of improvement in relation to weight-stable control subjects is unknown. OBJECTIVES: To study the differences in cardiometabolic risk profile between formerly obese patients following Roux-en-Y gastric bypass (RYGB) surgery and control subjects. METHODS: Subjects undergoing RYGB and reaching a BMI <30 kg m-2 2 years postsurgery were matched with control subjects regarding age, sex and BMI. The following examinations were performed: insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, insulin clearance, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile, inflammatory marker levels, dual-energy X-ray absorptiometry and subcutaneous adipose tissue cellularity (fat cell size and number). RESULTS: Sixty-nine subjects undergoing RYGB were matched to a control subject. Insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, blood pressure, inflammatory status and glucose, triglyceride and HDL cholesterol levels were comparable to values of control subjects. However, HOMA-IR (1.0 ± 0.5 vs. 1.3 ± 0.7, P = 0.005), insulin clearance (0.38 ± 0.08 vs. 0.34 ± 0.08 µL m-2  min-1 , P < 0.0001) and circulating levels of insulin (31 ± 15 vs. 37 ± 17 pmol L-1 , P = 0.008), total cholesterol (4.1 ± 0.7 vs. 4.8 ± 0.9 mmol L-1 , P < 0.0001) and LDL cholesterol (2.1 ± 0.6 vs. 2.9 ± 0.8 mmol L-1 , P < 0.0001) were improved beyond the levels in matched control subjects. Furthermore, formerly obese subjects had higher lean and lower fat mass as well as a more benign type of adipose cellularity (hyperplasia with many small fat cells) compared to control subjects. CONCLUSIONS: Subjects who underwent RYGB and reached a postobese state demonstrated a beneficial body composition, slightly increased insulin sensitivity as indirectly measured by HOMA-IR and higher insulin clearance, lower atherogenic lipid/lipoprotein levels and benign adipocyte morphology compared with control subjects who had never been obese. In line with previous results, our findings may in part explain why RYGB confers long-term protection against metabolic complications.

Alcohol and substance abuse, depression and suicide attempts after Roux-en-Y gastric bypass surgery.

BACKGROUND: Small studies suggest that subjects who have undergone bariatric surgery are at increased risk of suicide, alcohol and substance use disorders. This population-based cohort study aimed to assess the incidence of treatment for alcohol and substance use disorders, depression and attempted suicide after primary Roux-en-Y gastric bypass (RYGB). METHODS: All patients who underwent primary RYGB in Sweden between 2001 and 2010 were included. Incidence of hospital admission for alcohol and substance use disorders, depression and suicide attempt was measured, along with the number of drugs prescribed. This cohort was compared with a large age-matched, non-obese reference cohort based on the Swedish population. Inpatient care and prescribed drugs registers were used. RESULTS: Before RYGB surgery, women, but not men, were at higher risk of being diagnosed with alcohol and substance use disorder compared with the reference cohort. After surgery, this was the case for both sexes. The risk of being diagnosed and treated for depression remained raised after surgery. Suicide attempts were significantly increased after RYGB. The adjusted hazard ratio for attempted suicide in the RYGB cohort after surgery compared with the general non-obese population was 2·85 (95 per cent c.i. 2·40 to 3·39). CONCLUSION: Patients who have undergone RYGB are at an increased risk of being diagnosed with alcohol and substance use, with an increased rate of attempted suicide compared with a non-obese general population cohort.

Changes in eating behaviour and food choices in families where the mother undergoes gastric bypass surgery for obesity.

BACKGROUND/OBJECTIVES: There is a lack of research exploring the effects of Roux-en-Y gastric bypass (RYGB) surgery on the patient's family's eating behaviour and food choices. The aim of the current study was to investigate changes in partners' and children's eating behaviour and food choices following maternal RYGB. SUBJECTS/METHODS: Sixty-nine women and their families were recruited from RYGB waiting lists at five Swedish surgical clinics. Data were collected during home visits 3 months before and 9 months after RYGB. Anthropometrical measures were taken, the adults completed the Three-Factor Eating Questionnaire and the children completed the Children's Eating Attitudes Test (ChEAT). All participants also completed a short food frequency questionnaire. RESULTS: Changes in scores were analysed using paired t-tests for unadjusted estimates or linear regression models with robust variance (General Estimating Equations) in order to enable age- and sex-adjusted estimates for the children. There were no meaningful differences in the partners' eating behaviour or food choices. The boys, but not the girls, improved their ChEAT scores, as did the overweight/obese children in comparison with the normal-weight children. The boys, unlike the girls, also decreased their intake of soft drinks, as did the normal-weight children when compared with the overweight/obese children. CONCLUSIONS: No clear-cut changes were found in partners' eating behaviour and food choices. Eating attitudes and soft drinks intake were improved among boys but not among girls. Differing modelling behaviour may partially explain these findings, but available data did not allow us to understand the underlying mechanisms.

Formation of the Scandinavian Obesity Surgery Registry, SOReg.

BACKGROUND: Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. METHOD: In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. RESULTS: After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that >98% of data are correct. All results are publicized annually on the Internet. COMMENTS: Using this systematic approach, it has been possible to cover >99% of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects.

BACKGROUND: Cardiovascular disease is associated with multiple risk factors including stiff arteries and large adipocytes. Whether the latter two are interrelated is unknown. We aimed to determine whether arterial stiffness is associated with fat cell size and number in subcutaneous or visceral white adipose tissue (WAT). METHODS: A cross-sectional study of 120 obese subjects scheduled for bariatric surgery in whom WAT mass and distribution was assessed by dual-X-ray absorptiometry. Biopsies from visceral (greater omentum) and subcutaneous (abdominal) WAT were obtained to calculate fat cell volume and number. Arterial stiffness was determined as aortic pulse wave velocity (PWV). RESULTS: Visceral adipocyte volume, but not number, was strongly (P<0.0001) and positively correlated with PWV, explaining 20% of the inter-individual variations in this parameter. This relationship remained significant after correction for clinical confounders. PWV correlated positively (r=0.38, P<0.0001) with visceral (but not subcutaneous) WAT mass. Furthermore, PWV was also positively associated with subcutaneous adipocyte volume (r=0.20, P=0.031) and negatively with fat cell number (r=-0.26, P=0.006). However, the relationships between PWV and visceral WAT mass or subcutaneous fat cell size/number became non-significant when controlling for visceral fat cell volume. In a multiple regression analysis to determine the factors that explain variations in PWV, only visceral fat cell volume, age, pulse rate and diastolic blood pressure entered the model, together explaining 42% of the variation in PWV. CONCLUSIONS: Visceral fat cell volume was the only WAT parameter that constituted an independent and significant, positive regressor for arterial stiffness determined by PWV. Although a causal relationship is not established, visceral fat cell volume may explain the well-known correlation between central fat mass, arterial stiffness and cardiovascular risk, at least in severely/morbidly obese subjects.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake.

BACKGROUND/OBJECTIVES: A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS: Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m(2)). RESULTS: Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (-102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=-0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=-0.44; P=0.01). CONCLUSIONS: Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Differences in gestational weight gain between pregnancies before and after maternal bariatric surgery correlate with differences in birth weight but not with scores on the body mass index in early childhood.

BACKGROUND: Large maternal gestational weight gain (GWG) is associated with increased birth weight and increased risk of obesity in offspring, but these associations may be confounded by genetic and environmental factors. The aim was to investigate the effects of differences in GWG in all three trimesters on differences in birth weight and in body mass index (BMI) scores at 4 and 6 years of age, within siblings born before and after bariatric surgery. METHOD: Women with at least one child born before and one after bariatric surgery were identified in national Swedish registers. Series of weight (and height) measurements were collected from antenatal medical records, with data on the nearest pregnancies before and after bariatric surgery. RESULTS: The age-adjusted means of pre- and post-operative GWG of 124 women were 11.3 (standard deviation [SD] 7.2) and 8.3 (SD 6.4) kg, respectively (P = 0.01). Adjusted fixed effects regression models showed positive associations of differences in mean total GWG with differences in siblings' birth weight, 0.023 kg per 1-kg greater weight gain (95% confidence interval [CI]: 0.014-0.069) and for second trimester 0.53 kg for each 1-kg greater weight per week (95% CI: 0.32-1.61), whereas no associations were found with BMI in pre-school age. CONCLUSION: This study showed positive associations between differences in total and second trimester maternal GWG and differences in children's birth weight, but no association with BMI scores in pre-school age. Maternal genetic, social and lifestyle factors fixed from one pregnancy to the next were taken into account in the analyses by the study design.

Waist circumference to assess reversal of insulin resistance following weight reduction after bariatric surgery: cohort and cross-sectional studies.

OBJECTIVE: To validate the use of waist circumference to assess reversal of insulin resistance after weight loss induced by bariatric surgery. DESIGN: In cross-sectional studies, threshold values for insulin resistance were determined with homeostasis model assessment of insulin resistance (HOMA-IR) (algorithm based on fasting plasma glucose and insulin) in 1018 lean subjects and by hyperinsulinemic euglycemic clamp (clamp) in 26 lean women. In a cohort study on 211 patients scheduled for bariatric surgery, HOMA-IR and waist circumference were measured before and 1.5-3 years after weight reduction. In a subgroup of 53 women, insulin sensitivity was also measured using clamp. RESULTS: The threshold for insulin resistance (90th percentile) was 2.21 (mg dl(-1) fasting glucose × mU l(-1) fasting insulin divided by 405) for HOMA-IR and 6.118 (mg glucose per kg body weight per minute) for clamp. Two methods to assess reversal of insulin resistance by measuring waist circumference were used. A single cutoff value to <100 cm for waist circumference was associated with reversal of insulin resistance with an odds ratio (OR) of 49; 95% confidence interval (CI)=7-373 and P=0.0002. Also, a diagram based on initial and weight loss-induced changes in waist circumference in patients turning insulin sensitive predicted reversal of insulin resistance following bariatric surgery with a very high OR (32; 95% CI=4-245; P=0.0008). Results with the clamp cohort were similar as with HOMA-IR analyses. CONCLUSIONS: Reversal of insulin resistance could either be assessed by a diagram based on initial waist circumference and reduction of waist circumference, or by using 100 cm as a single cutoff for waist circumference after weight reduction induced by bariatric surgery.

Semaphorin 3C is a novel adipokine linked to extracellular matrix composition.

AIMS/HYPOTHESIS: Alterations in white adipose tissue (WAT) function, including changes in protein (adipokine) secretion and extracellular matrix (ECM) composition, promote an insulin-resistant state. We set out to identify novel adipokines regulated by body fat mass in human subcutaneous WAT with potential roles in adipose function. METHODS: Adipose transcriptome data and secretome profiles from conditions with increased/decreased WAT mass were combined. WAT donors were predominantly women. In vitro effects were assessed using recombinant protein. Results were confirmed by quantitative PCR/ELISA, metabolic assays and immunochemistry in human WAT and adipocytes. RESULTS: We identified a hitherto uncharacterised adipokine, semaphorin 3C (SEMA3C), the expression of which correlated significantly with body weight, insulin resistance (HOMA of insulin resistance [HOMAIR], and the rate constant for the insulin tolerance test [KITT]) and adipose tissue morphology (hypertrophy vs hyperplasia). SEMA3C was primarily found in mature adipocytes and had no direct effect on human adipocyte differentiation, lipolysis, glucose transport or the expression of ß-oxidation genes. This could in part be explained by the significant downregulation of its cognate receptors during adipogenesis. In contrast, in pre-adipocytes, SEMA3C increased the production/secretion of several ECM components (fibronectin, elastin and collagen I) and matricellular factors (connective tissue growth factor, IL6 and transforming growth factor-ß1). Furthermore, the expression of SEMA3C in human WAT correlated positively with the degree of fibrosis in WAT. CONCLUSIONS/INTERPRETATION: SEMA3C is a novel adipokine regulated by weight changes. The correlation with WAT hypertrophy and fibrosis in vivo, as well as its effects on ECM production in human pre-adipocytes in vitro, together suggest that SEMA3C constitutes an adipocyte-derived paracrine signal that influences ECM composition and may play a pathophysiological role in human WAT.

Intravenous ghrelin accelerates postoperative gastric emptying and time to first bowel movement in humans.

BACKGROUND: Ghrelin has been shown to stimulate gastric emptying in healthy humans and patients with delayed gastric emptying. The aim of this study is to assess the effect of ghrelin on gastric emptying on day 2 after open colorectal surgery. METHODS: Twenty-four patients (mean age 69.2 ± 1.4, BMI 25.8 ± 0.8 kg m(-2) ) were randomized to saline or ghrelin infusion (15 pmol kg(-1)  min(-1) ) during 3 h before and on day 2 after open colorectal surgery. Of these, 20 were assessed both before and after surgery. At start of infusion, a liquid meal (480 kcal, 200 mL) was administered together with 1.5 g acetaminophen. Plasma was obtained at regular intervals together with visual analogue scales for hunger, satiety and nausea. Acetaminophen was analyzed as a marker of gastric emptying. Plasma glucose, insulin, acyl-ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinoptrophic peptide (GIP), pancreatic polypeptide and peptide YY (PYY) were analyzed. KEY RESULTS: Gastric emptying was faster during ghrelin infusion compared to saline before and after surgery (P < 0.02). In addition, plasma glucose was increased (P < 0.05). With ghrelin infusion, plasma insulin was unchanged except for lower values postoperatively (P < 0.05). Ghrelin did not alter plasma concentrations of gut peptides. After surgery, ghrelin shortened the time to first bowel movement compared to saline (2.1 ± 0.3 vs 3.5 ± 0.4 days, P = 0.02). CONCLUSIONS & INFERENCES: A 3-h ghrelin infusion increased the gastric emptying rate and hastened the time to first bowel movement after surgery. Ghrelin/ghrelin receptor agonists have a therapeutic potential in postoperative ileus; Karolinska Clinical Trial Registry nr CT20110084.

Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis.

OBJECTIVE: The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. METHODS: 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann-Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. RESULTS: Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. CONCLUSION: The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. ADVANCES IN KNOWLEDGE: The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level.

The effects of weight loss strategies on gastric emptying and appetite control.

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g. sleeve gastrectomy and Roux-en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying, which we hypothesize will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g. diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.

Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides.

CONTEXT: Endocrine effects of gastric bypass (GBP) surgery for obesity on glucose homeostasis are not fully understood. MAIN OBJECTIVE: The main objective of the study was to assess the changes in plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), leptin, somatostatin, glucose-dependent insulinotropic peptide, enteroglucagon, and glucagon early after GBP. METHOD: Twelve obese subjects (body mass index 45.3 ± 1.9 kg/m(2)) were subjected to a liquid meal without lipids before and 3 d, 2 months, and 1 yr after GBP. Plasma concentrations of glucose, insulin, leptin, and gut peptide hormones were assessed before and for 180 min after the meal. Satiety was measured with visual analog scales. The absorption rate of acetaminophen added to the liquid meal was measured. Insulin resistance was measured by the homeostasis model assessment of insulin resistance. RESULTS: All subjects lost weight (body mass index 30.3 ± 1.8 kg/m(2) at 1 yr). Fasting glucose was significantly lower on d 3 (P < 0.05). There was a progressive decrease in the homeostasis model assessment of insulin resistance after 2 months postoperatively. Postprandially, there was a progressive rise of GLP-1 and enteroglucagon and a transient increase in pancreatic glucagon release over the study period. There was a leftward shift of the time course of plasma glucose and insulin. Somatostatin release was lower on d 3 (P < 0.05) but then unchanged. The absorption rate of acetaminophen was twice as fast after GBP compared with before surgery and did not change over time. Satiety scores increased markedly postoperatively. CONCLUSION: Both enhanced insulin sensitivity and incretin hormones, such as GLP-1, contribute to the early control of glucose homeostasis. Progressively increasing postprandial levels of enteroglucagon (oxyntomodulin) and GLP-1 facilitate weight loss and enhance insulin effectiveness.

Morbidity and mortality before and after bariatric surgery for morbid obesity compared with the general population.

BACKGROUND: Bariatric surgery reduces morbidity and mortality in obese subjects, but it is unclear how rates compare with those in the population. The aim was to assess the risk of admission to hospital for obesity-related co-morbidities and overall mortality after bariatric surgery in relation to the general population. METHODS: A nationwide, population-based cohort study was conducted of all patients who underwent bariatric surgery in Sweden between 1980 and 2006. Each patient was compared with ten age- and sex-matched controls randomly selected from the Total Population Register. Hospital admission for co-morbidities was identified through the Patient Register. Cox proportional regression was used to calculate hazard ratios (HRs). RESULTS: A total of 13 273 patients underwent bariatric surgery between 1980 and 2006. After surgery, the overall adjusted HR remained increased for myocardial infarction (HR 1·56, 95 per cent confidence interval 1·35 to 1·81), angina pectoris (HR 2·05, 1·84 to 2·31), stroke (HR 2·13, 1·88 to 2·42), hypertension (HR 2·80, 2·61 to 3·01), diabetes (HR 2·44, 2·23 to 2·67) and death (HR 1·24, 1·15 to 1·34) in these patients compared with the general population. The 4161 patients who underwent gastric bypass surgery no longer had a higher risk of diabetes (HR 1·23, 0·88 to 1·72) or myocardial infarction (HR 0·78, 0·42 to 1·45), whereas morbidity remained increased after restrictive surgery in 7855 patients. The adjusted mortality remained higher after both gastric bypass and restrictive surgery. CONCLUSION: Gastric bypass, but not restrictive surgery, in patients with morbid obesity seems to reduce the risk of diabetes and myocardial infarction to population levels, but the risk of death remains increased.

Gender differences in the effect of fish oil on appetite, inflammation and nutritional status in haemodialysis patients.

BACKGROUND: Haemodialysis patients show signs of chronic inflammation and reduced appetite, which is associated with a worse clinical status and an increased mortality risk. Fish oil has anti-inflammatory properties and may be useful as a therapeutic treatment. There is limited evidence to indicate the feasibility and efficacy of this intervention in dialysis patients. The present study aimed to compare the effect of 12 weeks of supplementation with fish oil on markers of appetite and inflammation in male and female haemodialysis patients. METHODS: The study was conducted in 28 haemodialysis patients. All patients were prescribed 3 g of fish oil per day for 12 weeks. Changes in appetite, plasma fatty acid profiles and inflammatory markers were measured at baseline and at 12 weeks. RESULTS: The mean (SD) increase in percent plasma eicosapentaenoic acid was statistically significant [1.1 (0.8) to 4.1 (2.2), P < 0.001], which was a strong indicator of good adherence. There were trends towards reductions in peptide YY (-9%; P = 0.078) and an increase in subjective sensations of hunger (+12%; P = 0.406), which reflects an increase in motivation to eat. Males (n = 13) experienced a more marked increase in hunger compared to females (+23% versus -6%), which was associated with maintenance in C-reactive protein and interleukin-6, and a reduction in soluble intercellular adhesion molecule-1. CONCLUSIONS: The results obtained demonstrate meaningful trends towards improvements in subjective appetite and certain inflammatory markers (although no change in dietary intake) and this effect was more pronounced in males. However, the levels of some inflammatory markers increased in females and this requires further study. The high level of adherence achieved indicates that an intervention requiring patients to consume four fish oil capsules per day is achievable. This was a short-term study and the effects need to be confirmed in a randomised controlled trial.

Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986-2006 in Sweden.

AIMS/HYPOTHESIS: Symptomatic hypoglycaemia with related confusion, syncope, epilepsy or seizures is a newly recognised complication of gastric bypass surgery for obesity. The incidence of these conditions is not known. We therefore studied the incidence of post-gastric bypass hypoglycaemia and related symptoms in patients who have undergone gastric bypass and a reference cohort from the general population of Sweden. METHODS: This is a nationwide cohort study based on national registries with 5,040 persons who underwent gastric bypass, vertical banded gastroplasty or gastric banding for obesity in Sweden between 1 January 1986 and 31 December 2006 and a cohort of ten referents per patient matched for sex and age randomly sampled from the general population. The incidence rates of hospitalisation for hypoglycaemia, confusion, syncope, epilepsy or seizures before and after dates of surgery or inclusion in the reference cohort were studied. RESULTS: Preoperative incidences of hospitalisation for hypoglycaemia were similar in the surgical and referent cohorts. After gastric bypass surgery, the adjusted hazard ratios were significantly elevated for hypoglycaemia (2.7 [95% CI 1.2-6.3]), confusion (2.8 [1.3-6.0]), syncope (4.9 [3.4-7.0]), epilepsy (3.0 [2.1-4.3]) and seizures (7.3 [5.0-10.8]). The proportions of gastric bypass patients and reference participants affected by hypoglycaemia were very low (0.2% and 0.04%, respectively). There was no increased risk of hypoglycaemia after vertical banded gastroplasty or gastric banding compared with the referent population. CONCLUSIONS/INTERPRETATION: Obese persons who have undergone gastric bypass have an increased risk of hospitalisation for diagnoses associated with post-gastric bypass hypoglycaemia, although few patients are affected.

Bariatric surgery reduces mortality in Swedish men.

BACKGROUND: Mortality is lower in obese patients who have undergone surgery for obesity than in those who have not. The majority of patients in these studies have been women. Perioperative mortality is known to be higher among men, and this may counterbalance the survival advantage seen after surgery. This cohort study compared mortality among operated obese patients, non-operated obese patients and a general control cohort of men. METHODS: The study was based on record linkage between Swedish registries. An operated obese, a non-operated obese and a general control cohort were created. The two non-operated cohorts were assigned pseudosurgery dates. Data regarding preoperative and postoperative morbidity were collected, as well as mortality data. RESULTS: Hazard ratios were calculated for mortality between the cohorts adjusting for preoperative morbidity and age. Comparison of all-cause mortality for the obese surgical and non-surgical cohorts gave an adjusted mortality risk of 0.7 (95 per cent confidence interval (c.i.) 0.5 to 1.0) (P = 0.039); the adjusted mortality risk was 1.5 (95 per cent c.i. 1.1 to 2.0) (P = 0.011) when the obese surgical cohort was compared with the general control cohort. CONCLUSION: Bariatric surgery reduces overall mortality in obese men.

Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans.

BACKGROUND: Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. METHODS: Ghrelin (15 pmol kg(-1) min(-1)) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. KEY RESULTS: The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 +/- 3.9 vs 59.9 +/- 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. CONCLUSIONS & INFERENCES: The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.

Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery.

AIM: Compare the response to oral glucose of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) at 1 year after restrictive vs. malabsorptive bariatric surgery. METHODS: Vertical banded gastroplasty (VBG, n = 7) or jejunoileal bypass (JIB, n = 5) was performed in 12 women, aged 26-39 years, with severe obesity [body mass index (BMI) 46.6 +/- 2.3 kg/m(2)]. After 1 year, 75 g glucose was administered and plasma levels of glucose, insulin, GIP and GLP-1 were determined regularly during the following 2 h. RESULTS: At 1 year after operation, reduction in body weight, actual body weight, fasting glucose or insulin, or the glucose and insulin responses to oral glucose did not differ significantly between the groups. Similarly, fasting GIP and GLP-1 levels did not differ significantly between the groups. In contrast, the GIP and GLP-1 responses to oral glucose were different between the groups in a dissociated pattern. Thus, AUC(GIP) was significantly higher after VBG than after JIB (53 +/- 8 vs. 26 +/- 6 pmol/l/min, p = 0.003). In contrast, AUC(GLP-1) was significantly higher after JIB than after VBG (49 +/- 5 vs. 20 +/- 3 pmol/l/min, p = 0.007). CONCLUSIONS: We conclude that at 1 year after bariatric surgery, the two incretins show dissociated responses in that the GIP secretion is higher after VBG whereas GLP-1 secretion is higher after JIB. This dissociated incretin response is independent from reduction in body weight, glucose tolerance or insulin secretion.