glucagon-like-peptide-1 and Obesity--Morbid

The study aimed to perform a meta-analysis about the change in adipokines and gastrointestinal hormones after bariatric surgery in patients with obesity.. We searched the Cochrane Central Register of Controlled Trials, EMBASE, and PubMed for related articles and used Review Manager 5.4 for data aggregation. Sensitivity and subgroup analysis were also conducted when feasible.. As a result, 95 articles involving 6232 patients were included in the meta-analysis. After bariatric surgery, the levels of leptin, ghrelin, C-reactive protein (CRP), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis, factor-α (TNF-α), and interleukin-1β (IL-1β) reduced, while adiponectin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels increased significantly. Subgroup analysis indicated that there was a more significant reduction in leptin level with a longer follow-up time. OAGB had a greater effect on increasing adiponectin level compared with other procedures. SG procedure would bring about reduced ghrelin, while BPD resulted in increased ghrelin. Meta-regression analysis found that publication year, study design, number of patients, preoperative age, preoperative BMI, and quality assessment score were not significantly related to change in leptin, adiponectin, and ghrelin levels.. Bariatric surgery was associated with a significant decrease in leptin, ghrelin, CRP, IL-6, Hs-CRP, TNF-α, and IL-1β, as well as increase in adiponectin, GLP-1, and PYY levels.

Topics: Adipokines; Adiponectin; Bariatric Surgery; C-Reactive Protein; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Interleukin-6; Leptin; Obesity, Morbid; Peptide YY; Tumor Necrosis Factor-alpha

With a rise in obesity and more patients opting for bariatric surgery, it becomes crucial to understand associated complications like postprandial hypoglycemia (PPH). After bariatric surgery, significant changes are seen in insulin sensitivity, beta cell function, glucagon-like peptide 1 (GLP-1) levels, the gut microbiome, and bile acid metabolism. And in a small subset of patients, exaggerated imbalances in these functional and metabolic processes lead to insulin-glucose mismatch and hypoglycemia. The main treatment for PPH involves dietary modifications. For those that do not respond, medications or surgical interventions are considered to reverse some of the imbalances. We present a few case reports of patients that safely tolerated GLP-1 agonists. However, larger randomized control trials are needed to further characterize PPH and understand its treatment.

Topics: Bariatric Surgery; Blood Glucose; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Insulin; Obesity, Morbid

Severe obesity among adolescent shows a worrisome trend in regard to its increasing prevalence and poses a great challenge for treatment. Conservative measures have modest effects on weight loss, usually fail in achieving a sustainable weight loss and resolution of comorbidities. This has led to greater utilization of bariatric surgery (BS) that offers a fast reduction in body mass index with little perioperative complications. Despite the increasing utilization of BS, data are still insufficient, regarding their long-term outcome in adolescents. We review short- and long-term effects of BS and their implications on bone health and nutritional deficiencies in adolescents. In addition, we discuss possible pharmaceutical alternatives.. BS results in a substantial weight loss of roughly 37% in the first-year post-operation and is superior to conservative measures in resolution of metabolic comorbidities. BS significantly improves health-related quality of life. Longer follow-up (F/U) shows weight regain in 50% of patients. Furthermore, reduced bone mass and nutritional deficiencies were reported in up to 90% of patients. Most recently, alternative to BS became more relevant with approval of GLP-1 analogues use in adolescents. GLP-1 analogues are potent enough to induce moderate clinically meaningful weight loss and improvement of metabolic component.. We conclude that obese adolescents without major obesity-related complications may benefit from pharmacological interventions with lifestyle modification. We advise considering BS as treatment approach in adolescents with severe obesity and major obesity-related complications with proper preoperative preparation and postoperative F/U in excellence centers.

Topics: Adolescent; Bariatric Surgery; Glucagon-Like Peptide 1; Humans; Malnutrition; Obesity, Morbid; Pediatric Obesity; Quality of Life; Weight Loss

To perform a structured systematic review and meta-analysis to evaluate changes in ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and gastric inhibitory peptide (GIP) gut hormone levels in patients after sleeve gastrectomy.. Despite sleeve gastrectomy becoming the most common surgical weight loss procedure, weight loss mechanisms remain less clear.. Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed through April 1, 2019, in accordance with PRISMA and MOOSE guidelines. Randomized controlled trials and prospective observational studies evaluating pre and post-procedure hormones fasting ghrelin, postprandial GLP-1, postprandial PYY, and fasting GIP levels were included. Hedge g with random-effects models were used to determine pooled effect size and corresponding 95% confidence intervals (CIs).. A total of 28 studies (n = 653; 29.56% male) were included. Mean age was 42.00 ± 5.48 years, with average follow-up of 11.70 ± 11.38 months. Pre-procedure body mass index (BMI) was 46.01 ± 4.07 kg/m with a postsleeve gastrectomy BMI of 34.07 ± 3.73 kg/m, representing total body weight loss of 25.13 ± 4.44% and excess weight loss of 57.48 ± 9.64% (P < 0.001). Ghrelin decreased (Hedge g -1.486, 95% CI -1.884 to -1.089, I = 91.95%), whereas GLP-1 and PYY increased post-procedure (Hedge g 1.095, 95% CI 0.509 to 1.642, I = 84.38%; and Hedge g 1.396, 95% CI 0.781 to 2.011, I = 84.02%, respectively). GIP did not significantly change (Hedge g -0.213, 95% CI -1.019 to 0.592, I = 79.65%).. Fasting ghrelin levels decreased, whereas postprandial GLP-1 and PYY increased after sleeve gastrectomy. Fasting GIP levels remained unchanged. Future studies are needed to assess the role of these gut hormones and relationship to weight loss and metabolic outcomes.

Topics: Biomarkers; Gastrectomy; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY

The evidence is strong that bariatric surgery is superior to medical treatment in terms of weight loss and comorbidities in patients with severe obesity. However, a considerable part of patients presents with unsatisfactory response in the long term. It remains unclear whether postoperative administration of glucagon-like peptide-1 analogues can promote additional benefits. Therefore, a systematic review of the current literature on the management of postoperative GLP-1 analogue usage after metabolic surgery was performed. From 4663 identified articles, 6 met the inclusion criteria, but only one was a randomized controlled trial. The papers reviewed revealed that GLP-1 analogues may have beneficial effects on additional weight loss and T2D remission postoperatively. Thus, the use of GLP-1 analogues in addition to surgery promises good results concerning weight loss and improvements of comorbidities and can be used in patients with unsatisfactory results after bariatric surgery.

Topics: Bariatric Surgery; Complementary Therapies; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Randomized Controlled Trials as Topic

Considering conflicting results on the consequences of all types of obesity surgery, we were to summarize them via a systematic review.. Electronic literature search was done via scientific search engines. After the removal of duplicates and selection of articles of interest, 771 studies were included.. Insulin resistance indicators were significantly improved after bariatric surgery. Leptin was also significantly decreased while adiponectin was significantly increased. Although the level of metabolic hormones changed after bariatric surgery, they were not statistically significant. Inflammation indicators were significantly decreased. Significant reduction was also detected in PAI-1 and sICAM-1.. Bariatric surgery is beneficial in morbidly obese patients. Although treating obesity in a surgical way may cause some complications, the weight loss is generally safe and effective.

Topics: Adiponectin; Bariatric Surgery; C-Reactive Protein; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Obesity, Morbid; Peptide YY; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alpha

We review current evidence regarding changes in bile acid (BA) metabolism, transport, and signaling after bariatric surgery and how these might bolster fat mass loss and energy expenditure to promote improvements in type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD).. The two most common bariatric techniques, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), increase the size and alter the composition of the circulating BA pool that may then impact energy metabolism through altered activities of BA targets in the many tissues perfused by systemic blood. Recent reports in human patients indicate that gene expression of the major BA target, the farnesoid X receptor (FXR), is increased in the liver but decreased in the small intestine after RYGB. In contrast, intestinal expression of the transmembrane G protein-coupled BA receptor (TGR5) is upregulated after surgery. Despite these apparent conflicting changes in receptor transcription, changes in BAs after both RYGB and VSG are associated with elevated postprandial systemic levels of fibroblast growth factor 19 (from FXR activation) and glucagon-like peptide 1 (from TGR5 activation). These signaling activities are presumed to support fat mass loss and related metabolic benefits of bariatric surgery, and this supposition is in agreement with findings from rodent models of RYGB and VSG. However, inter-species differences in BA physiology limit direct translation and mechanistic understanding of how changes in individual BA species contribute to post-operative improvements of T2D and NAFLD in humans. Thus, details of all these changes and their influences on BAs' biological actions are still under scrutiny. Changes in BA physiology and receptor activities after RYGB and VSG likely support weight loss and promote sustained metabolic improvements.

Topics: Bariatric Surgery; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fibroblast Growth Factors; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Non-alcoholic Fatty Liver Disease; Obesity, Morbid; Postprandial Period; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Signal Transduction; Weight Loss

Roux-en-Y gastric bypass (RYGB) is an effective treatment for diabetes. Glucagon-like peptide-1 (GLP-1) is a gut hormone that is important to glucose homeostasis.. This study aimed to assess GLP-1 level and its predictors after RYGB.. The study design was a meta-analysis. The data sources were MEDLINE, EMBASE, Web of Science, and the Cochrane Databases. The study selection composed of studies with pre- and post-RYGB levels. The main outcomes were as follows: Primary outcome was the change in postprandial GLP-1 levels after RYGB. Secondary outcomes included the changes in fasting glucose, fasting insulin, and fasting GLP-1 levels after RYGB. Meta-regression to determine predictors of changes in GLP-1 levels was performed. Outcomes were reported using Hedge's g.. Twenty-four studies with 368 patients were included. Postprandial GLP-1 levels increased after RYGB (Hedge's g = 1.29, p < 0.0001), while fasting GLP-1 did not change (p = 0.23). Peak postprandial GLP-1 levels gave the most consistent results (I. Postprandial GLP-1 levels increase after RYGB, while fasting levels remain unchanged. Shorter Roux limb length is associated with greater increase in postprandial GLP-1, which may lead to better glycemic control in this population.

Topics: Blood Glucose; Fasting; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Obesity, Morbid; Postprandial Period; Treatment Outcome; Weight Loss

Roux-en-Y gastric bypass (RYGB) is an efficient treatment for morbid obesity and reduces obesity-related co-morbidities. With the growing number of patients undergoing gastric bypass, complications now demand further attention. Postprandial hyperinsulinemic hypoglycemia (PHH) after Roux-en-Y gastric bypass is a complex condition, characterized by increased glucose variability including both hyperglycemic and hypoglycemic values. PHH seems to be more prevalent than previously suggested and is highly dependent on the choice of diagnostic tool, which has not yet been standardized. Questionnaires, an oral glucose tolerance test, a mixed meal tolerance test, and continuous glucose monitoring have been used, each with their own advantages. The condition is further complicated by a large group of asymptomatic cases. Patients with symptoms of PHH after gastric bypass are characterized by exaggerated insulin and glucagon-like peptide-1 responses compared to asymptomatic operated patients. The counter-regulatory mechanisms responsible for preventing hypoglycemia appear to be altered. The cause of these changes is not entirely understood, and it remains difficult to identify patients at risk of developing hypoglycemia. Known risk factors are female sex, longer time since surgery, and lack of prior diabetes. Management of the hypoglycemic episodes is difficult, and only dietary modifications consisting of frequent and less carbohydrate-rich meals seem to be efficient. Medical treatments and surgical procedures have been attempted in few studies and still warrant further examination.

Topics: Biomarkers; Blood Glucose; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Male; Monitoring, Ambulatory; Obesity, Morbid; Postoperative Complications; Postprandial Period; Risk Factors; Sex Factors

Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear. Recent research suggests that changes in the concentrations of plasma bile acids might contribute to these metabolic changes after surgery. In this review, we aimed to outline the potential role of bile acids in SWRD. We systematically reviewed MEDLINE, SCOPUS, and Web of Science for articles reporting the effect of SWRD on outcomes published between 1969 and 2016. We found that changes in circulating bile acids after surgery may play a major role through activation of the farnesoid X receptor A (FXRA), the fibroblast growth factor 19 (FGF19), and the G protein-coupled bile acid receptor (TGR5). Bile acid concentration increased significantly after RYGB. Some studies suggest that a transitory decrease occurs at 1 week post-surgery, followed by a gradual increase. Most studies have shown the increase to be proportionate by all bile acid subtypes. Bile acids can regulate glucose metabolism through the expression of TGR5 receptor in L cells, resulting in a release of glucagon-like peptide 1 (GLP-1). It may also induce the synthesis and secretion of FGF19 in ileal cells, thereby improving insulin sensitivity and regulating glucose metabolism. All the present SWRD are involved with changes in food stimulation to the stomach. This implies that discovering and developing the antagonists to TGR5 and FXRA may effectively control metabolic syndrome and the elucidation of the mechanisms underlying the physiological effects related to weight loss and T2D remission after surgery may help to identify new drug targets.

Topics: Bile Acids and Salts; Diabetes Mellitus, Type 2; Fibroblast Growth Factors; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Obesity, Morbid

Bariatric surgery is a gastrointestinal procedure that has emerged as the most effective treatment for weight loss. Roux-en-Y gastric bypass and sleeve gastrectomy are the main procedures currently performed. However, the benefits of bariatric surgery extend beyond weight loss. In fact, improvements in β-cell function occur before clinically meaningful weight loss and contribute to type 2 diabetes mellitus (T2D) remission. Herein, we discuss evidence supporting the efficacy of bariatric surgery for weight loss and improved insulin secretion in patients with and without T2D. The exact mechanism by which bariatric surgery elicits a favorable change in β-cell function remains unclear, but a leading hypothesis is that rerouted nutrient flow to the gut alters enteroendocrine hormone production (e.g., glucagon-like polypeptide 1, polypeptide tyrosine-tyrosine, ghrelin), gut microbiome metabolites (e.g., lipopolysaccharides, short-chain fatty acids), and circulating bile acid changes that favor appetite suppression, metabolic rate, and insulin action. We also highlight the role of adipose-derived factors (e.g., pancreatic fat content, adiponectin) that may have an effect on β-cell function, as well as discuss the clinical determinants of diabetes remission (e.g., age and T2D duration). Taken together, the acute improvements seen with bariatric surgery are weight-independent and likely related to incretin-mediated effects on postprandial glucose metabolism and insulin sensitivity. Over longer periods of time, increases in bile acids, reductions in pancreatic lipid content, and elevated adiponectin levels may also contribute to reduced disease risk. As a result, the gut appears to be a novel target for favorably preventing and treating obesity-related metabolic disorders.

Topics: Adiponectin; Adipose Tissue; Bariatric Surgery; Bile Acids and Salts; Caloric Restriction; Cytokines; Diabetes Mellitus, Type 2; Fatty Acids, Volatile; Gastrointestinal Hormones; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Obesity, Morbid; Postoperative Period

Roux-en-Y gastric bypass (RYGB) surgery induces weight loss of 20-30% that is maintained for 20 years. In patients with type 2 diabetes, the glucose-lowering effect of RYGB is superior to conventional antidiabetic therapy and often occurs within days after surgery. The aim of the thesis was to investigate the physiological mechanisms responsible for improved glycaemic control with special focus on the early postoperative period. We therefore investigated insulin sensitivity, insulin clearance and pancreatic islet-cell function in patients with type 2 diabetes and in glucose tolerant subjects prior to and at 1 week, 3 months and 1 year after RYGB. Hepatic insulin sensitivity measured with a glucose tracer increased already 1 week after RYGB, whereas peripheral insulin sensitivity estimated with the hyperinsulinaemic euglycaemic clamp was unchanged. Concomitant increases in insulin clearance at 1 week further highlights the liver as an important organ responsible for the early effects on glucose metabolism after surgery since insulin predominantly is cleared by the liver. Rapid improvements in hepatic insulin sensitivity is a common observation after calorie restriction in obese patients and has been observed as early as after 48 hours in absence of major weight loss and changes in peripheral insulin sensitivity. Thus, calorie restriction is a likely explanation for our findings of early improvements in hepatic insulin sensitivity and insulin clearance after RYGB. Peripheral insulin sensitivity increased along with weight loss at 3 months and 1 year after RYGB. Beta-cell function increased after RYGB in patients with type 2 diabetes in response to oral glucose, whereas insulin secretion was unchanged in response to an intravenous (iv) glucose-glucagon test throughout the first year after surgery. In glucose tolerant subjects, the insulin response to iv glucose-glucagon declined after RYGB likely as an adaptation to increased insulin sensitivity. The secretion of glucagon-like peptide 1 (GLP-1) increased substantially in both groups in response to oral glucose, whereas the secretion of glucose-dependent insulinotropic poly-peptide (GIP) was largely unchanged postoperatively. The insulinotropic effects of the incretin hormones were preserved after surgery during iv infusion in glucose tolerant subjects. Increased insulin secretion postoperatively was thus linked to the oral and not the iv route of administration highlighting the importance of the changed gast

Topics: Anastomosis, Roux-en-Y; Blood Glucose; Body Mass Index; Denmark; Female; Follow-Up Studies; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity, Morbid; Quality of Life; Treatment Outcome; Weight Loss

Bariatric surgery is arguably the most effective therapy for weight loss, and Rouen-Y gastric bypass (RYGB) is considered the "gold-standard" procedure. However, sleeve gastrectomy (SG) surgery has become more prevalent in recent years and it is unclear if weight loss differences occur between these procedures. Herein, we discuss evidence from randomized clinical trials comparing the effectiveness of RYGB and SG on weight loss. Moreover, we highlight gut hormones (e.g., GLP-1, ghrelin, bile acids, etc.) as potentially important mechanisms that contribute to the durability of decreased appetite and opposed fat storage following RYGB and SG. Collectively, although a subtle (∼ 3-5 kg) weight loss difference may exist in favor of RYGB up to 3 years post-operation, it appears that RYGB and SG induce comparable weight loss and changes in gut physiology that parallel reduced disease risk. These findings are clinically relevant for optimizing treatment strategies that combat obesity-related diabetes and cardiovascular disease.

Topics: Bile Acids and Salts; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Weight Loss

Bariatric surgery has emerged as the most durably effective treatment of type 2 diabetes (DM). However, the mechanisms governing improvement in glucose homeostasis have yet to be fully elucidated. In this review we discuss the various types of surgical interventions and the multitude of factors that potentially mediate the effects on glycemia, such as altered delivery of nutrients to the distal ileum, duodenal exclusion, gut hormone changes, bile acid reabsorption, and amino acid metabolism. Accumulating evidence that some of these changes seem to be independent of weight loss questions the rationale of using body mass index as the major indication for surgery in diabetic patients. Understanding the complex mechanisms and interactions underlying improved glycemic control could lead to novel therapeutic targets and would also allow for greater individualization of therapy and optimization of surgical outcomes.

Topics: Bariatric Surgery; Body Mass Index; Caloric Restriction; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucose; Glycated Hemoglobin; Homeostasis; Humans; Incretins; Insulin Resistance; Male; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Weight Loss

Topics: Asian People; Bariatric Surgery; Diabetes Mellitus, Type 2; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Obesity, Morbid

Glucagon like peptide-1 (GLP-1) is one of the gastrointestinal peptides implicated in glycaemic homeostasis. In non-obese individuals with normal glucose tolerance GLP-1 is secreted in response to nutrient intake. However, this GLP- 1 response is generally accepted to be significantly diminished in those with diabetes, obesity or both. Given that GLP-1 is secreted from enteroendocrine L cells in the intestine, it is not surprising that manipulation of the gastro- intestinal tract has been shown to alter GLP-1 secretion; particularly when this intestinal manipulation is designed to aid weight reduction. GLP-1 dynamics are altered by bariatric surgery, with an improved secretory response to nutrient intake. However, there remains debate on the mechanisms responsible for the alterations in GLP-1 dynamics. Here we review the evidence for GLP-1 dynamics after Roux-en-Y gastric bpyass (RYGB), adjustable gastric banding (AGB), biliopancreatic diversion (BPD) and sleeve gastrectomy (SG), and make comparisons between modalities. In addition, we review the potential mechanisms underlying these dynamics, other molecules that may add to the "incretin effect" and other possible roles for GLP-1 following bariatric surgery. Finally, we will offer our critique of the evidence base.

Topics: Animals; Biliopancreatic Diversion; Blood Glucose; Cross-Sectional Studies; Fasting; Female; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Incretins; Longitudinal Studies; Male; Neural Pathways; Obesity, Morbid; Peptide YY; Prospective Studies; Rats; Weight Loss

Bariatric surgery managing/preventing complications of severe overweight is nowadays widely accepted as a mainstay in the treatment of morbid obesity. Its role is particularly important in type 2 diabetes developing on the base of long-standing significant overweight. The glycemic control improves within days-weeks after these surgeries, when weight loss and reduction of the visceral fat mass is barely detectable. This short term effect is probably due to an increased secretion of glucagon-like peptide and, as a consequence, an improvement in hepatic insulin sensitivity as well as the whole body glucose uptake. Besides the prolonged glucagon-like peptide effects, the favourable long term effect of these operations - lasting for 10 years even after surgery - is the decrease of visceral fat mass and elimination of harmful influence of cytokines produced by the fatty tissue. The article overviews the metabolic effects of these procedures, their undoubted advantages and potential risks.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Hungary; Insulin; Insulin Resistance; Intra-Abdominal Fat; Male; Obesity, Morbid; Peptide YY; United States; Weight Loss

Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one.

Topics: Amides; Anti-Obesity Agents; Anticonvulsants; Antidepressive Agents; Basal Metabolism; Benzazepines; Benzoxazines; Body Mass Index; Bridged Bicyclo Compounds, Heterocyclic; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Combined Modality Therapy; Cyclobutanes; Dexfenfluramine; Fatty Acids; Female; Fenfluramine; Glucagon-Like Peptide 1; Human Growth Hormone; Humans; Intestinal Absorption; Lactones; Leptin; Life Style; Liraglutide; Male; Norepinephrine; Obesity; Obesity, Morbid; Orlistat; Piperidines; Pyrazoles; Pyridines; Receptor, Melanocortin, Type 4; Rimonabant; Satiation; Serotonin; Sodium-Glucose Transport Proteins; Sucrose; Thyroid Hormones

Roux-en-Y gastric bypass (RYGB) greatly improves glycaemic control in morbidly obese patients with type 2 diabetes, in many even before significant weight loss. Understanding the responsible mechanisms may contribute to our knowledge of the pathophysiology of type 2 diabetes and help identify new drug targets or improve surgical techniques. This review summarises the present knowledge based on pathophysiological studies published during the last decade. Taken together, two main mechanisms seem to be responsible for the early improvement in glycaemic control after RYGB: (1) an increase in hepatic insulin sensitivity induced, at least in part, by energy restriction and (2) improved beta cell function associated with an exaggerated postprandial glucagon-like peptide 1 secretion owing to the altered transit of nutrients. Later a weight loss induced improvement in peripheral insulin sensitivity follows.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity, Morbid; Time Factors; Treatment Outcome

Type 2 diabetes mellitus is increasing over time as result of the obesity epidemics. In fact, the prevalence of Type 2 diabetes across Europe in 2010 was estimated to be 8.2% of the population and its projection for 2030 sees figures of 10.1%. This increase in the number of diabetic individuals has also dramatically raised the health expense, with spending on diabetes in Europe in 2010 accounting for 10% of the total healthcare cost. A meta-analysis of the literature evidenced that the clinical and laboratory manifestations of Type 2 diabetes are resolved in 78.1%, and are improved in 86.6% of obese patients (body mass index >35 kg/m²) after bariatric surgery. However, a gradation of effects of different surgical techniques in improving glucose control does exist, with the largest and durable effects observed in prevalently malabsorptive procedures. The outcome of bariatric surgery on insulin sensitivity and secretion is different in relation to the type of operation performed. In fact, while Roux-en-Y Gastric Bypass enhances insulin secretion after a meal thus improving glucose metabolism, Bilio-Pancreatic Diversion acts through the amelioration of insulin sensitivity allowing a subsequent reduction of insulin hypersecretion, which is a typical feature of the insulin resistance state. Gastric banding action is mediated uniquely through the weight loss, and the effect of sleeve gastrectomy is still to be elucidated. Incretin secretion is dramatically increased under nutrient stimulation after gastric bypass leading, probably, to an overstimulation of pancreatic β-cells resulting in the increase of insulin secretion.

Topics: Animals; Bariatric Surgery; Body Mass Index; Diabetes Mellitus, Type 2; Gastric Mucosa; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Humans; Incretins; Insulin Resistance; Insulin-Secreting Cells; Intestinal Mucosa; Obesity, Morbid

Bariatric surgery is the most effective method for promoting dramatic and durable weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved in over 80% of patients. The mechanisms behind the amelioration in metabolic abnormalities are largely unknown but may be due to changes in energy metabolism, gut peptides and food preference. The goal of this meeting was to review the latest research to better understand the mechanisms behind the 'magic' of bariatric surgery. Replication of these effects in a non-surgical manner remains one of the ultimate challenges for the treatment of obesity and diabetes. Promising data on energy metabolism, gastrointestinal physiology, hedonic response and food intake were reviewed and discussed.

Topics: Bariatric Surgery; Energy Metabolism; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Weight Loss

Gastric bypass surgery (GBP) results in important and sustained weight loss and remarkable improvement of Type 2 diabetes. The favorable change in the incretin gut hormones is thought to be responsible, in part, for diabetes remission after GBP, independent of weight loss. However, the relative role of the change in incretins and of weight loss is difficult to differentiate. After GBP, the plasma concentrations of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide increase postprandially by three- to fivefold. The postprandial incretin effect on insulin secretion, blunted in diabetes, improves rapidly after the surgery. In addition to the change in incretins, the pattern of insulin secretion in response to oral glucose changes after GBP, with recovery of the early phase and significant decrease in postprandial glucose levels. These changes were not seen after an equivalent weight loss by diet. The improved insulin release and glucose tolerance after GBP were shown by others to be blocked by the administration of a GLP-1 antagonist, demonstrating that the favorable metabolic changes after GBP are, in part, GLP-1 dependent. The improved incretin levels and effect persist years after GBP, but their long-term effect on glucose metabolism, and on hypoglycemia post GBP are yet unknown. Understanding the mechanisms by which incretin release is exaggerated postprandially after GBP may help develop new less invasive treatment options for obesity and diabetes. Changes in rate of eating, gastric emptying, intestinal transit time, nutrient absorption and sensing, as well as bile acid metabolism, may all be implicated.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Intestine, Small; Obesity, Morbid; Remission Induction; Weight Loss

The clinical outcomes achieved by bariatric surgery have been impressive. However, the physiologic mechanisms and complex metabolic effects of bariatric surgery are only now beginning to be understood. Ongoing research has contributed a large amount of data and shed new light on the science behind obesity and its treatment, and this article reviews the current understanding of metabolic and bariatric surgery physiology.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Neuropeptide Y; Obesity, Morbid; Peptide YY; Weight Loss

Roux-en-Y gastric bypass is a well-accepted tool for the treatment of obesity and, compared to conventional weight loss methods (eg, diet and exercise) and other weight loss surgeries (eg, gastric banding), it results in considerable weight loss that is maintained long term. Although successful, the mechanisms for weight loss are not completely understood and it is thought that gastrointestinal hormones play a role. Several gastrointestinal hormones have been identified for their effects on appetite, including glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), leptin, and ghrelin. This review encompasses a literature search that included 45 primary articles and shows that there are alterations in GLP-1, PYY, leptin, and ghrelin postoperatively. GLP-1 and PYY concentrations were usually found to be higher, whereas ghrelin levels were typically lower post- Roux-en-Y gastric bypass than in individuals with obesity, those who were overweight or of normal weight, and in those who underwent procedures other than Roux-en-Y gastric bypass or who achieved weight loss by lifestyle modification. An understanding of how gastrointestinal hormones change after Roux-en-Y gastric bypass may help dietetics practitioners optimize nutrition care for this patient population. A review of the literature also highlighted some research gaps that should be taken into consideration when designing future studies.

Topics: Appetite Regulation; Follow-Up Studies; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

This review analyzes the literature concerning gut peptides and bariatric surgery, from 2005 to July 2009. In particular, we are interested in whether, and how, gastrointestinal peptide alterations following surgery interfere with appetite/satiety, and what role they might play in the resolution of comorbidities.. PubMed/MEDLINE and ISI Web of Knowledge were used to search for human studies concerning gut peptides profiles after any bariatric operation technique.. Most of the studies reviewed had longitudinal design, short follow-up, and low statistical power. The diversity of study results may be partially explained by methodological aspects. Glucagon-like peptide-1, gastric inhibitory peptide, and peptide YY alterations may contribute to the excellent results in glycemic control of diabetics. Results do vary depending on bariatric operation technique; this is particularly evident in the case of ghrelin, which has been much studied in recent years. Ghrelin suppression has been linked to increased satiety, alterations in energy homeostasis, and better glucose metabolism.. There is a lack of long-term data on gastrointestinal hormone profiles after bariatric surgery and the studies have many methodological pitfalls. We still need prospective, long-term, good methodological studies in this area.

Topics: Appetite Regulation; Bariatric Surgery; Diabetes Mellitus, Type 2; Energy Metabolism; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Obesity, Morbid; Peptide Hormones; Peptide YY; Satiation

Obesity has become an epidemic in the United States and is reaching epidemic levels in many other countries. Although obesity itself can have deleterious effects, the attributed comorbidities contribute greatly to the overall health decline of affected populations. Overweight and obese individuals are at increased risk for many diseases and health conditions. Medical, psychological, and endoscopic therapies for weight loss have been tried; however weight loss is usually only modest, with weight regain common. Bariatric surgery has been reported to be the most effective method for achieving major, long-term weight loss, with weight loss ranges of 35%-40% lasting as long as 15 years. Patients often lose weight at a rapid rate, with resolution or remission of many obesity-related comorbidities. Although the procedure itself plays a role in the weight loss after surgery, the resultant metabolic changes have been linked to alterations in the gut hormones. Although these changes have been the focus of much research, they are not completely understood. Two hypotheses have been proposed to explain this conflicting data. The hindgut hypothesis suggests that the quick transit of nutrients to the distal bowel improves glucose metabolism by stimulating secretion of glucagon-like peptide-1 and other appetite-suppressing gut peptides. The foregut hypothesis suggests that there is a yet unknown factor that promotes insulin resistance and type 2 diabetes mellitus. Further research is essential and could lead to less invasive therapies with fewer complications and side effects than bariatric surgery.

Topics: Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Gluconeogenesis; Humans; Insulin; Insulin Secretion; Intestine, Small; Obesity, Morbid; Weight Loss

Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated.

Topics: Animals; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Gastric Bypass; Gastric Emptying; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Gluconeogenesis; Glucose; Homeostasis; Humans; Incretins; Intestine, Small; Leptin; Liver; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Weight Loss

Diabetes resolves in 80% of individuals undergoing successful Roux-en-Y gastric bypass. Absolute caloric restriction alone resulting from gastric anatomic changes indeed leads to weight loss; however, immediate effects in glycemic control often precede substantial weight loss typically associated with insulin sensitivity. One putative explanation relates to hormonal effects accompanying Roux-en-Y gastric bypass. We reviewed the existing and recent literature to investigate the hormonal changes accompanying Roux-en-Y gastric bypass.. Changes in levels of five candidate enteric hormones have been recently associated with early postoperative glycemic control following Roux-en-Y gastric bypass; the strongest effects are seen with variations in glucagon-like peptide-1, glucose-dependent insulinotropic peptide and ghrelin.. The unique hybridization of static anatomic restriction and dynamic absorptive bypass lends a duality to the beneficial effects of Roux-en-Y gastric bypass. This duality likely explains the short-term and long-term resolution of diabetes in patients undergoing Roux-en-Y gastric bypass.

Topics: Caloric Restriction; Diabetes Mellitus, Type 2; Energy Intake; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Incretins; Obesity, Morbid; Peptide Hormones; Weight Loss

Bariatric surgery is the only effective treatment for morbid obesity in the long term. Gut hormones are key players in the metabolic mechanisms causing obesity. Furthermore gut hormones are involved in the signalling process of hunger and satiety which leads to the control of nutrient intake. In this review, the role of these hormones as facilitators of appetite control after bariatric and metabolic surgery will be explored.

Topics: Animals; Appetite Regulation; Bariatric Surgery; Cholecystokinin; Eating; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Obesity, Morbid; Peptide YY; Satiation; Satiety Response; Weight Loss

Bariatric surgery represents the main option for obtaining substantial and long-term weight loss in morbidly obese subjects. In addition, malabsorptive (biliopancreatic diversion, BPD) and restrictive (roux-en-Y gastric bypass, RYGB) surgery, originally devised to treat obesity, has also been shown to help diabetes. Indeed, type 2 diabetes is improved or even reversed soon after these operations and well before significant weight loss occurs. Two hypotheses have been proposed to explain the early effects of bariatric surgery on diabetes--namely, the hindgut hypothesis and the foregut hypothesis. The former states that diabetes control results from the more rapid delivery of nutrients to the distal small intestine, thereby enhancing the release of hormones such as glucagon-like peptide-1 (GLP-1). The latter theory contends that exclusion of the proximal small intestine reduces or suppresses the secretion of anti-incretin hormones, leading to improvement of blood glucose control as a consequence. In fact, increased GLP-1 plasma levels stimulate insulin secretion and suppress glucagon secretion, thereby improving glucose metabolism. Recent studies have shown that improved intestinal gluconeogenesis may also be involved in the amelioration of glucose homoeostasis following RYGB. Although no large trials have specifically addressed the effects of bariatric surgery on the remission or reversal of type 2 diabetes independent of weight loss and/or caloric restriction, there are sufficient data in the literature to support the idea that this type of surgery--specifically, RYGB and BPD--can lead to early improvement of glucose control independent of weight loss.

Topics: Bariatric Surgery; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Gluconeogenesis; Humans; Insulin; Insulin Secretion; Intestine, Small; Obesity, Morbid; Stomach; Weight Loss

Obesity plays a key role in the pathophysiology of type 2 diabetes (T2DM), and weight loss is a major objective, although difficult to achieve with medical treatments. Bariatric surgery has proven its efficacy in obtaining marked and sustained weight loss, and is also associated with a significant improvement in glucose control and even diabetes remission. Roux-en-Y gastric bypass appears to be more effective in diabetic patients than the restrictive gastroplasty procedure. This may be explained not only by greater weight reduction, but also by specific hormonal changes. Indeed, increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may lead to improved beta-cell function and insulin secretion as well as reduced insulin resistance associated with weight loss. The presence of T2DM in obese individuals is a further argument to propose bariatric surgery, and even more so when diabetes is difficult to manage by medical means and other weight-related complications may occur. Bariatric surgery is associated with a better cardiovascular prognosis and reduced mortality, even though acute and long-term complications are present. The observation that surgical rerouting of nutrients triggers changes in the release of incretin hormones that, in turn, ameliorate the diabetic state in the absence of weight loss has led to the recent development of innovative surgical procedures. Thus, bariatric surgery may be said to be progressing towards so-called 'metabolic surgery', which merits further evaluation in patients with T2DM within a multidisciplinary approach that involves both surgeons and endocrinologists.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin Secretion; Obesity, Morbid; Prognosis; Risk Factors; Weight Loss

This article aims to critically review the literature, describing the possible implications of different bariatric surgery techniques in gastrointestinal peptides and their relation with the neural paths involved in the central regulation of appetite and satiety: the gut-brain axis.. Bariatric surgery operations change orexigenic and anorexigenic gastrointestinal peptide levels. Forty-one studies were analyzed in order to understand the effects of different operations on the behavior of gut peptides (ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1, gastric inhibitory polypeptide, pancreatic polypeptide). The authors have tried to correlate these findings with weight loss/maintenance via different surgical techniques.. The present line of research is recent and there is a lack of comparability between studies. There are different design approaches and study protocols, different laboratorial exams. Prospective long-term studies with larger samples are needed to clarify the effects of bariatric operations on the gut-brain axis.

Topics: Appetite Regulation; Bariatric Surgery; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Pancreatic Polypeptide; Peptide Hormones; Peptide YY; Satiety Response; Weight Loss

The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increasing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass procedures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and biliopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resistance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms.

Topics: Biomarkers; Blood Glucose; Body Mass Index; Caloric Restriction; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Male; Obesity, Morbid; Peptide Fragments; Peptide Hormones; Prognosis; Protein Precursors; Treatment Outcome; Weight Loss

Morbid obesity is a serious health problem associated with disease and mortality. One such disease is non-insulin-dependent diabetes mellitus (NIDDM). Approximately 95% of American diabetics have NIDDM. One of the major causes for type 2 diabetes is obesity. The improvement of diabetes with weight control is not in the earliest description of the disease. However, dietary control of NIDDM is often disappointing. Diet can improve glucose metabolism in obesity, but the improvement usually represents only a portion or a brief return to euglycemia, even when patients appear to be compliant. In contrast, reversal of NIDDM has been much more successfully achieved after bariatric surgery. Intra-abdominal fat deposition is associated with increased plasma concentration of free fatty acids, which reduce insulin sensitivity at both muscular and hepatic sites. The progression of diabetes is heralded by the inability of the beta-cells to maintain their previously high rate of insulin secretion in response to glucose, in the face of insulin resistance. The propensity to develop type 2 diabetes may be genetically determined or triggered by environmental factors. The connection between diabetes and obesity represents a continuum that progresses through different phases in which defective insulin action is the principal problem. At this point, we are unable to correlate the different findings of the many questions that arise, such as: 1) Does the decrease in sensitivity to insulin result from rearrangement of the insulin receptor? 2) Is weight loss the trigger for decrease of insulin resistance? 3) Is rearrangement of part of the intestine a mechanism to trigger the secretion of hormones (incretins) that help in insulin response? 4) Which mechanism controls the insulin resistance? The goal of this paper is to review literature on incretins and address the role of incretins after bariatric surgery. We know very little about the action of incretins in diabetes. We will assess the interaction between the secretion of incretins and bariatric surgery for the cure of diabetes.

Topics: Acyl Coenzyme A; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Lipolysis; Obesity, Morbid; Peptide Fragments; Peptide Hormones; Peptide YY; Protein Precursors

This is a review of intestinal glucagon, which is released when undigested food is in the terminal ileum.. In the early 1980s, Koopmans and Sclafani showed in fat rats that the transposition of a short segment of ileum to the duodenum would decrease weight just as effectively as intestinal bypass. Sarson and coworkers found elevated enteroglucagon after biliopancreatic diversion (BPD). Scopinaro has observed that patients with diabetes who undergo BPD are cured of diabetes and do not experience a recurrence. Näslund and associates showed recently a high level of plasma glucagon-like peptide (GLP-1) 20 years after jejunoileal bypass. GLP-1 has been shown to be an effective medication for treatment of type 2 diabetes mellitus (DM). It must be given parenterally. It has been used only in short, well-controlled studies.. It appears from all that is now known about GLP-1 that ileal transposition would be an ideal operation for treatment of type 2 DM. Release of enteroglucagon from the ileum has probably contributed to weight control in bypass operations for obesity, but the effect has been obscured by the associated malabsorption. The release of GLP-1 after meals has probably been beneficial to patients treated with gastric bypass who had type 2 DM. This is a recommendation for well-planned studies of ileal transposition in the treatment of type 2 DM and obesity. Ileal transposition is not recommended for general use until such studies have shown safety, efficacy, and the requirements for patient selection.

Topics: Animals; Biliopancreatic Diversion; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Ileum; Obesity, Morbid; Peptide Fragments; Protein Precursors; Rats

Glycemic control, after metabolic surgery, is achieved in two stages, initially with neuroendocrine alterations and in the long-term with sustainable weight loss. The resection of the gastric fundus, as the major site of ghrelin production, is probably related with optimized glucose regulation. The aim of the present study is to investigate whether the modification of laparoscopic Roux-en-Y gastric bypass (LRYGBP) with fundus resection offers superior glycemic control, compared to typical LRYGBP.. Participants were 24 patients with body mass index (BMI) ≥40kg/m. Ninety-five percent of patients showed complete remission of T2DM after 12 months. LRYGBP+FR was not related with improved glycemic control, compared to LRYGBP. Ghrelin levels were not significantly reduced at 6 and 12 months after LRYGBP+FR. GLP-1 and PYY levels were remarkably increased postprandially in both groups at 6 and 12 months postoperatively (p<0.01). Patients who underwent LRYGBP+FR achieved a significantly lower BMI at 12 months in comparison to LRYGBP (p<0.05).. Fundus resection is not associated with improved glycemic regulation, compared to typical LRYGBP and the significant decrease in BMI after LRYGBP+FR has to be further confirmed with longer follow-up.

Topics: Diabetes Mellitus, Type 2; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Glucose; Humans; Laparoscopy; Obesity, Morbid; Peptide YY

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery.. To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD).. Subanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups.. Twenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery.. Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention.. Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB.. Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.

Topics: Adult; Aged; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Infusions, Subcutaneous; Male; Metabolomics; Middle Aged; Obesity, Morbid; Oxyntomodulin; Peptide YY; Single-Blind Method; Treatment Outcome; Weight Loss; Young Adult

Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and β-cell function in type 2 diabetes remains unclear.. We aimed to compare gastrointestinal hormones and β-cell function, assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery, hypothesizing higher glucagon-like peptide-1 (GLP-1) levels and greater β-cell response to glucose after RYGB than after SG.. This study was a randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcomes were diabetes remission and IVGTT-derived β-cell function. Participants with obesity and type 2 diabetes were allocated (1:1) to RYGB or SG. We measured gastrointestinal hormone profiles and insulin secretion as β-cell glucose sensitivity (β-GS) derived from 180-minute OGTTs.. Participants were 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1 year were higher after RYGB than after SG (77% vs 48%; P = 0.002). Incremental area under the curve (iAUC0-180) GLP-1 and β-GS increased more after RYGB than after SG, with 1-year between-group difference 1173 pmol/L*min (95% CI, 569-1776; P = 0.0010) and 0.45 pmol/kg/min/mmol (95% CI, 0.15-0.75; P = 0.0032), respectively. After surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher β-GS and higher GLP-1 secretion.. RYGB was associated with greater improvement in β-cell function and higher postprandial GLP-1 levels than SG.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Obesity, Morbid; Postprandial Period; Treatment Outcome

Following Roux-en-Y gastric bypass (RYGB), positive alterations are observed in gut microbiota and intestinal peptides. Previous studies demonstrated similar alterations observed in cases when pre-probiotics are used without surgery. The aim of this trial was to evaluate the effectiveness of early use of pre-probiotics after RYGB.. The operation and follow-up of the patients were performed at Istanbul University Medical Faculty. Thirty-two patients who had undergone RYGB were randomized to pre-probiotic group (PreProBG, n = 16; 200 g/day yogurt plus 10 g/day inulin+oligofructose) and probiotic group (ProBG, n = 16; 200 g/day yogurt only) for 6 months. Blood samples (glucose, insulin, A1c, GLP-1, PYY), anthropometric measurements, and appetite ratings have been evaluated at baseline and 3 (m3) and 6 (m6) months after RYGB.. Initial anthropometric measurements and appetite ratings decreased significantly after surgery and there were no significant differences between the groups. The decrease of area under the curve(insulin) was less and has a positive correlation with the changes in anthropometric measurements in PreProBG. GLP-1 and PYY which increased dramatically after surgery in all patients were higher in PreProBG. But this increase had a negative correlation with the changes in anthropometric measurements during the study.. Increased insulin, GLP-1, and PYY secretion was more enhanced by pre-probiotic use in early postoperative period. But this increase not only in anthropometric measurements but also in appetite ratings affects negatively, contrary to expectations. In summary, it should be investigated with new studies that use of pre-probiotics in the late postoperative period may be more effective in patients with weak insulin and incretin response and therefore insufficient weight loss. Trial Registration clinicaltrials.gov Identifier: NCT03517345.

Topics: Blood Glucose; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Obesity, Morbid; Probiotics; Prospective Studies

Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly. Two single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions.. In study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones.. In RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB.

Topics: Adult; Bile Acids and Salts; Blood Glucose; C-Peptide; Colesevelam Hydrochloride; Female; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Male; Middle Aged; Neurotensin; Obesity, Morbid; Postprandial Period; Single-Blind Method

The aim of this study was to compare the effect of antral resection versus antral preservation sleeve gastrectomy on the post-operative GLP-1, glycemic control, and weight loss in adolescents suffering from severe obesity and type 2 diabetes (T2D).. This study included 36 adolescents. Patients were randomly divided into 2 groups: group (A) and group (B). Each group included 18 patients who underwent LSG, starting transection at 2 cm or 5 cm from the pyloric ring in group (A) and group (B), respectively. They were followed up at 1, 3, 6, 12, and 24 months post-operatively. The outcomes were the post-operative GLP-1 response, glycemic control, weight loss, and safety.. The improvements in the body mass index and the percentage of excess weight loss (%EWL) were statistically significant within each group. The mean GLP-1 levels showed significant increase at the 1, 3, and 6 months but not in the 12 and 24 months in all the studied samples within each group. The mean HbA1c levels and post-prandial serum C-peptide significantly improved within each group (P < 0.05). No statistical differences in the weight loss, %EWL, GLP-1, HbA1c, C-peptide changes, and complication rates were observed between both groups. Diabetic remission was significantly higher (88.9%) in group (A).. LSG resulted in generalized significant GLP-1 initial response that decreased over time. The reduced antrum size did not influence the GLP-1 response, glycemic control, or insulin resistance, but resulted in significantly better T2D remission. Since the study examines a small number of patients, further studies are needed.. ClinicalTrials.gov Identifier: NCT04388059.

Topics: Adolescent; Body Mass Index; Diabetes Mellitus, Type 2; Gastrectomy; Glucagon-Like Peptide 1; Glycemic Control; Humans; Laparoscopy; Obesity, Morbid; Pediatric Obesity; Treatment Outcome; Weight Loss

To compare changes in bone mineral density (BMD) in patients with morbid obesity and type 2 diabetes (T2D) a year after being randomized to metabolic gastric bypass (mRYGB), sleeve gastrectomy (SG), and greater curvature plication (GCP). We also analyzed the association of gastrointestinal hormones with skeletal metabolism.. Forty-five patients with T2D (mean BMI 39.4 ± 1.9 kg/m. After surgery, the decrease at femoral neck (FN) was similar but at lumbar spine (LS), it was greater in the mRYGB group compared with SG and GCP - 7.29 (4.6) vs. - 0.48 (3.9) vs. - 1.2 (2.7)%, p < 0.001. Osteocalcin and alkaline phosphatase increased more after mRYGB. Bone mineral content (BMC) at the LS after surgery correlated with fasting ghrelin (r = - 0.412, p = 0.01) and AUC for GLP-1 (r = - 0.402, p = 0.017). FN BMD at 12 months correlated with post-surgical fasting glucagon (r = 0.498, p = 0.04) and insulin AUC (r = 0.384, p = 0.030) and at LS with the AUC for GLP-1 in the same time period (r = - 0.335, p = 0.049). However, in the multiple regression analysis after adjusting for age, sex, and BMI, the type of surgery (mRYGB) remained the only factor associated with BMD reduction at LS and FN.. mRYGB induces greater deleterious effects on the bone at LS compared with SG and GCP, and gastrointestinal hormones do not play a major role in bone changes.

Topics: Adult; Bariatric Surgery; Bone and Bones; Bone Density; Bone Remodeling; Diabetes Mellitus, Type 2; Female; Femur Neck; Follow-Up Studies; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Treatment Outcome

Sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are among the commonly performed bariatric procedures. This randomized study aimed to compare SG and OAGB in terms of weight loss, improvement in comorbidities, and change in serum ghrelin and glucagon-like peptide-1 (GLP-1) levels.. This was a prospective randomized trial on patients with morbid obesity associated with medical comorbidities who were randomly assigned to 1 of 2 equal groups; group I underwent SG and group II underwent OAGB. Outcome measures were percent of excess weight loss (%EWL), improvement in comorbidities, change in the venous levels of fasting ghrelin and postprandial GLP-1 at 12 months after surgery, in addition to operation time and complications.. Forty patients (38 female) of a mean age of 33.8 years and mean body mass index of 48.6 kg/m2 were included. Operation time in group II was significantly longer than in group I (86 vs. 52.87 min; P<0.001). There were 6 recorded complications (1 in group I and 5 in group II, P=0.18). The %EWL, %total weight loss, and %excess body mass index loss at 6 and 12 months postoperatively were significantly higher in group II than in group I. Both groups had similar rates of improvement in comorbidities. Group I had significantly lower ghrelin and GLP-1 levels postoperatively at 6 and 12 months, respectively, as compared with group II.. OAGB was associated with significantly higher EWL than SG. The reduction in fasting ghrelin and postprandial GLP-1 serum levels at 12 months after SG was significantly higher than that after OAGB.

Topics: Adult; Fasting; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Obesity, Morbid; Prospective Studies

There is limited literature available on the long-term effect of bariatric surgery especially laparoscopic sleeve gastrectomy (LSG) on the incretin hormone response.. Our primary aim was to investigate changes in glucose metabolism and incretin hormone responses in participants with impaired glucose regulation approximately 4 years after LSG. The secondary aim was to examine the long-term incretin hormone changes of biliopancreatic diversion (BPD).. A non-randomised prospective study comprising of 10 participants undergoing LSG and 6 participants undergoing BPD. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were performed during an oral glucose tolerance test pre-operatively and 1 month, 6 months and at approximately 4-7 years post-operatively. Area under the curve (AUC) was examined at 60 and 120 min.. In the LSG group, a significant reduction in 2-h plasma glucose (2 h PG), HbA1c and HOMA-IR was observed at 4 years. Compared with pre-operative levels, significant increases in post-glucose GLP-1 secretion were observed at 1 and 6 months, but not maintained at 4 years. A linear increase was seen in post-glucose GIP response at 1 month and 6 months and 4 years. Within the BPD group, a reduction in HbA1c along with an increase GLP-1 response was observed at 7 years.. An increase in GLP-1 response was not preserved at 4 years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.

Topics: Adult; Blood Glucose; C-Peptide; Female; Follow-Up Studies; Gastrectomy; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Incretins; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Prospective Studies; Time Factors

To investigate the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide on post-bariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass.. In a randomized crossover study, 11 women who had undergone Roux-en-Y gastric bypass and had documented hypoglycaemia were each evaluated during a baseline period without treatment and during five treatment periods with the following interventions: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks and pasireotide 300 μg as a single dose. Treatment effects were evaluated by a mixed-meal tolerance test (MMTT) and, for all treatment periods except pasireotide, by 6 days of continuous glucose monitoring (CGM).. Treatment with acarbose and treatment with pasireotide both significantly lifted nadir glucose levels (mean ± SEM 3.9 ± 0.2 and 7.9 ± 0.4 vs 3.4 ± 0.2; P < .03) and reduced time in hypoglycaemia during the MMTTs. Acarbose reduced peak glucose levels and time in hyperglycaemia, whereas pasireotide greatly increased both variables. Acarbose and pasireotide reduced insulin and C-peptide levels, and pasireotide also diminished glucagon-like peptide-1 levels. Sitagliptin lowered nadir glucose values, while verapamil and liraglutide had no effect on hypoglycaemia. During the CGM periods, the treatments had no impact on hypoglycaemia, whereas acarbose and liraglutide reduced hyperglycaemia and glycaemic variability.. In an experimental setting, treatment with acarbose and pasireotide reduced PBH. Acarbose appears to have an overall glucose-stabilizing effect, whereas pasireotide leads to increased and sustained hyperglycaemia.

Topics: Acarbose; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Obesity, Morbid; Postoperative Complications; Postprandial Period; Sitagliptin Phosphate; Somatostatin; Treatment Outcome; Verapamil

This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation.. This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS).. Modified BPD does not lead to significant changes in satiety evaluated by the VAS; different aspects of satiety regulation are correlated with the postprandial levels of GLP-1 (hunger feeling) and GLP-2 (satiation feeling and desire to eat) 1 year after modified BPD, signaling a specific postoperative gut hormone-related modulation of appetite.

Topics: Adult; Appetite Regulation; Biliopancreatic Diversion; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Male; Middle Aged; Obesity, Morbid; Pilot Projects; Postoperative Period; Postprandial Period; Satiation

Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits.. We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers.. Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter.. Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed.. This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.

Topics: Adult; Analysis of Variance; Area Under Curve; Body Mass Index; Cross-Over Studies; Energy Metabolism; Female; Follow-Up Studies; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Infusions, Subcutaneous; Male; Middle Aged; Obesity, Morbid; Oxyntomodulin; Pain Measurement; Patient Safety; Peptide YY; Risk Assessment; Single-Blind Method; Treatment Outcome; United Kingdom; Volunteers

Our aim was to determine the predictive value of gut hormone changes for the improvement of type 2 diabetes (T2D) following metabolic Roux-en-Y gastric bypass (mRYGB), sleeve gastrectomy (SG), and greater curvature plication (GCP) in a randomized controlled trial. Contradictory results have been obtained regarding the role of gastrointestinal hormones (in particular GLP-1) in beneficial metabolic bariatric surgery outcomes.. Forty-five patients with T2D (mean BMI 39.4 ± 1.9 kg/m. Twelve months after surgery, total weight loss percentage was higher and HbA1c lower in the mRYGB group than in the SG and GCP groups (-35.2 ± 8.1 and 5.1 ± 0.6% vs. -27.8 ± 5.4 and 6.2 ± 0.8% vs. -20.5 ± 6.8 and 6.6 ± 1.3%; p = 0.007 and p < 0.001, respectively). Moreover, GLP-1 AUC at months 1 and 12 was greater and T2D remission was higher in mRYGB (80 vs. 53.3 vs. 20%, p < 0.001). Insulin treatment (odds ratio (OR) 0.025, p = 0.018) and the increase in GLP-1 AUC from baseline to month 1 (OR 1.021, p = 0.013) were associated with T2D remission.. mRYGB achieves a superior rate of weight loss and T2D remission at month 12. Enhanced GLP-1 secretion 1 month after surgery was a determinant of glucose metabolism improvement. Registration number ( http://www.clinicaltrials.gov ): NCT14104758.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Gastroplasty; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Remission Induction; Stomach; Weight Loss

Laparoscopic sleeve gastrectomy is one of the most common techniques in bariatric surgery, but there is no consensus on the optimal distance from the pylorus to start the gastric transection. The aim of this study is to determine the differences in gastric emptying, gastric distension and metabolic response between two starting distances.. This is a prospective randomised study of 60 patients (30 patients with the section at 3 cm and 30 patients at 8 cm from the pylorus). We calculate at 6 and 12 months from surgery gastric emptying by scintigraphy (T1/2 min), gastric volume by CT scan (cc) and metabolic response by blood sample analysis (glucose, HbA1c, insulin, HOMA-IR, GLP-1, GIP and C-peptide).. Gastric emptying increases the speed significantly in both groups but is greater in the 3-cm group (p < 0.05). Dividing groups into type 2 diabetic patients and non-diabetic patients, the speed in non-diabetic patients is significantly higher for the 3-cm group. Residual volume increases significantly in both groups, and there are no differences between them. One year after surgery, there are significant improvements in the hyperinsulinaemia in the patients of the 3-cm group with respect to the 8-cm group, but only in diabetic patients. No differences between groups are found regarding changes in GLP-1 or GIP.. Gastric emptying is faster in patients with antrum resection. The distance does not influence the gastric emptying of diabetic patients. Other mechanisms may explain metabolic response besides GLP-1 and its association with improvements in diabetes via gastric emptying.

Topics: Adult; Aged; C-Peptide; Female; Gastrectomy; Gastric Emptying; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Organ Size; Prospective Studies; Pylorus; Stomach

Roux-en-Y gastric bypass (RYGB) accelerates gastric pouch emptying, enhances postprandial glucagon-like peptide 1 (GLP-1) and insulin, and lowers glucose concentrations. To prevent discomfort and reactive hypoglycemia, it is recommended that post-RYGB patients eat small, frequent meals and avoid caloric drinks. However, the effect of meal size and texture on GLP-1 and metabolic response has not been studied.. To demonstrate that frequent minimeals and solid meals (S) elicit less GLP-1 and insulin release and less reactive hypoglycemia and are better tolerated compared with a single isocaloric liquid meal (L).. A university hospital.. In this prospective study, 32 RYGB candidates were enrolled and randomized to L or S groups before gastric bypass. Each subject received an L or S 600-kcal single meal (SM) administered at hour 0 or three 200-kcal minimeals administered at hours 0, 2, and 4 on 2 separate days. Twenty-one patients were retested 1 year after RYGB. Blood and visual analogue scale measurements were collected up to 6 hours postprandially. Outcome measures included gastric pouch emptying, glucose, insulin, and GLP-1; hunger, fullness, and stomach discomfort were measured by visual analogue scale.. Twenty-one were patients retested after RYGB (L: n = 12; S: n = 9). Meal texture had a significant effect on peak GLP-1 (L-SM: 106.1 ± 67.2 versus S-SM: 45.3 ± 25.2 pM, P = .004), peak insulin, and postprandial glucose. Hypoglycemia was more frequent after the L-SM meal compared with the S-SM. Gastric pouch emptying was 2.4 times faster after RYGB but was not affected by texture.. Meal texture and size have significant impact on tolerance and metabolic response after RYGB.

Topics: Adult; Blood Glucose; Diet; Female; Gastric Bypass; Gastric Emptying; Glucagon-Like Peptide 1; Humans; Insulin; Male; Meals; Obesity, Morbid; Prospective Studies; Young Adult

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Topics: Adult; Appetite Regulation; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Enteroendocrine Cells; Feeding Behavior; Female; Gastrectomy; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Italy; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Time Factors; Weight Loss

The purpose of this study was to evaluate the efficacy and safety of Endobarrier® in grade 1 obese T2DM patients with poor metabolic control and the role of gastro-intestinal hormone changes on the metabolic outcomes.. Twenty-one patients aged 54.1 ± 9.5 years, diabetes duration 14.8 ± 8.5 years, BMI 33.4 ± 1.9 kg/m. Patients lost 14.9 ± 5.7 % of their total body weight. HbA1c decreased 1.3 % in the first month, but at the end of the study, the reduction was 0.6 %. HbA1c ≤ 7 % was achieved in 26.3 % of patients. No differences in GLP-1 AUC values were found before and after implant. Fasting plasma ghrelin and PYY concentrations increased from month 1 to 12. Conversely, fasting plasma glucagon concentrations decreased at month 1 and increased thereafter. Weight (β 0.152) and HbA1c decrease at month 1 (β 0.176) were the only variables predictive of HbA1c values at 12 months (adjusted R. Endobarrier® in T2DM patients with grade I obesity and poor metabolic control is associated with significant weight decrease and moderate reduction in HbA1c at month 12. Our data do not support a role for GLP-1 in the metabolic improvement in this subset of patients.

Topics: Adult; Bariatric Surgery; Blood Glucose; Device Removal; Diabetes Mellitus, Type 2; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Prosthesis Implantation

The purpose of this study was to compare acute changes of non-esterified fatty acids (NEFA) in relation to beta cell function (BCF) and insulin resistance in obese patients with type 2 diabetes (T2D) who underwent laparoscopic gastric bypass (GBP), laparoscopic sleeve gastrectomy (SG) or very low calorie diet (VLCD).. In a non-randomised study, fasting plasma samples were collected from 38 obese patients with T2D, matched for age, body mass index (BMI) and glycaemic control, who underwent GBP (11) or SG (14) or VLCD (13). Samples were collected the day before and 3 days after the intervention, during a 75-g oral glucose tolerance test. Glucose, insulin, c-peptide, glucagon like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) were measured, and individual NEFAs were measured using a triple-quadrupole liquid chromatography-mass spectrometry (LC-MS/MS). BCF by mathematical modelling and insulin resistance were estimated.. Palmitic acid significantly decreased after each intervention. Monounsaturated/polyunsaturated ratio (MUFA/PUFA) and unsaturated/saturated fat ratios increased after each intervention. BCF was improved only after VLCD. Linoleic acid was positively correlated with total insulin secretion (p = 0.03). Glucose sensitivity correlated with palmitic acid (p = 0.01), unsaturated/saturated ratio (p = 0.0008) and MUFA/PUFA (p = 0.009). HOMA-IR correlated with stearic acid (p = 0.03), unsaturated/saturated ratio (p = 0.005) and MUFA/PUFA (p = 0.009). GIP AUC0-120 correlated with stearic acid (p = 0.04), but not GLP-1.. GBP, SG and VLCD have similar acute effects on decreasing palmitic acid. Several NEFAs correlated with BCF parameters and HOMA-IR.

Topics: Adult; Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Type 2; Fatty Acids; Female; Glucagon-Like Peptide 1; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Obesity, Morbid; Tandem Mass Spectrometry; Young Adult

Changes in satiety regulation are known to play a pivotal role in the weight loss effects of Roux-en-Y gastric bypass (RYGB) and the mechanisms by which these changes occur are not entirely known. There are previous reports of the influence of GLP-1 to cause enhancement of satiation, but in regard to GLP-2, it remains unclear. This study aimed to determine whether there is a correlation between the levels of GLP-1 and GLP-2 and satiety regulation following RYGB.. An exploratory prospective cohort study was made which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 levels were determined before and after surgery and correlated with visual analogue scale scores for satiety.. GLP-2 AUC after standard meal tolerance test (MTT) was significantly higher following surgery (945.3 ± 449.1 versus 1787.9 ± 602.7; p = 0.0037). Postoperatively, GLP-1 AUC presented a significant negative correlation with the mean score obtained in the first question of the visual analogue scale ("how hungry do you feel?") (p = 0.008); GLP-2 AUC presented a significant positive correlation with the mean score of the third ("how full do you feel?") question, and a significant positive correlation with the mean score achieved in the fourth question ("how much do you think you can eat?"), (p = 0.005 and p = 0.042, respectively).. GLP-1 and GLP-2 were significantly correlated with satiety assessment within this sample. Further research is necessary to confirm these findings.

Topics: Adolescent; Adult; Aged; Appetite Regulation; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Hunger; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Prospective Studies; Satiation; Weight Loss; Young Adult

To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions.. Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), ß-cell function, hepatic insulin resistance (HIR) and adipose tissue insulin resistance (AT-IR) and insulin sensitivity (IS).. Post treatment, the EXE group showed a significant reduction in body weight ( P < .001). The postmeal time-course of glucose, insulin and ISR showed a lower peak between 60 and 180 minutes in phase with a reduction in RaO ( P < .01). After an initial similar suppression, EGP resumed at higher rates between 60 and 180 minutes ( P = .02) in EXE vs CT, while total RaO and EGP were similar throughout the MTT. In EXE, the postmeal glucagon, GLP1 and GIP responses were reduced ( P < .05). Fasting and postprandial lipolysis and ß-cell function were unaltered by active treatment. HIR, AT-IR and IS were all improved after exenatide treatment ( P < .05).. In morbidly obese non-diabetic subjects, exenatide causes weight loss, decreased postprandial glycaemia and glucagon response without changes in ß-cell function. These effects are consequent upon delayed oral glucose appearance in the circulation. Exenatide treatment is also associated with an improvement in hepatic, adipose tissue and whole-body IS with no influence on postprandial lipolysis.

Topics: Adipose Tissue; Adult; Blood Glucose; Exenatide; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Lipolysis; Liver; Male; Middle Aged; Obesity, Morbid; Peptides; Postprandial Period; Venoms

To evaluate early changes in glycemia, insulin physiology and gut hormone responses to an easily tolerated and slowly ingested solid, low-carbohydrate mixed meal test (MMT) following laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery.. This was a prospective non-randomized study. Plasma glucose, insulin and c-peptide (to estimate hepatic insulin extraction; %HIE), incretins (GIP, aGLP-1) and pancreatic polypeptide (PP) responses to the MMT were measured at 4-8 weeks before and after surgery in obese, metabolically healthy patients (RYGB=10F or LAGB =7F/1M). Supplementary clamp data on basal endogenous glucose production (EGP) and peripheral insulin action (Rd=rate of glucose disposal) and metabolic clearance rates of insulin (MCR-INS) were available in five of the RYGB patients. Repeated measures were appropriately accounted for in the analyses.. RYGB results in distinctly different changes in plasma glucose, insulin and gut hormone response patterns to a solid, slowly ingested low-carbohydrate MMT versus LAGB. Altered nutrient delivery, along with indirect evidence for changes in hepatic and peripheral insulin physiology, are consistent with the greater early improvement in glycemia observed after RYGB versus LAGB surgery.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Carbohydrate-Restricted; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Incretins; Insulin; Male; Meals; Obesity, Morbid; Postoperative Care; Postprandial Period; Prospective Studies; Treatment Outcome; Weight Loss

Both Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) decrease the latency of food delivery to the proximal small intestine. This is implicated in exaggerated post-prandial release of glucagon-like peptide 1 (GLP-1), which provokes early satiety and reductions in food intake. Altered stomach anatomy also creates a deficit in enzymatic pre-processing. The impact of this state effect as a modulator of gut hormone responses remains underexplored.. A double-blind cross-over trial study was conducted in 13 healthy subjects assigned to receive in the fasted state and in random order at 1 week apart, a direct jejunal infusion of either intact casein or a casein hydrolysate. Downstream effects on GLP-1 release, ratings of hunger and fullness and food and water intake on each study day were recorded when an ad libitum meal was provided 30 min after the infusion.. Circulating GLP-1 was increased 25 min after infusions and peaked to a similar degree at 15 min post-meal initiation. The hormone surge had no impact on ratings of hunger and fullness ahead of the ad libitum meal. The kinetic and magnitude of satiation following each infusion was not significantly different. Food and water intake were likewise not differentially impacted by the two infusion types.. Protein macronutrient state upon arrival in the small intestine does not in isolation impact upon GLP-1 responses and subsequent onset of satiety. This potentially points to rate of delivery being the dominant factor in exaggerated post-prandial GLP-1 responses in patients post-RYGB and VSG.

Topics: Adult; Caseins; Cross-Over Studies; Double-Blind Method; Eating; Female; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Intubation, Gastrointestinal; Male; Obesity, Morbid; Reference Values; Satiation

Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

Topics: Adult; Blood Glucose; Catecholamines; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Middle Aged; Obesity, Morbid

Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY. In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY. Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY

Topics: Appetite; Appetite Regulation; Cross-Over Studies; Denmark; Diabetes Mellitus, Type 2; Eating; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Treatment Outcome; Weight Loss

Intestinal glucose absorption is mediated by sodium-dependent glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses.. This study aimed to examine intestinal glucose absorption in morbidly obese humans and its relationship to the expression of STR and glucose transporters, glycemia, and incretin responses.. Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 ± 4 kg/m(2)) and 11 lean controls (BMI, 25 ± 1 kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-minute intraduodenal glucose infusion (30 g glucose and 3 g 3-O-methylglucose [3-OMG]).. Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), insulin, and glucagon were measured over 270 minutes. Expression of duodenal SGLT-1, GLUT2, and STR (T1R2) was quantified by PCR.. The increase in plasma 3-OMG (P < .001) and blood glucose (P < .0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r = 0.78, P < .01). In response to intraduodenal glucose, plasma GIP (P < .001), glucagon (P < .001), and insulin (P < .001) were higher, but GLP-1 (P < .001) was less in the obese compared with lean. Expression of SGLT-1 (P = .035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r = 0.60, P = .01), GIP (r = 0.67, P = .003), and insulin (r = 0.58, P = .02).. In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes.

Topics: 3-O-Methylglucose; Adult; Blood Glucose; Female; Gastric Inhibitory Polypeptide; Gene Expression; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Transport Proteins, Facilitative; Humans; Incretins; Insulin; Intestinal Absorption; Male; Middle Aged; Obesity, Morbid; Time Factors

Bariatric surgery constitutes the most effective treatment for severely obese type 2 diabetic patients. Exenatide is a glucagon-like peptide 1 receptor agonist that can improve glycemic control and cause weight loss in patients with type 2 diabetes. Clinical experience with exenatide in obese patients with type 2 diabetes waiting for bariatric surgery has not been reported. The aim of the study was to evaluate, in clinical practice, weight and metabolic effects of exenatide (after 3 and 6 months) in patients with type 2 diabetes and obesity waiting for bariatric surgery.. A total of 100 diabetic adult subjects with a BMI ≥ 35 kg/m(2) were included. Primary endpoints were changes in weight and HbA1c after 6 months of treatment. Secondary endpoints were changes from baseline of a variety of clinical measures (triglycerides levels, blood pressure, and waist circumference). Data were analyzed at 3 and 6 months of follow-up.. Treatment for 6 months with exenatide decreased significantly body weight (-12.5 kg) and waist circumference (-13 cm). Twenty percent of patients reduced their BMI under 35 kg/m(2) and significantly improved their metabolic profile (HbA1c <7 %). Significant and maintained decreases in HbA1c of 1 % were observed in the 3 and 6 months cohorts. Triglycerides levels and blood pressure also decreased from baseline to the end of the study. Treatment was discontinued in 19 % of patients mainly due to drug inefficacy (6 %) or adverse events (4 %).. Exenatide twice daily (BID) leads to early, robust, and significant weight loss in a subset of patients with diabetes and severe obesity before bariatric surgery. Clinical trials are needed to confirm the benefits of GLP-1 agonists in type 2 diabetic obese patients or high-risk super-obese patients waiting for bariatric surgery.

Topics: Adult; Bariatric Surgery; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Male; Middle Aged; Obesity, Morbid; Peptides; Prospective Studies; Treatment Outcome; Venoms; Waist Circumference; Weight Loss

Gastric bypass surgery (GBP) results in the rapid resolution of type 2 diabetes. Most studies aiming to explain the underlying mechanisms are limited to data obtained after a postsurgical recovery period, making assessment of confounding influences from, for example, weight loss and altered nutrient intake difficult.. To examine the impact of GBP on hormonal and metabolite profiles under conditions of identical nutrient intake independent of weight loss, we studied GBP patients fitted with a gastrostomy tube to enable the administration of nutrients to bypassed segments of the gut. Thus, this model allowed us to simulate partially the preoperative condition and compare this with the postoperative situation in the same patient.. Patients (n = 4) were first given a mixed meal test (MMT) orally and then via the gastrostomy tube, preceded by overnight and 2-hour fasting, respectively. Blood samples were assessed for hormones and metabolites.. The oral MMT yielded 4.6-fold increase in plasma insulin (P < .05), 2-fold in glucagon-like peptide-1 (P < .05), and 2.5-fold in glucose-dependent insulinotropic peptide (P < .05) plasma levels, compared with the gastrostomy MMT. The changes in hormone levels were accompanied by elevated branched-chain amino acid levels (1.4-2-fold, P < .05) and suppressed fatty acid levels (∼50%, P < .05).. These data, comparing identical nutrient delivery, demonstrate markedly higher incretin and insulin responses after oral MMT than after gastric MMT, thereby providing a potential explanation for the rapid remission of type 2 diabetes observed after GBP. The simultaneous increase in branched-chain amino acid questions its role as a marker for insulin resistance.

Topics: Adult; Amino Acids, Branched-Chain; Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrostomy; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Meals; Obesity, Morbid; Postoperative Period; Postprandial Period

Increased delivery of bile acid salts (BA) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery. To further elucidate a potential role of BA in the secretion of GLP-1 and PYY, we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospective, randomized 1-year trial.. Patients received a standard test meal and blood was collected before and after eating, prior to, and 1 week, 3 months, and 12 months after surgery.. Pre-surgery, basal BA concentrations were significantly lower in bariatric patients than in healthy controls. One year post-surgery, bariatric patients expressed variably increased BA concentrations (gastric bypass patients ∼2 fold increase, P ≤ 0.05). However, whereas in both patient groups, marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery, changes in plasma BA followed a different pattern: basal and postprandial plasma BA concentrations increased much slower, more progressively with significant increases only 1-year post-surgery.. Based on these findings, BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients.

Topics: Adult; Bile Acids and Salts; Blood Glucose; Body Mass Index; Body Weight; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Pilot Projects; Postprandial Period; Prospective Studies

Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered.. Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery.. After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon.. After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism.. ClinicalTrials.gov NCT01559779.

Topics: Adult; Blood Glucose; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity, Morbid; Pancreas; Peptide Fragments; Postprandial Period; Treatment Outcome

The long-term results of Roux-en-$\\hbox{Y}$ gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail.. Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery.. Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m(2) for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m(2) for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up.. Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.

Topics: Body Mass Index; Eating; Female; Gastric Bypass; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Reoperation; Weight Loss

The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.. In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).. In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p < 0.012 vs. LRYGB).. Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.

Topics: Adult; Blood Glucose; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Laparoscopy; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), β-cell glucose sensitivity (β-GS), and disposition index (D(β-GS): β-GS × 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 ± 2.3, 1 wk: 7.0 ± 1.2 (P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 ± 3, 1 wk: 8.2 ± 2 (P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. β-GS increased in T2D [Pre: 1.03 ± 0.49, 1 wk: 1.70 ± 1.2, (P = 0.012)] but did not change in NGT. The increase in DI(β-GS) was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved β-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Obesity, Morbid; Postprandial Period; Time Factors

Laparoscopic Roux-en Y-Gastric bypass (LRYGBP) is the commonest available option for the surgical treatment of morbid obesity. Weight loss following bariatric surgery has been linked to changes of gastrointestinal peptides, shown to be implicated also in metabolic effects and appetite control. The purpose of this study was to evaluate whether gastric fundus resection in patients undergoing LRYGBP enhances the efficacy of the procedure in terms of weight loss, glucose levels, and hormonal secretion.. Twelve patients underwent LRYGBP and 12 patients LRYGBP plus gastric fundus resection (LRYGBP+FR). All patients were evaluated before and at 3, 6, and 12 months postoperatively. Blood samples were collected after an overnight fast and 30, 60, and 120 min after a standard 300-kcal mixed meal.. Body weight and body mass index decreased markedly and comparably after both procedures. Fasting ghrelin decreased 3 months after LRYGBP, but increased at 12 months to levels higher than baseline while after LRYGBP+FR was markedly and persistently decreased. Postprandial GLP-1, PYY, and insulin responses were enhanced more and postprandial glucose levels were lower after LRYGBP+FR compared to LRYGBP. Postoperatively, ghrelin changes correlated negatively with GLP-1 changes.. Resection of the gastric fundus in patients undergoing LRYGBP was associated with persistently lower fasting ghrelin levels; higher postprandial PYY, GLP-1, and insulin responses; and lower postprandial glucose levels compared to LRYGBP. These findings suggest that fundus resection in the setting of LRYGBP may be more effective than RYGBP for the management of morbid obesity and diabetes type 2.

Topics: Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Gastric Fundus; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Weight Loss

Altered gut and pancreatic hormone secretion may bolster resolution of insulin resistance after Roux-en-Y gastric bypass (RYGB), but the independent effects of weight loss and hormonal secretion on peripheral glucose disposal are unknown.. Two groups of nondiabetic morbidly obese patients were studied: RYGB followed by standardized caloric restriction (RYGB, n = 12) or caloric restriction alone (diet, n = 10). Metabolic evaluations (euglycemic-hyperinsulinemic clamp, meal tolerance test) were done at baseline and 14 days (both groups) and 6 months after RYGB.. At baseline, body composition, fasting insulin, and glucose and peripheral glucose disposal did not differ between groups. At 14 days, excess weight loss (EWL) was similar (RYGB, 12.7% vs. diet, 10.9%; p = 0.12), fasting insulin and glucose decreased to a similar extent, and RYGB subjects had altered postmeal patterns of gut and pancreatic hormone secretion. However, peripheral glucose uptake (M value) was unchanged in both groups. Six months after RYGB, EWL was 49.7%. The changes in fasting glucose and insulin levels and gut hormone secretion persisted. M values improved significantly, and changes in M values correlated with the % EWL (r = 0.68, p = 0.02).. Improvement in peripheral glucose uptake following RYGB was observed only after substantial weight loss had occurred and correlated with the magnitude of weight lost.

Topics: Adult; Blood Glucose; Body Composition; Caloric Restriction; Fasting; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Weight Loss

Hyperglycemia resolves quickly after bariatric surgery, but the underlying mechanism and the most effective type of surgery remains unclear.. To examine glucose metabolism and beta-cell function in patients with type 2 diabetes mellitus (T2DM) after two types of bariatric intervention; Roux-en-Y gastric bypass (RYGB) and gastric restrictive (GR) surgery.. Prospective, nonrandomized, repeated-measures, 4-week, longitudinal clinical trial.. In all, 16 T2DM patients (9 males and 7 females, 52+/-14 years, 47+/-9 kg m(-2), HbA1c 7.2+/-1.1%) undergoing either RYGB (N=9) or GR (N=7) surgery.. Glucose, insulin secretion, insulin sensitivity at baseline, and 1 and 4 weeks post-surgery, using hyperglycemic clamps and C-peptide modeling kinetics; glucose, insulin secretion and gut-peptide responses to mixed meal tolerance test (MMTT) at baseline and 4 weeks post-surgery.. At 1 week post-surgery, both groups experienced a similar weight loss and reduction in fasting glucose (P<0.01). However, insulin sensitivity increased only after RYGB, (P<0.05). At 4 weeks post-surgery, weight loss remained similar for both groups, but fasting glucose was normalized only after RYGB (95+/-3 mg 100 ml(-1)). Insulin sensitivity improved after RYGB (P<0.01) and did not change with GR, whereas the disposition index remained unchanged after RYGB and increased 30% after GR (P=0.10). The MMTT elicited a robust increase in insulin secretion, glucagon-like peptide-1 (GLP-1) levels and beta-cell sensitivity to glucose only after RYGB (P<0.05).. RYGB provides a more rapid improvement in glucose regulation compared with GR. This improvement is accompanied by enhanced insulin sensitivity and beta-cell responsiveness to glucose, in part because of an incretin effect.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Weight Loss

Many of the metabolic benefits of Roux-en-Y gastric bypass (RYGB) occur before weight loss. In this study we investigated the influence of caloric restriction on the improvements in the metabolic responses that occur within the 1st week after RYGB. RESEARCH METHODS AND DESIGN: A mixed meal was administered to nine subjects before and after RYGB (average 4 +/- 0.5 days) and to nine matched, obese subjects before and after 4 days of the post-RYGB diet.. Weight loss in both groups was minimal; the RYGB subjects lost 1.4 +/- 5.3 kg (P = 0.46) vs. 2.2 +/- 1.0 kg (P = 0.004) in the calorically restricted group. Insulin resistance (homeostasis model assessment of insulin resistance) improved with both RYGB (5.0 +/- 3.1 to 3.3 +/- 2.1; P = 0.03) and caloric restriction (4.8 +/- 4.1 to 3.6 +/- 4.1; P = 0.004). The insulin response to a mixed meal was blunted in both the RYGB and caloric restriction groups (113 +/- 67 to 65 +/- 33 and 85 +/- 59 to 65 +/- 56 nmol x l(-1) x min(-1), respectively; P < 0.05) without a change in the glucose response. Glucagon-like peptide 1 levels increased (9.2 +/- 8.6 to 12.2 +/- 5.5 pg x l(-1) x min(-1); P = 0.04) and peaked higher (45.2 +/- 37.3 to 84.8 +/- 33.0 pg/ml; P = 0.01) in response to a mixed meal after RYGB, but incretin responses were not altered after caloric restriction.. These data suggest that an improvement in insulin resistance in the 1st week after RYGB is primarily due to caloric restriction, and the enhanced incretin response after RYGB does not improve postprandial glucose homeostasis during this time.

Topics: Adipokines; Adult; Blood Glucose; Caloric Restriction; Combined Modality Therapy; Eating; Fasting; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Loss

The exclusion of the proximal small intestine is thought to play a major role in the rapid improvement in the metabolic control of diabetes after gastric bypass.. In this randomized, prospective, parallel group study, we sought to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) with those of laparoscopic sleeve gastrectomy (LSG) on fasting, and meal-stimulated insulin, glucose, and glucagon-like peptide-1 (GLP-1) levels.. Thirteen patients were randomized to LRYGB and 14 patients to LSG. The mostly nondiabetic patients were evaluated before, and 1 week and 3 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before and after food intake in both groups for insulin, GLP-1, glucose, PYY, and ghrelin concentrations. This trial was registered in www.clinicaltrials.gov (NCT00356213) before the first patient was randomized.. Body weight and body mass index decreased markedly (P < 0.002) and comparably after either procedure. Excess BMI loss was similar at 3 months (43.3 +/- 12.1% vs. 39.4 +/- 9.4%, P > 0.36). After surgery, patients had markedly increased postprandial plasma insulin and GLP-1 levels, respectively (P < 0.01) after both of these surgical procedures, which favor improved glucose homeostasis. Compared with LSG, LRYGB patients had early and augmented insulin responses as early as 1-week postoperative; potentially mediating improved early glycemic control. After 3 months, no significant difference was observed with respect to insulin and GLP-1 secretion between the 2 procedures.. Both procedures markedly improved glucose homeostasis: insulin, GLP-1, and PYY levels increased similarly after either procedure. Our results do not support the idea that the proximal small intestine mediates the improvement in glucose homeostasis.

Topics: Adult; Blood Glucose; Body Mass Index; Cohort Studies; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Young Adult

Alterations in entero-endocrine signaling may play a role in improvements in satiety and glucose tolerance after Roux-en-Y gastric bypass (RYGB). We report our findings of gut hormone secretion in a cohort of diabetic and nondiabetic morbidly obese patients.. Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: 5 were diabetic and 9 were female. Nonfasting plasma levels of glucagon-like peptide-1 (GLP-1), insulin, desacyl ghrelin, active ghrelin, neuropeptide Y (NPY), and gastric inhibitory polypeptide (GIP) were determined preoperatively and 6 months postoperatively.. Mean patient age was 42 +/- 11 years, and the mean preoperative body mass index was 50 +/- 6 kg/m(2). At 6 months mean BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In non-diabetics, compared to preoperative levels, there were significant increases in GLP-1 and desacyl-ghrelin in the nondiabetic patients (P = 0.046 and P = 0.016, respectively); no change in plasma insulin, active ghrelin, NPY, or GIP was demonstrated. In contrast, when compared to preoperative levels, there were no significant changes in entero-endocrine hormone levels in the diabetic cohort postoperatively.. At 6 months postoperation, RYGB significantly alters the hormone levels for GLP-1 and desacyl-ghrelin in morbidly obese nondiabetic patients. No significant change was noted in a matched cohort of diabetic patients. Weight loss was similar in diabetics and nondiabetics, suggesting that GLP-1 and ghrelin are not the only mechanisms producing weight loss after RYGB.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Neuropeptide Y; Obesity, Morbid; Peptide Hormones; Weight Loss

To evaluate the physiologic importance of the satiety gut hormones.. Controversy surrounds the physiologic role of gut hormones in the control of appetite. Bariatric surgery remains the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass.. We correlated peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) changes within the first week after gastric bypass with changes in appetite. We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass. Finally, we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake.. Postprandial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass (P < 0.05). Changes in appetite are evident within days after gastric bypass surgery (P < 0.05), and unlike other operations, the reduced appetite continues. However, in patients with poor weight loss after gastric bypass associated with increased appetite, the postprandial PYY and GLP-1 responses are attenuated compared with patients with good weight loss (P < 0.05). Inhibiting gut hormone responses, including PYY and GLP-1 after gastric bypass, results in return of appetite and increased food intake (P < 0.05).. The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations, and appetite returns when the release of gut hormones is inhibited. The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implications for the treatment of obesity.

Topics: Appetite Regulation; Body Mass Index; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric emptying and the contribution of this peptide in the regulation of food intake as a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for rapid inactivation of the circulating peptide, in morbidly obese patients, before and after weight loss resulting from biliopancreatic diversion.. Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 +/- 1.8) and 9 age-matched healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV activity. The patients repeated the test meal after 50 % overweight reduction resulting from surgical treatment (BMI = 33.8 +/- 1.1).. While nutrient ingestion significantly increased plasma GLP-1 levels in the control group (30', 60': p < 0.01), the test-meal failed to modify basal peptide values in the obese patients, and an overall reduction in circulating GLP-1 occurred during the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted as being significantly higher than controls, both at fasting and in response to the meal (p < 0.05). With respect to preoperative values, an overall increase in circulating GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001). Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even after considerable weight loss (p < 0.05 vs. controls).. First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, the defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities; Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree, the increase in postoperative GLP-1 levels mainly resulting from hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed, selective DPP-IV inhibitors could actually represent an ideal approach to obesity management.

Topics: Adult; Biliopancreatic Diversion; Dipeptidyl Peptidase 4; Eating; Female; Glucagon; Glucagon-Like Peptide 1; Humans; Male; Obesity, Morbid; Peptide Fragments; Postoperative Period; Protein Precursors; Weight Loss

The aim of this study was to compare changes in gastrointestinal hormones and appetite ratings after a similar weight loss induced by a very low-energy diet alone or in combination with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).. Patients with severe obesity scheduled for SG (n = 15) and RYGB (n = 14) and 15 controls (very low-energy diet alone) were recruited. Body weight/composition, plasma concentrations of ß-hydroxybutyric acid, acylated ghrelin, total glucagon-like peptide-1, total peptide YY, cholecystokinin, and ratings of hunger, fullness, desire to eat, and prospective food consumption were measured pre- and postprandially, before and after 10 weeks of intervention.. Changes in body weight/composition and level of ketosis were similar across groups. In SG and RYGB, basal and postprandial acylated ghrelin declined, and postprandial glucagon-like peptide-1 increased, both significantly more compared with controls. Postprandial peptide YY increased in all groups. Overall, postprandial hunger decreased, and postprandial fullness increased. But ratings of desire to eat and prospective food consumption were more favorable after both surgeries compared with controls.. Weight loss with SG and RYGB leads to more favorable changes in gastrointestinal hormones compared with diet alone, although ratings of appetite were reduced across all groups.

Topics: Appetite; Diet; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Weight Loss

Sleeve gastrectomy with transit bipartition (SG-TB) could be an attractive alternative to Roux-en-Y gastric bypass (RYGB) on weight loss and improvement of comorbidities in patients with obesity. However, there is little long-term data. Translational research on a rat model could allow long-term projection to assess efficacy and safety of SG-TB. The aim of this research was to evaluate the long-term efficacy and safety of SG-TB compared to RYGB and SHAM in rat model.. Ninety-four male obese Wistar rats were distributed into 3 groups: SG-TB (n = 34), RYGB (n = 32), and SHAM (control group, n = 28). The percentage of total weight loss (%TWL), coprocalorimetry, glucose and insulin tolerance test, insulin, GLP-1, PYY, and GIP before and after surgery were assessed. The animals were followed over 6 months (equivalent to 16 years in humans).. At 6 months, %TWL was significantly greater(p = 0.025) in the SG-TB group compared to the RYGB group. There was no difference between the groups (p = 0.86) in malabsorption 15 and 120 days postoperatively. Glucose tolerance was significantly improved (p = 0.03) in the SG-TB and RYGB groups compared to the preoperative state. Insulin secretion, at 3 months, was significantly more important in the SG-TB group (p = 0.0003), compared to the RYGB and SHAM groups. GLP-1 secretion was significantly increased in the SG-TB and RYGB groups compared to the preoperative state (p = 0.001) but similar between SG-TB and RYGB animals (p = 0.72).. In a rat model, at long term compared to RYGB, SG-TB provides greater and better-maintained weight loss and an increased insulin secretion without impairing nutritional status.

Topics: Animals; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Male; Nutritional Status; Obesity; Obesity, Morbid; Rats; Rats, Wistar; Retrospective Studies; Treatment Outcome; Weight Loss

One-anastomosis gastric bypass (OAGB) is as effective as Roux-en-Y gastric bypass (RYGB) regarding weight loss and diabetes remission. However, there are no data on gut hormone secretions after OAGB. The aim of this study was to compare fasting and postprandial secretions of gut and pancreatic hormones in OAGB versus RYGB patients.. Twenty-nine patients, 16 OAGB- and 13 RYGB-operated, underwent a liquid mixed-meal tolerance test at 2 years' post-surgery. Blood was sampled before and 15, 30, 60, 90, and 120 min after meal for plasma measurement of glucose, C-peptide, insulin, glucagon, GLP-1, GIP, GLP-2, PYY, and ghrelin.. Percentage of total weight loss 2 years post-surgery were -33.9 ± 1.8% for OAGB and -31.2 ± 1.6% for RYGB (p = 0.6). Four patients with persistent diabetes were excluded for further analysis. Fasting and postprandial glucose levels (peaks and area under curve values) were similar between groups. HOMA index was lower in the OAGB group (0.8 ± 0.1 vs 1.3 ± 0.2 in RYGB, p < 0.05). Levels of C-peptide (or insulin) measured at 30 min were significantly lower in OAGB vs RYGB patients (6.9 ± 0.5 vs 9.7 ± 1.1 µg/l, p < 0.05). No difference was observed between OAGB and RYGB groups for GLP-1, GLP-2, PYY, or ghrelin postprandial secretions, but GIP tended to be lower in OAGB vs RYGB patients (756 ± 155 vs 1100 ± 188 pg/ml for postprandial peak concentrations, p = 0.06).. This is the first clinical study showing that OAGB procedure, like RYGB, results in high postprandial secretions of gut hormones, in particular GLP-1.. Clinical Trials NCT03482895.

Topics: Anastomosis, Roux-en-Y; Blood Glucose; C-Peptide; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Obesity, Morbid; Pilot Projects; Weight Loss

The mechanism underlying postprandial glucagon-like peptide-1 (GLP-1) changes after metabolic surgery remains mostly unclarified. This investigation aimed to address whether the vagus nerve-spleen anti-inflammatory axis is involved in the rise in postprandial GLP-1 levels in type 2 diabetes mellitus (T2DM) rats following metabolic surgery.. T2DM rat model was established with a high-fat diet and a low dose of streptozotocin and subjected to Roux-en-Y gastric bypass (RYGB) and splenic denervation. A mixed-meal tolerance test for postprandial GLP-1 response was performed. TNF-α in the plasma, spleen, and ileum was measured by ELISA, and alpha 7 nicotinic acetylcholine receptor (α7nAChR) expression in the spleen was analyzed by Western blot.. Postprandial GLP-1 improvement by RYGB was accompanied by the reduction of TNF-α levels in spleen and ileum and up-regulation of splenic α7nAChR in T2DM rats. Splenic denervation abrogates a rise in postprandial GLP-1 levels in response to the mixed-meal challenge, along with higher TNF-α levels in spleen and ileum and down-regulation of splenicα7nAChR, compared with denervated sham rats.. Our results reveal that the vagus nerve-spleen anti-inflammatory axis mediates the rise of postprandial GLP-1 response after RYGB through lowering TNF-α contents in the intestinal tissue in T2DM rats.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Anti-Inflammatory Agents; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Obesity, Morbid; Rats; Spleen; Tumor Necrosis Factor-alpha; Vagus Nerve

Single anastomosis duodeno-ileostomy with sleeve gastrectomy (SADI-S) is a powerful form of bariatric surgery; however, it has a high risk of malnutrition. Single anastomosis sleeve ileal (SASI) bypass with sleeve gastrectomy may be used as an alternative procedure to avoid malnutrition associated with SADI-S; however, no comparison between the two procedures has been performed.. Sprague-Dawley rats with diabetes (n = 32) were divided into four groups: SADI-S (n = 8), SASI (n = 8), SG (n = 8), and SHAM (n = 8). Body weight, food intake, and fasting blood glucose were measured, and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed before and after surgery. Blood samples were collected before and after the surgery to assess the levels of glucagon-like peptide-1 (GLP-1), hemoglobin, albumin, vitamin B12, calcium, and iron.. The SADI-S and SASI groups showed significantly greater weight loss and better glucose control than the SG group postoperatively. The SADI-S and SASI groups showed similar improvements in glucose control throughout the study. The SADI-S and SASI groups had significantly higher GLP-1 levels than the SG group at 6 months. The SADI-S and SASI groups presented with various degrees of deficiencies, with the SADI-S group showing a higher risk for hypoalbuminemia and iron deficiency than the SASI group.. The SASI procedure may be a better alternative as it has excellent bariatric and metabolic results with lower risk for hypoalbuminemia and can be easily converted into either SADI-S or SG procedures. Nevertheless, further clinical results are needed.

Topics: Anastomosis, Surgical; Animals; Blood Glucose; Diabetes Mellitus; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoalbuminemia; Malnutrition; Obesity, Morbid; Rats; Rats, Sprague-Dawley; Retrospective Studies; Rodentia

The protective effect of transit bipartition against esophagitis has not yet been proven. Thus, we investigate and compare the bariatric outcomes and esophagus' histological changes of sleeve gastrectomy (SG), SG with transit bipartition (SG-TB), and the proximal SG-TB (SG-PTB) in a rodent model.. This study included 45 diabetic Sprague-Dawley rats assigned to one of the four groups, SG-PTB (n = 15), SG-TB (n = 12), SG (n = 10), and SHAM (n = 8). Eight surviving rats from each group were included for further investigation. Histological analysis of the gastroesophageal junction was performed. Body weight, food intake, glucose control, and hormonal changes (glucagon-like peptide-1 and insulin) were assessed before and after surgery in all groups.. Preoperatively, no significant differences were observed in food intake, body weight, and fasting blood glucose levels among the groups. Postoperatively, the SG-PTB and SG-TB groups showed significantly superior glucose control compared to the SG group following the gavage of glucose (p < 0.05). Postoperatively, the SG-PTB and SG-TB groups had higher postoperative GLP-1 levels than postoperative SG and SHAM groups. More severe esophageal hyperpapillomatosis (EHP) of the esophageal section was observed in the SG group. The mucosal height of the SG group was significantly higher than that of the SG-PTB, SG-TB, and SHAM groups (p < 0.05).. The transit bipartition procedure may protect the distal esophagus from histological changes associated with esophagitis. Clinical studies are needed to confirm the anti-reflux effects of transit bipartition.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Esophagitis; Gastrectomy; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Rats; Rats, Sprague-Dawley; Rodentia

Roux-en-Y gastric bypass (RYGB) surgery produces significant weight loss. However, a number of patients experience weight regain years after surgery. Factors driving weight regain after surgical interventions are currently being explored. Our objective was to investigate appetite-related measures associated with weight regain after RYGB surgery.. Using a cross-sectional design, 29 participants (49.6 ± 9.1 years of age; current BMI 32.4 ± 4.7 kg/m. Dietary restraint was significantly higher than clinical cutoffs in WM and LWR (p < 0.05). As expected, significant time effects were noted for ghrelin, PYY, and GLP-1, but there were no group differences.. The results suggest that appetite-related outcomes are similar across individuals who have maintained weight loss and experienced regain following RYGB.

Topics: Appetite; Body Weight Maintenance; Cross-Sectional Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Weight Gain; Weight Loss

Exaggerated postprandial incretin and insulin responses are well documented in postbariatric surgery hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). However, less is known about PBH after sleeve gastrectomy (SG).. We sought to compare meal-stimulated hormonal response in those with PBH after SG vs RYGB.. We enrolled 23 post-SG (12 with and 11 without PBH) and 20 post-RYGB (7 with and 13 without PBH) individuals who underwent bariatric surgery at our institution. PBH was defined as plasma glucose less than 60 mg/dL on 4-hour mixed-meal tolerance test (MTT). Islet and incretin hormones were compared across the 4 groups.. Participants (N = 43) were on average 5 years post surgery, with a mean age of 48 years, mean preoperative body mass index of 48.4, 81% female, 61% White, and 53% post SG. Regardless of PBH, the SG group showed lower glucose, glucagon, and glucagon-like peptide 1 (GLP-1) responses to MTT and similar insulin and glucose-dependent insulinotropic polypeptide (GIP) responses compared to the RYGB group. Among those with PBH, the SG group following the MTT showed a lower peak glucose (P = .02), a similar peak insulin (90.3 mU/L vs 171mU/L; P = .18), lower glucagon (P < .01), early GLP-1 response (AUC0-60 min; P = .01), and slower time to peak GIP (P = .02) compared to PBH after RYGB.. Among individuals with PBH, those who underwent SG were significantly different compared to RYGB in meal-stimulated hormonal responses, including lower glucagon and GLP-1 responses, but similar insulin and GIP responses. Future studies are needed to better understand the differential contribution of insulin and non-insulin-mediated mechanisms behind PBH after SG vs RYGB.

Topics: Blood Glucose; Female; Gastrectomy; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Hypoglycemia; Incretins; Insulin; Male; Middle Aged; Obesity, Morbid

Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated.. Significant increases in GLP-1 and PYY. Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.

Topics: Bariatric Surgery; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Pilot Projects; Sugars; Taste; Weight Loss

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.. We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.. RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.. The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose; Hypertrophy; Insulins; Obesity, Morbid; Rats

Performing the Roux-en-Y gastric bypass (RYGBP) in obese Yucatan minipigs provides an opportunity to explore the mechanisms behind the effects of this surgery in controlled environmental and nutritional conditions. We hypothesized that RYGBP in these minipigs would induce changes at multiple levels, as in obese humans. We sought to characterize RYGBP in a diet-induced obese minipig model, compared with a pair-fed sham group. After inducing obesity with an ad libitum high-fat/high-sugar diet, we performed RYGBP (n = 7) or sham surgery (n = 6). Oral glucose tolerance tests (OGTT) were performed before and after surgery. Histological analyses were conducted to compare the alimentary limb at sacrifice with tissue sampled during RYGBP surgery. One death occurred in the RYGBP group at postoperative day (POD) 3. Before sacrifice, weight loss was the same across groups. GLP-1 secretion (OGTT) was significantly higher at 15, 30 and 60 min at POD 7, and at 30 and 60 min at POD 30 in the RYGBP group. Incremental insulin area under the curve increased significantly after RYGBP (p = 0.02). RYGBP induced extensive remodeling of the alimentary limb. Results show that RYGBP can be safely performed in obese minipigs, and changes mimic those observed in humans.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Obesity, Morbid; Pilot Projects; Swine; Swine, Miniature; Treatment Outcome

Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and results in rapid remission of type 2 diabetes (T2D), before significant weight loss occurs. The underlying mechanisms for T2D remission are not fully understood. To gain insight into these mechanisms we used RYGB-operated diabetic GK-rats and Wistar control rats. Twelve adult male Wistar- and twelve adult male GK-rats were subjected to RYGB- or sham-operation. Oral glucose tolerance tests (OGTT) were performed six weeks after surgery. RYGB normalized fasting glucose levels in GK-rats, without affecting fasting insulin levels. In both rat strains, RYGB caused increased postprandial responses in glucose, GLP-1, and GIP. RYGB caused elevated postprandial insulin secretion in Wistar-rats, but had no effect on insulin secretion in GK-rats. In agreement with this, RYGB improved HOMA-IR in GK-rats, but had no effect on HOMA-β. RYGB-operated GK-rats had an increased number of GIP receptor and GLP-1 receptor immunoreactive islet cells, but RYGB had no major effect on beta or alpha cell mass. Furthermore, in RYGB-operated GK-rats, increased Slc5a1, Pck2 and Pfkfb1 and reduced Fasn hepatic mRNA expression was observed. In summary, our data shows that RYGB induces T2D remission and enhanced postprandial incretin hormone secretion in GK-rats, without affecting insulin secretion or beta cell mass. Thus our data question the dogmatic view of how T2D remission is achieved and instead point at improved insulin sensitivity as the main mechanism of remission.

Topics: Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Obesity, Morbid; Rats; Rats, Wistar; Weight Loss

We investigated whether oleic acid (OA), one of the main components of the Mediterranean diet, participates in the regulation of the intestinal circadian rhythm in patients with morbid obesity.. Stomach and jejunum explants from patients with morbid obesity were incubated with oleic acid to analyze the regulation of clock genes.. Stomach explants showed an altered circadian rhythm in CLOCK, BMAL1, REVERBα, CRY1, and CRY2, and an absence in PER1, PER2, PER3 and ghrelin (p > 0.05). OA led to the emergence of rhythmicity in PER1, PER2, PER3 and ghrelin (p < 0.05). Jejunum explants showed an altered circadian rhythm in CLOCK, BMAL1, PER1 and PER3, and an absence in PER2, REVERBα, CRY1, CRY2 and GLP1 (p > 0.05). OA led to the emergence of rhythmicity in PER2, REVERBα, CRY1 and GLP1 (p < 0.05), but not in CRY2 (p > 0.05). OA restored the rhythmicity of acrophase and increased the amplitude for most of the genes studied in stomach and jejunum explants. OA placed PER1, PER2, PER3, REVERBα, CRY1 and CRY2 in antiphase with regard to CLOCK and BMAL1.. There is an alteration in circadian rhythm in stomach and jejunum explants in morbid obesity. OA restored the rhythmicity of the genes related with circadian rhythm, ghrelin and GLP1, although with slight differences between tissues, which could determine a different behaviour of the explants from jejunum and stomach in obesity.

Topics: Adult; Circadian Rhythm; CLOCK Proteins; Female; Gastrectomy; Gastric Bypass; Gene Expression Regulation; Ghrelin; Glucagon-Like Peptide 1; Humans; Jejunum; Male; Middle Aged; Obesity, Morbid; Oleic Acid; Postoperative Period; Stomach

Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied.. We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control.. The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm. We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.

Topics: Animals; Blood Glucose; Gastrectomy; Glucagon; Glucagon-Like Peptide 1; Insulin; Jejunum; Obesity, Morbid; Rats; Rats, Wistar

Early dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention.. Eleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks, and pasireotide 300 μg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period.. During the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4 bpm, p < 0.0001) within 30 min after meal intake, while hypoglycemia occurred in the later postprandial period. The HR increase was accompanied by significant increases in serum albumin, plasma norepinephrine, blood glucose, serum insulin, and plasma GLP-1 concentrations. The postprandial HR changes were positively correlated with the changes in insulin and GLP-1 concentrations. Treatment with acarbose and pasireotide both reduced HR, plasma norepinephrine, and serum insulin, and pasireotide also decreased plasma GLP-1.. RYGB-operated individuals with PBH also have large early postprandial HR increases, hemoconcentration, and sympathetic activation, consistent with early dumping. Moreover, hormone excursions associated with PBH appear to be related to measures of early dumping, suggesting a causal relationship between early dumping and PBH.. NCT02527993.

Topics: Blood Glucose; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Insulin; Obesity, Morbid; Postprandial Period

Bariatric surgery is known to attenuate glomerular hyperfiltration over the long term and thereby protect the kidney from mechanical damage. Whether this effect is directly related to weight loss or is independent of weight as are some of its other beneficial metabolic effects is not known. We explored this question in a preliminary study that directly measured glomerular filtration rate (GFR) before, immediately after, and again many months after Roux-en-Y gastric bypass after large weight loss had occurred. We simultaneously measured stimulated circulating glucagon-like peptide-1, which is upregulated after Roux-en-Y gastric bypass and is a putative mediator of GFR after bariatric surgery. We found no weight-independent effect of Roux-en-Y gastric bypass on GFR nor an association between circulating GLP-1 levels and GFR. These findings, if confirmed in larger studies, will help steer future enquiries in this area.

Topics: Biomarkers; Body Mass Index; Female; Gastric Bypass; Glomerular Filtration Rate; Glucagon-Like Peptide 1; Humans; Kidney; Middle Aged; Obesity, Morbid; Weight Loss

Endoscopic bariatric and metabolic therapies can potentially reproduce similar gastric and small intestinal anatomic and physiologic manipulations as Roux-en-Y gastric bypass. This proof of concept animal study was aimed to assess the feasibility, safety, efficacy, and impact on gastrointestinal physiology of combined intragastric balloons (IGB) and duodenal-jejunal bypass liner (DJBL) for the treatment of obesity.. Five Ossabaw pigs were fed a high-calorie diet to develop obesity and were randomly assigned to receive IGB or DJBL in sequence. The weight gain rate was calculated. Fasting and postprandial blood samples were drawn before any intervention (serving as the baseline group) and 1 month after second device insertion (serving as the combination group) to measure gut neurohormonal changes and metabolic parameters.. Four pigs successfully received a sequential device insertion. One pig developed duodenal sleeve prolapse that was spontaneously resolved. One pig was early terminated because of developing a central line infection. The rate of weight gain in the combination group (0.63 ± 1.3 kg/wk) was significantly lower than the baseline group (1.96 ± 2.17 kg/wk) and numerically lower than after insertion of the IGB (1.00 ± 1.40 kg/wk) or the DJBL (0.75 ± 2.27 kg/wk) alone. A trend of higher postprandial glucagon-like peptide-1 was observed in the combination group compared with the baseline group.. A combination of IGB and DJBL is feasible and well tolerated. A strategy of sequential use of these devices might offer a synergistic approach that can enhance weight loss and metabolic outcomes.

Topics: Anastomosis, Roux-en-Y; Animals; Bariatric Surgery; Combined Modality Therapy; Diet, Atherogenic; Diet, High-Fat; Disease Models, Animal; Duodenum; Feasibility Studies; Gastric Balloon; Glucagon-Like Peptide 1; Jejunum; Obesity, Morbid; Postprandial Period; Proof of Concept Study; Swine; Swine, Miniature; Weight Loss

Roux-en-Y gastric bypass (RYGB) modifies various aspects of eating behavior in morbidly obese individuals to cause marked and lasting weight loss and improvements in metabolic health, but the underlying mechanisms remain poorly understood.. To assess the relative contributions of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY. University hospital, Würzburg, Germany.. HF diet-induced obese male Wistar rats underwent RYGB (n = 11) or sham (n = 7) surgeries and were subsequently maintained on a choice of low-fat (10% calories from fat) and HF (60% calories from fat) diets. From postoperative weeks 4 to 6, acute feeding studies were performed in which the selective GLP-1 receptor antagonist exendin-9 (30 μg/kg), the second-generation selective Y2 receptor antagonist JNJ-31020028 (10 mg/kg), or a combination of both drugs was administered intraperitoneally.. During the observational period weight, adiposity and total food intake were lower while postprandial plasma GLP-1 and peptide tyrosine tyrosine levels were higher for RYGB-operated compared with sham-operated rats. There was a gradual shift in preference from HF to low-fat food in RYGB-operated rats by postoperative week 3. Single antagonist treatments had a relatively modest impact on HF food preference in rats from both surgical groups. However, dual antagonist treatment caused a striking increase in HF food preference specifically in RYGB-operated rats.. GLP-1 and peptide tyrosine tyrosine 3-36 reduce HF food preference additively after RYGB supporting the use of gut hormone combination strategies for healthier feeding behavior.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Feeding Behavior; Food Preferences; Gastric Bypass; Glucagon-Like Peptide 1; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Rats; Rats, Wistar

Gastric bypass with a proximal gastric pouch (Roux-en-Y gastric bypass) induces early diabetes remission. The effect of gastric bypass with a distal gastric pouch remains unknown.. To observe the effect on glucose tolerance and diabetes remission of gastric bypass with a distal gastric pouch.. A type 2 diabetes (T2D) model was created in 44 Sprague-Dawley (SD) rats that randomly underwent Roux-en-Y gastric bypass (RYGB, n = 8); gastric bypass with duodenal-jejunal transit (GB-DJT, n = 8); distal-pouch gastric bypass with duodenal-jejunal transit (DPGB-DJT, n = 8); distal-pouch gastric bypass with duodenal-jejunal bypass (DPGB-DJB, n = 8); sham (n = 6); and Roux-en-Y gastric bypass with esophageal re-anastomosis (RYGB-Er, n = 6) surgery. In the DPGB-DJT and the DPGB-DJB groups, the gastric pouch was created in the distal stomach. In the RYGB and the GB-DJT groups, the gastric pouch was created in the proximal stomach. An oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and mixed-meal tolerance test (MMTT) conducted preoperatively were repeated postoperatively.. GLP-1 AUC recorded preoperatively was significantly increased 8 weeks postoperatively in the RYGB, GB-DJT, and DPGB-DJB groups. Increased GLP-1 AUC in the DPGB-DJT did not reach statistical significance. Improved glucose tolerance in the RYGB and GB-DJT groups was significantly higher than DPGB-DJT group. DPGB-DJB did not improve glucose tolerance significantly. Gastrin level was increased significantly in the DPGB-DJT and DPGB-DJB groups.. In gastric bypass, creating the gastric pouch in the distal region of the stomach significantly impairs the glucose tolerance and diabetes remission in spite of the increased GLP-1 and insulin responses in T2D SD rat model, suggesting that bypassing the distal stomach may be the key mediator of early diabetes remission after RYGB.

Topics: Analysis of Variance; Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Insulin; Insulin Resistance; Male; Obesity, Morbid; Rats; Rats, Sprague-Dawley; Remission Induction

Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB.. Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics.. The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean + SEM, 1094 ± 141 vs. 428 ± 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 ± 70 vs. 103 ± 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH.. Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.

Topics: Adult; Bariatric Surgery; Blood Glucose; Blood Proteins; Case-Control Studies; Female; Fibroblast Growth Factors; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Male; Meals; Middle Aged; Obesity, Morbid; Peptide Fragments; Postoperative Complications; Proteome; Proteomics; Up-Regulation

After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).. To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut.. Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark.. Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes.. Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB.. The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry.. Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon.. Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

Topics: Adolescent; Adult; Balloon Enteroscopy; Biomarkers; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Intestines; Male; Meals; Middle Aged; Obesity, Morbid; Postprandial Period; Prognosis; Prospective Studies; Young Adult

This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls.. This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers. C-reactive protein (CRP) levels and the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 curves were assessed and compared.. The pre-RYGB group presented significantly higher levels of CRP than the post-RYGB (p = 0.001) and the control group (p = 0.001). The inactive CD group presented a higher post-prandial GLP-1 area under the curve (AUC) than the pre-RYGB group (p = 0.009). The post-RYGB group presented significantly higher AUCs of GLP-2 than the pre-RYGB group (p < 0.0001), both inactive and active CD groups (p < 0.0001 in both situations), and the control group (p = 0.002). The pre-RYGB group presented a significantly higher AUC of glucose than the post-RYGB (p = 0.02) and both active and inactive CD groups (p = 0.019 and p = 0.046, respectively). The pre-RYGB group presented a significantly higher AUC of insulin than the control (p = 0.005) and both CD groups (p < 0.0001).. Obesity is associated with an inflammatory state comparable to the one observed in CD; inflammation may also be enrolled in the blockade of GLP-2. CD individuals present a more incretin-driven pattern of glucose metabolism, as a way to prevent hypoglycemia and compensate the carbohydrate malabsorption and GLP-2 blockade.

Topics: Adult; Bariatric Surgery; Blood Glucose; Case-Control Studies; Crohn Disease; Cross-Sectional Studies; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Postprandial Period; Preoperative Period; Young Adult

Topics: Bariatric Surgery; Cognitive Behavioral Therapy; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Feeding Behavior; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Obesity, Morbid; Patient Compliance; Postoperative Complications; Recurrence; Reoperation; Risk Factors; Treatment Failure; Weight Gain

There is an ongoing debate on which procedure provides the best treatment for type 2 diabetes. Furthermore, the pathomechanisms of diabetes improvement of partly anatomically differing operations is not fully understood.. A loop duodenojejunostomy (DJOS) with exclusion of one third of intestinal length, a sleeve gastrectomy (SG), or a combination of DJOS + SG was performed in 8-week-old male ZDF rats. One, three, and six months after surgery, an oral glucose tolerance test and measurements of GLP-1, GIP, insulin, and bile acids were conducted.. After an initial (4 weeks) equal glucose control, DJOS and DJOS + SG showed significantly lower glucose levels than SG 3 and 6 months after surgery. There was sharp decline of insulin levels in SG animals over time, whereas insulin levels in DJOS and DJOS + SG were preserved. GIP levels were significantly larger in both groups containing a sleeve at all three time points, whereas GLP-1 was equal in all groups at all time. Bile acid levels were significantly higher in the DJOS compared to the SG group at all time points. Interestingly, the additional SG in the DJOS + SG group led to lower bile acid levels 1 and 6 months postoperatively.. The effect of SG on glucose control was transient, whereas a duodenal exclusion was the more effective procedure in this model due to a sustained pancreatic function with a preserved insulin secretion.

Topics: Anastomosis, Surgical; Animals; Bariatric Surgery; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Duodenum; Gastrectomy; Glucagon-Like Peptide 1; Glucose Tolerance Test; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Jejunum; Male; Obesity, Morbid; Rats; Rats, Zucker

Weight loss (WL) and altered gut hormonal levels are involved in glucose homeostasis after laparoscopic sleeve gastrectomy (LSG).. The aim of this study was to evaluate the time-related effects of WL, ghrelin, and glucacon-like peptide-1 (GLP-1) plasma concentrations on type 2 diabetes resolution after LSG.. University hospital, Italy.. Ninety-one patients who underwent LSG were investigated. Insulin secretion (insulinogenic index [IGI]), insulin resistance, plasma glucose level and percentage glycated hemoglobin using the oral glucose tolerance test were assessed before surgery, on postoperative day 3, and then at 6, 12, 24, and 36 months after LSG. At the same time points, WL, ghrelin, and GLP-1 levels were determined.. During follow-up, the resolution rate of type 2 diabetes was 9.4%, 42.3%, 71.8%, 81.2%, and 91.8%, respectively. Ghrelin plasma concentrations decreased significantly after LSG (271.5 ± 24.5 pg/mL versus 122.4 ± 23.4 pg/mL, P = .04). GLP-1 plasma concentrations increased significantly after LSG (1.7 ± 2.6 pg/mL versus 2.5 ± 3.4 pg/mL, P = .04). The percentage of excess weight loss and IGI presented a positive linear correlation (r) at all follow-up time points with a strong positive correlation at 12 and 24 months. A strong negative correlation between ghrelin and IGI was recorded during the first 3 days after LSG (r = -.9). GLP-1 and IGI presented a strong positive correlation at day 3 and 6 months (i.e., .8 and .8, respectively).. LSG may affect glucose homeostasis by 2 different time-related modes: a first step in which the hormonal changes play a predominant role in glucose homeostasis and a second step in which the percentage excess weight loss determines the metabolic results.

Topics: Adult; Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Weight Loss; Young Adult

The impact of lifestyle-induced weight loss (WL) on appetite in patients with obesity remains controversial. This study aimed to assess the short- and long-term impact of WL achieved by diet and exercise on appetite in patients with obesity. Thirty-five (22 females) adults with severe obesity (body mass index: 42.5 ± 5.0 kg/m

Topics: Adult; Anaerobic Threshold; Appetite Regulation; Body Mass Index; Diet, Reducing; Exercise; Female; Glucagon-Like Peptide 1; Humans; Hunger; Life Style; Male; Middle Aged; Obesity; Obesity, Morbid; Patient Care Team; Peptide YY; Weight Loss

To find out the best location for intestinal electrical stimulation (IES) to decrease hyperglycemia, and mechanisms involving intraluminal nutrients and plasma glucagon-like peptide-1 (GLP-1) MATERIALS AND METHODS: Eight rats had electrodes implanted at the duodenum and ileums for IES. The oral glucose tolerance test (OGTT) was performed with IES and sham-IES and with/without GLP-1 antagonist, exendin. To study the role of intraluminal nutrients, the experiment was repeated using intraperitoneal glucose tolerance test (IPGTT). Glucagon was administrated in the OGTT/IPGTT to induce temporary hyperglycemia.. (1) In the OGTT, IES at the duodenum reduced blood glucose from 30 to 120 min after oral glucose (P < 0.05, vs. sham-IES) and the hypoglycemic effect was more potent than IES at the ileum. (2) The hypoglycemic effect of IES was absent in IPGTT experiment, suggesting the important role of intraluminal nutrients. (3) An increase in GLP-1 was noted in the OGTT with IES at the duodenum in comparison with sham-IES. Moreover, the blocking effect of exendin suggested the role of GLP-1 in the hypoglycemic effect of IES.. The best stimulation location for IES to decrease hyperglycemia is in the duodenum. The hypoglycemic effect of IES is attributed to the enhancement in nutrient-stimulated release of GLP-1.

Topics: Animals; Blood Glucose; Electric Stimulation; Glucagon-Like Peptide 1; Glucose Tolerance Test; Hyperglycemia; Intestinal Mucosa; Intestines; Male; Nutrients; Obesity, Morbid; Rats; Rats, Sprague-Dawley

Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses. The weight loss is due to loss of appetite resulting in reduced energy intake, and we find it probable that this process is driven by exaggerated secretion of appetite-regulating gut hormones including, but probably not limited to, glucagon-like peptide-1 and peptide-YY. The increased secretion is due to an accelerated exposure to and absorption of nutrients in the small intestine. This places the weight loss and the gut hormones in key positions with respect to the metabolic improvements after bypass surgery.

Topics: Appetite; Bariatric Surgery; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Proteins; Digestion; Eating; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Intestinal Absorption; Nutrients; Obesity, Morbid; Peptide YY; Weight Loss

BACKGROUND Over the past few decades, bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become widely considered the most effective treatment for morbid obesity. In most cases, it results in enhanced glucose management in patients with obesity and type 2 diabetes (T2D), which is observed before significant weight loss. However, what accounts for this effect remains controversial. To gain insight into the benefits of RYGB in T2D, we investigated changes in the β-cell mass of obese rats following RYGB. MATERIAL AND METHODS RYGB or a sham operation was performed on obese rats that had been fed a high-fat diet (HFD) for 16 weeks. Then, the HFD was continued for 8 weeks in both groups. Additional normal chow diet (NCD) and obese groups were used as controls. RESULTS In the present study, RYGB induced improved glycemic control and enhanced β-cell function, which was reflected in a better glucose tolerance and a rapidly increased secretion of insulin and C-peptide after glucose administration. Consistently, rats in the RYGB group displayed increased β-cell mass and islet numbers, which were attributed in part to increased glucagon-like peptide 1 levels following RYGB. CONCLUSIONS Our data indicate that RYGB can improve b-cell function via increasing β-cell mass, which plays a key role in improved glycemic control after RYGB.

Topics: Animals; Bariatric Surgery; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Gastric Bypass; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islets of Langerhans; Male; Obesity; Obesity, Morbid; Rats; Rats, Sprague-Dawley; Weight Loss

An increase of bile acids (BAs), fibroblast growth factor 19 (FGF19), and glucagon-like peptide 1 (GLP-1) has been implicated in metabolic improvements after Roux-en-Y gastric bypass and vertical sleeve gastrectomy. However, data are still conflicting regarding their role after laparoscopic adjustable gastric banding (LAGB).. To assess the fasting BA, FGF19, and GLP-1 concentrations in plasma before and after LAGB and to test for correlations with immunometabolic parameters. Furthermore, hepatic farnesoid X receptor (FXR) expression and regulation of FXR-dependent genes were analyzed.. Observational study at the University Hospital Innsbruck.. Twenty obese patients.. Fasting plasma samples were taken before, 3, 6, and 12 months after LAGB. Liver biopsies were obtained at surgery and after 6 months postoperatively.. BA profiles, GLP-1 and FGF19 levels, hepatic FXR expression and regulation of FXR target genes were determined.. Total, conjugated, and secondary BAs transiently increased 3 months after LAGB (P < 0.01). Only one BA, glycolithocholic acid sulfate, remained significantly elevated throughout the whole follow-up period (P < 0.05). GLP-1 had increased transiently 3 months after surgery (P < 0.01), whereas FGF19 levels increased continuously (P < 0.05). Insulin, homeostasis model assessment index, C-reactive protein, FGF19, and GLP-1 correlated positively with different BAs. No differences were seen in hepatic FXR expression and FXR-regulated genes.. Our study results, not only identified LAGB-induced changes in BAs and BA-induced hormones, but also revealed associations between changes in BA profile with GLP-1 and FGF19.

Topics: Adult; Bariatric Surgery; Bile Acids and Salts; C-Reactive Protein; Female; Fibroblast Growth Factors; Gene Expression Regulation; Glucagon-Like Peptide 1; Glycocholic Acid; Humans; Immunohistochemistry; Insulin; Insulin Resistance; Laparoscopy; Liver; Male; Obesity, Morbid; Real-Time Polymerase Chain Reaction; Receptors, Cytoplasmic and Nuclear

Rapid gastric emptying has been proposed to justify the increase in glucagon-like polypeptide-1 (GLP-1) after laparoscopic sleeve gastrectomy (LSG).. To assess gastric emptying changes after LSG and their relationship with GLP-1 secretion.. San Salvatore Hospital general surgery unit, University of L'Aquila, Italy.. 52 patients underwent gastric emptying scintigraphy for liquid and solid foods, before and 3 months after LSG. Twenty-six patients were in the liquid group (L group) and the remaining in the solid group (S group). We evaluated the half time of gastric emptying (T. The rapid gastric emptying 3 months after LSG upregulates the production of GLP-1 in the distal bowel. Further studies are needed to confirm these findings.

Topics: Adult; Analysis of Variance; Bariatric Surgery; Female; Gastrectomy; Gastric Emptying; Glucagon-Like Peptide 1; Humans; Hypertension; Hypothyroidism; Laparoscopy; Male; Obesity, Morbid; Sleep Apnea Syndromes; Up-Regulation

Laparoscopic sleeve gastrectomy (LSG) has gained popularity as the leading bariatric procedure for the treatment of morbid obesity. Due to the rising numbers of bariatric surgeries, neurologic complications have become increasingly recognized. Our aim was to examine biochemical and hormonal factors that are associated with neuropathy post-LSG.. Thirty-two patients were included: 16 patients with neuropathy in the neuropathic group (NG) and 16 patients without neuropathy in the control group (CG). Diagnosis was made by a consultant neurologist, and blood samples were taken to examine vitamin deficiencies and hormones involved in neuropathy.. There was no significant difference between the BMI (p = 0.1) in both groups as well as excess weight loss percentages post-LSG at 12 months (p = 0.6). B12 levels were within normal range, but higher in NG (p = 0.005). Vitamin B1 and B2 levels were significantly lower in NG; p values are 0.000 and 0.031, respectively. Vitamin B6 levels were significantly higher in NG (p = 0.02) and copper levels were lower in NG (p = 0.009). There was no significant difference in GLP-1 response in both groups.. Our data showed post-LSG neuropathy is associated with lower levels of vitamin B1, B2, and copper, plus patients who are older in age. Vitamin B6 was significantly higher in the NG, which is, at toxic levels, associated with neuropathy. No difference in preoperative BMI, excess weight loss percent at 1 year, and GLP-1 levels was found. Larger data is required to validate our results.

Topics: Adult; Copper; Female; Gastrectomy; Glucagon-Like Peptide 1; Humans; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Treatment Outcome; Vitamin B Deficiency; Weight Loss

Topics: Bariatric Surgery; Caseins; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Satiation

Duodenal-jejunal bypass (DJB) has been proven effective in glycemic control in various type 2 diabetes (T2DM) rat models. "Hindgut hypothesis" and "foregut hypothesis" are two prevailing theories to elucidate the weight-independent anti-diabetic mechanisms of DJB, however, which mechanism plays the dominant role that has not been illuminated.. This paper aims to verify that exclusion of the foregut leads to loss of weight and remission of type 2 diabetes without expedited delivery of nutrients to the distal bowel.. Thirty-five diabetic rats induced by high-fat diet (HFD) and low dose of streptozotocin (STZ) were randomly assigned to the control, sham-DJB (S-DJB), DJB, ileal bypass (ILB), and DJB combined with ILB (DJB-ILB) groups. Effects of surgeries on body weight, food intake, blood glucose, glucose-stimulated insulin, and gastrointestinal hormones secretion were evaluated at indicated time points.. Compared to the control and S-DJB groups, the DJB group had significant and sustained glycemic control independent of weight loss. Excluding part of the distal ileum did not reverse the diabetic control that followed DJB surgery. The glucagon-like peptide 1 (GLP-1) and PYY levels were significantly increased after DJB. Although GLP-1 and PYY are mainly secreted by L cells in the distal ileum, excluding part of the ileum did not decrease the levels of GLP-1 and PYY after DJB.. The beneficial effects of DJB in glycemic control could not be reversed by excluding the distal ileum.

Topics: Anastomosis, Surgical; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Duodenum; Glucagon-Like Peptide 1; Ileum; Jejunum; Male; Obesity, Morbid; Peptide YY; Rats; Rats, Wistar

Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters.. Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed.. Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = -0.710, P = 0.001), and GLP-2 secretion (r = -0.561, P = 0.019).. IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.

Topics: Animals; Blood Glucose; Body Weight; Drinking; Eating; Enteroendocrine Cells; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Ileum; Insulin Resistance; Lipopolysaccharides; Male; Obesity, Morbid; Peptide YY; Rats, Sprague-Dawley

Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology.. Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified.. Shams consumed more food and gained more weight compared to both RYGB and BWM (p < 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p < 0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p < 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p < 0.05).. Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.

Topics: Animals; Blood Glucose; Caloric Restriction; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose Tolerance Test; Homeostasis; Hyperglycemia; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Male; Obesity, Morbid; Postprandial Period; Rats, Zucker; RNA, Messenger; Weight Loss

The Roux-en-Y gastric bypass (RYGB) is the gold standard bariatric operation. However, a major concern in late follow-up is the substantial weight regain. Understanding the role of gastrointestinal hormone secretion in this situation is relevant.. The aim of the present study was to evaluate the influence of gastrointestinal hormones comparing postprandial secretion of ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and leptin between patients with weight regain and those with favorable weight control. Twenty-four patients with follow-up from 27 to 59 months were divided into two groups according to sustained weight loss: group A (14 patients) had sustained weight losses, and group B (10 patients) had significant weight regain. Basal serum levels of ghrelin, GIP, GLP-1, and leptin after fasting and 30, 60, 90, and 120 min after a standard meal were measured.. There was no difference in the ghrelin secretion. There was a difference in the GIP secretion, with a higher percentage increase in 30 min in group A (330% × 192.2%; p = 0.01). There were also differences in the GLP-1 secretion, with higher increases in absolute (p = 0.03) and percentage values after 30 min in group A (124% × 46.5%; p = 0.01). There was also a difference between baseline leptin values, with higher levels in group B (p = 0.02).. The secretion of gut hormones in patients with weight regain after RYGB is different from that in patients with satisfactory weight outcome. After meal stimulation, reduced levels of GIP and GLP-1 may indicate the influence of gut hormones in the process of weight regain.

Topics: Adult; Bendamustine Hydrochloride; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Middle Aged; Obesity, Morbid; Postprandial Period; Weight Gain

Bile acids (BAs) have emerged as important signaling molecules in regulating metabolism and are closely related to gut microbiota. Bariatric surgery elevates serum BAs and affects gut microbiota universally. However, the specific profiles of postsurgical BA components and gut microbiota are still controversial. The aim of this study is to investigate the serum profiles of BA components and gut microbiota after duodenal-jejunal bypass (DJB).. DJB and SHAM procedures were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, insulin tolerance test, HOMA-IR, serum hormones, serum BAs, expression of BA transporters, and gut microbiota were analyzed at week 2 and week 12 postsurgery.. Compared with SHAM, DJB achieved rapid and durable improvement in glucose tolerance and insulin sensitivity, with enhanced GLP-1 secretion. DJB also elevated serum BAs, especially the taurine-conjugated BAs, with upregulation of BA transporters in the terminal ileum. The phylum level of Firmicutes and Proteobacteria abundance was increased postsurgery, at the expense of Bacteroidetes.. DJB preferentially increases serum taurine-conjugated BAs, probably because of more BA reabsorption in the terminal ileum. The gut microbiota is altered with more Firmicutes and Proteobacteria and less Bacteroidetes.

Topics: Animals; Bile Acids and Salts; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Duodenum; Gastric Bypass; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Jejunum; Male; Obesity, Morbid; Rats; Rats, Wistar; Taurine

Sleeve gastrectomy is an effective technique for the treatment of severe obesity, and its effects on the improved β-cell function have not yet been fully understood.. From February 2014 to July 2015, sleeve gastrectomy was performed in 5 patients with T2D, who were assessed before and after sleeve gastrectomy (SG). Moreover, a high-fat-diet (HFD) mouse model was also used to study the molecular mechanisms of β-cell functional improvement after SG.. The glucose-stimulated acute insulin response was restored in the T2D patients after SG. The expression of GLP-1 in colonic tissue as well as β-cell specific transcription factors (TFs), Pdx1, and MafA in islets was significantly increased after SG.. β-cell dysfunction can be ameliorated by SG. The re-activation of key TFs contributes to the improvement of β cell function.

Topics: Aged; Animals; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Gastrectomy; Glucagon-Like Peptide 1; Homeodomain Proteins; Humans; Insulin-Secreting Cells; Maf Transcription Factors, Large; Male; Mice; Mice, Inbred C57BL; Obesity, Morbid; Trans-Activators; Transcription Factors; Up-Regulation

Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP-1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up-regulated in AT of insulin-resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP-1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects.. We analysed the effects of GLP-1 on human AT and isolated adipocytes in vitro and the effects of GLP-1 mimetics on AT of morbidly obese T2D subjects in vivo.. GLP-1 down-regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP-1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3-L1 adipocytes, GLP-1 decreased free cytosolic Ca2+ concentration ([Ca2+]i). GLP-1-induced responses were only partially blocked by GLP-1 receptor antagonist exendin (9–39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects.. Our data suggest that the beneficial effects of GLP-1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP-1 receptor and an additional, as yet unknown, receptor.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Diabetes Mellitus, Type 2; Exenatide; Gene Expression; Genetic Markers; Glucagon-Like Peptide 1; Humans; Mice; Obesity, Morbid; Peptides; Pilot Projects; Prospective Studies; Venoms

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance (

Topics: Adiposity; Adult; Aged; Bariatric Surgery; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Duodenum; Female; Follow-Up Studies; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Jejunum; Male; Middle Aged; Obesity, Morbid; Treatment Outcome; Weight Loss

The correlation between resected gastric volume (RGV) and neuro-humoral changes (ghrelin and GLP-1) after laparoscopic sleeve gastrectomy (LSG) and their effects on type 2 diabetes mellitus (T2DM) has been evaluated.. Ninety-eight patients were divided in two groups: RGV <1200 mL (group A: 53 pts) and RGV >1200 mL (group B: 45 pts). Insulin secretion (insulin area under the curve (AUC)), insulinogenic index (IGI) and insulin-resistance (homeostasis model assessment, HOMA. A significant difference in T2DM resolution rate was observed after 6, 12 and 24 months in favour of RGV >1200 mL. Group B performed better than group A at the 3rd day and at the 6th, 12th and 24th months with regard to AUC, IGI and HOMA. Ghrelin and GLP-1 changes play a role in the regulation of glucose metabolism during the 1st year after LSG. RGV influences ghrelin and GLP-1 plasma levels after LSG, with a significant improvement in the T2DM control.

Topics: Adult; Bariatric Surgery; Diabetes Mellitus, Type 2; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Organ Size; Postoperative Period; Preoperative Period; Prospective Studies; Stomach

We determined whether persistent nausea and vomiting (N/V) symptoms following Roux-en-Y gastric bypass surgery is due to elevated systemic glucagon-like peptide-1 (GLP-1) and leptin in female non-diabetic subjects. Subjects with N/V post-Roux-en-Y gastric bypass (RYGB) surgery had significantly elevated fasting GLP-1 levels compared to that with post-operative asymptomatic subjects and to morbidly obese, obese and lean subjects not undergoing surgery. Weight loss, glycaemia, insulin and post-prandial GLP-1 levels were similar in all post-operative subjects. Despite comparable BMI, leptin was significantly lower in symptomatic subjects. Furthermore, leptin secretion from subcutaneous adipose tissue was inhibited by GLP-1 (0.1-1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1, but lower leptin levels. The latter may be a consequence of the direct GLP-1 inhibition of leptin secretion from adipose tissue.

Topics: Adipokines; Adult; Blood Glucose; Case-Control Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Nausea; Obesity, Morbid; Postoperative Nausea and Vomiting; Postprandial Period; Vomiting; Weight Loss

The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats.. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions.. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01).. CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

Topics: Acupuncture Points; Animals; Autonomic Nervous System; Blood Glucose; Body Weight; Eating; Electric Stimulation Therapy; Fasting; Gastrointestinal Motility; Ghrelin; Glucagon-Like Peptide 1; Male; Obesity; Obesity, Morbid; Peptide YY; Postprandial Period; Rats; Rats, Sprague-Dawley; Vagus Nerve

Clinical studies have shown similar rapid improvements in body mass and glycemic control after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG). Evidence suggests that adaptive intestinal tissue growth and reprogramming of intestinal glucose disposal play a key role in the beneficial effects on glucose homeostasis after RYGB, but it is not known whether such adaptive changes also occur after sleeve gastrectomy.. High-fat diet-induced obese rats were subjected to either VSG or RYGB, and intestinal growth and functional adaptations were assessed by using morphometric, immunohistochemical, and immuno-blot techniques, 3 months after surgery or sham surgery.. The cross-sectional areas of the Roux and common limbs are significantly increased after RYGB compared with sham surgery (Roux limb: 17.1 ± 4.0 vs. 5.5 ± 0.1 mm(2); common limb: 11.7 ± 0.6 vs. 5.1 ± 0.5 mm(2); p < 0.01), but the cross-sectional area of the corresponding jejunum is not different from controls after VSG. Similarly, mucosal thickness and the number of GLP-1 cells are not increased after VSG. Protein expression of hexokinase II is increased fourfold (p < 0.01) in the Roux limb after RYGB, but not in the jejunum after VSG.. Adaptive hypertrophy and reprogramming of glucose metabolism in the small intestine are not necessary for VSG to improve body composition and glycemic control. The similar beneficial effects of VSG and RYGB on glucose homeostasis might be mediated by different mechanisms.

Topics: Animals; Blood Glucose; Diet, High-Fat; Energy Metabolism; Gastrectomy; Glucagon-Like Peptide 1; Glucose; Hypertrophy; Intestinal Mucosa; Intestines; Jejunum; Male; Obesity, Morbid; Rats; Rats, Sprague-Dawley

Laparoscopic sleeve gastrectomy (SG) and gastric banding (GB) are popular bariatric procedures for treating morbid obesity. This study aimed to investigate changes in the hypothalamic feeding center after these surgeries in a diet-induced obese rat model.. Obesity was induced in 60 Sprague-Dawley rats using a high-energy diet for 6 weeks. These rats were divided into four groups: the sham-operated (SO) control, pair-fed (PF) control, SG and GB groups. Six weeks after the surgery, metabolic parameters, the plasma levels of leptin, ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) and the hypothalamic mRNA expressions of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) were measured.. Compared with those observed in the SO group, the body and fat tissue weights were significantly decreased and the metabolic parameters were significantly improved in the PF, SG and GB groups 6 weeks after surgery. The plasma ghrelin levels were significantly lower and the PYY and GLP-1 levels were significantly higher in the SG group than in the PF, GB and SO groups. Compared with that seen in the PF and GB groups, the hypothalamic mRNA expression of NPY was significantly lower and the expression of POMC was significantly higher in the SG group.. SG may affect the neurological pathway associated with appetite in the hypothalamus and thereby control ingestive behavior.

Topics: Animals; Bariatric Surgery; Disease Models, Animal; Feeding Behavior; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Hypothalamus; Leptin; Male; Neuropeptide Y; Obesity, Morbid; Peptide YY; Pro-Opiomelanocortin; Rats, Sprague-Dawley; RNA, Messenger

We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.. Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of GCG (encoding preproglucagon), PYY, CCK, GIP, GHRL (encoding ghrelin), SCT (encoding secretin), NTS (encoding neurotensin) and NR1H4 (encoding farnesoid X receptor) was evaluated.. The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups, GHRL, SCT and GIP mRNA was reduced after RYGB while PYY, CCK, NTS and NR1H4 gene expression was unaltered. GCG mRNA was upregulated in both groups.. Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG.

Topics: Adult; Cholecystokinin; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Proprotein Convertase 2; Treatment Outcome

The relation between hunger, satiation, and integrated gastrointestinal motility and hormonal responses in morbidly obese patients after sleeve gastrectomy has not been determined.. The objective was to assess the effects of sleeve gastrectomy on hunger, satiation, gastric and gallbladder motility, and gastrointestinal hormone response after a liquid meal test.. Three groups were studied: morbidly obese patients (n = 16), morbidly obese patients who had had sleeve gastrectomy (n = 8), and nonobese patients (n = 16). The participants fasted for 10 h and then consumed a 200-mL liquid meal (400 kcal + 1.5 g paracetamol). Fasting and postprandial hunger, satiation, hormone concentrations, and gastric and gallbladder emptying were measured several times over 4 h.. No differences were observed in hunger and satiation curves between morbidly obese and nonobese groups; however, sleeve gastrectomy patients were less hungry and more satiated than the other groups. Antrum area during fasting in morbidly obese patients was statistically significant larger than in the nonobese and sleeve gastrectomy groups. Gastric emptying was accelerated in the sleeve gastrectomy group compared with the other 2 groups (which had very similar results). Gallbladder emptying was similar in the 3 groups. Sleeve gastrectomy patients showed the lowest ghrelin concentrations and higher early postprandial cholecystokinin and glucagon-like peptide 1 peaks than did the other participants. This group also showed an improved insulin resistance pattern compared with morbidly obese patients.. Sleeve gastrectomy seems to be associated with profound changes in gastrointestinal physiology that contribute to reducing hunger and increasing sensations of satiation. These changes include accelerated gastric emptying, enhanced postprandial cholecystokinin and glucagon-like peptide 1 concentrations, and reduced ghrelin release, which together may help patients lose weight and improve their glucose metabolism after surgery. This trial was registered at clinicaltrials.gov as NCT02414893.

Topics: Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholecystokinin; Fasting; Female; Gastrectomy; Gastric Emptying; Gastrointestinal Hormones; Gastrointestinal Motility; Ghrelin; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Hunger; Insulin Resistance; Male; Meals; Middle Aged; Obesity, Morbid; Postprandial Period; Satiation

Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood.. Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB.. First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22). Second, we evaluated food intake (FI) following blockade of gut hormonal secretion in G-WL (n = 23) or P-WLM (n = 19) subjects. Finally, the impact of dietary-induced WL on the hormonal response in subjects with P-WLM (n = 14) was assessed.. This study was undertaken in a tertiary hospital.. In studies 1 and 3, the outcomes measures were the areas under the curve of gut hormones following a SMLM; in study 2, FI following subcutaneous injection of saline or octreotide were evaluated.. P-WLM associated a blunted GLP-1 (P = .044) and PYY (P = .001) responses and lesser suppression of ghrelin (P = .032) following the SMLM challenge. On saline day, FI in the G-WL (393 ± 143 kcal) group was less than in the P-WLM (519 ± 143 Kcal; P = .014) group. Octreotide injection resulted in enlarged FI in both groups (G-WL: 579 ± 248 kcal, P = .014; P-WLM: 798 ± 284 Kcal, P = .036), but the difference in FI between groups remained (P < .001). In subjects with P-WLM, dietary-induced WL resulted in larger ghrelin suppression (P = .046), but no change in the GLP-1 or PYY responses.. Our data show gastrointestinal hormones play a role in the control of FI following RYGB, but do not support that changes in GLP-1, PYY, or ghrelin play a major role as determinants of P-WLM after this type of surgery.

Topics: Adult; Case-Control Studies; Cohort Studies; Diet; Diet, Reducing; Eating; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Octreotide; Peptide YY; Treatment Outcome; Weight Loss

Both glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are gut hormones involved in energy homoeostasis. Obesity, insulin resistance and hyperglycaemia are significant confounders when GLP-1 and PYY secretion is assessed. Thus, we evaluated GLP-1 and PYY response after fat load in morbidly obese patients with different degrees of insulin resistance and glycemic status.. We studied 40 morbidly obese subjects (mean age, 40·6 ± 1·3 years; mean BMI, 53·1 ± 1·2 kg/m(2) ) divided into groups according to their glycemic status: normal fasting glucose (NFG) group, impaired fasting glucose (IFG) group and type 2 diabetes mellitus (T2D) group. NFG patients were additionally subclassified, according to the homoeostasis model assessment of insulin resistance (HOMAIR ), into a low insulin-resistance (LIR) group (HOMAIR <3·9) or a high insulin-resistance (HIR) group (HOMAIR ≥3·9).. Lipid emulsion was administered orally and measurements made at baseline and 180 min postprandially of levels of GLP-1, PYY, insulin, glucose, free fatty acids, triglycerides and leptin.. At the 180-minute postprandial reading, GLP-1 and PYY had increased in LIR-NFG subjects (41·84%, P = 0·01; 35·7%, P = 0·05; respectively), whereas no changes were observed in HIR-NFG, IFG or T2D subjects.. These results suggest that in morbidly obese subjects, both insulin resistance and abnormal glucose metabolism (IFG or T2D) impair the GLP-1 and PYY response to fat load. The implications of this attenuated enteroendocrine response should be elucidated by further studies.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon-Like Peptide 1; Homeostasis; Humans; Insulin Resistance; Lipids; Male; Middle Aged; Obesity, Morbid; Peptide YY

We assessed the acute impact of laparoscopic Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) compared to caloric-matched control group without surgery on glucose excursion in obese patients with type 2 diabetes, and examined if this was mediated by changes in insulin resistance, early insulin response or glucagon-like peptide (GLP)-1 levels.. Six-day subcutaneous continuous glucose monitoring (CGM) recordings were obtained from patients beginning 3 days before GBP (n = 11), SG (n = 10) or fasting in control group (n = 10). GLP-1, insulin and glucose were measured during 75 g oral glucose tolerance testing at the start and end of each CGM.. Post-operative hyperglycaemia occurred after both surgeries in the first 6 h, with a more rapid decline in glycaemia after GBP (p < 0.001). Beyond 24 h post-operatively, continuous overlapping of net glycaemia action reduced from baseline after GBP (median [interquartile range]) 1.6 [1.2-2.4] to 1.0 [0.7-1.3] and after SG 1.4 [0.9-1.8] to 0.7 [0.7-1.0]; p < 0.05), similar to controls (2.2 [1.7-2.5] to 1.3 [0.8-2.8] p < 0.05). Higher log GLP-1 increment post-oral glucose occurred after GBP (mean ± SE, 0.80 ± 0.12 vs. 0.37 ± 0.09, p < 0.05), but not after SG or control intervention. Among subgroup with baseline hyperglycaemia, a reduction in HOMA-IR followed GBP. Reduction in time and level of peak glucose and 2-h glucose occurred after both surgeries but not in controls.. GBP and SG have a similar acute impact on reducing glycaemia to caloric restriction; however, with a superior impact on glucose tolerance.

Topics: Adult; Bariatric Surgery; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Laparoscopy; Male; Middle Aged; Obesity, Morbid

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12 weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.

Topics: Adolescent; Adult; Appetite; Body Mass Index; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Laparoscopy; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces the gastric volume without implantable devices or gastrectomy. The aim of this study was to explore changes in glucose homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2 diabetes mellitus (T2DM) at 1 and 6 months after the procedure.. Thirteen morbidly obese T2DM women (mean age, 53.2 ± 8.76 years; body mass index, 40.1 ± 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6-month follow-up. At these time points, all study patients underwent a standardized liquid mixed-meal test, and blood was sampled for assessment of plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin, and obestatin.. All patients had significant weight loss both at 1 and 6 months after the LGCP (p ≤ 0.002), with mean percent excess weight loss (%EWL) reaching 29.7 ± 2.9% at the 6-month follow-up. Fasting hyperglycemia and hyperinsulinemia improved significantly at 6 months after the LGCP (p < 0.05), with parallel improvement in insulin sensitivity and HbA1c levels (p < 0.0001). Meal-induced glucose plasma levels were significantly lower at 6 months after the LGCP (p < 0.0001), and postprandial triglyceridemia was also ameliorated at the 6-month follow-up (p < 0.001). Postprandial GIP plasma levels were significantly increased both at 1 and 6 months after the LGCP (p < 0.0001), whereas the overall meal-induced GLP-1 response was not significantly changed after the procedure (p > 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the LGCP (p < 0.0001) with no significant changes in circulating obestatin levels.. During the initial 6-month postoperative period, LGCP induces significant weight loss and improves the metabolic profile of morbidly obese T2DM patients, while it also decreases circulating postprandial ghrelin levels and increases the meal-induced GIP response.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Laparoscopy; Middle Aged; Obesity, Morbid; Postprandial Period; Time Factors; Treatment Outcome; Triglycerides; Weight Loss

Low GLP-1 has been implicated in obesity and type 2 diabetes. Some studies reported reduced post-prandial GLP-1 levels in type 2 diabetics, whereas others reported GLP-1 levels not reduced in patients with impaired glucose tolerance (IGT) or type 2 diabetes. We undertook this study to evaluate the effect of obesity and pre-diabetes on GLP-1 levels in response to 75 g oral glucose.. Eighty subjects comprised four groups: 20 control subjects (normal weight and normal glucose tolerance (NGT)), 20 obese with NGT, 20 obese with impaired fasting glucose (IFG) and 20 obese with both IFG and impaired glucose tolerance (IGT). Laboratory tests included fasting blood glucose (FBG), 75 g glucose OGTT, fasting insulin and glucose-stimulated GLP-1 (30 min after 75 g glucose). Insulin resistance was quantified using HOMA-IR.. GLP-1 levels were significantly decreased in obese subjects compared to controls (571.17 ± 170.37 vs. 908.50 ± 169.90 pg/mL, p <0.001) and it was negatively correlated with body mass index (BMI) and waist circumference in all studied groups. Levels of GLP-1 were negatively correlated with HOMA-IR in all obese groups (r = -0.75, p <0.001). No significant difference was found in GLP-1 levels between all obese subjects (611.50 ± 187.96, 577.50 ± 150.85, 524.50 ± 167.35 pg/mL respectively, p >0.05). Morbidly obese cases (n = 15) had a significantly higher fasting insulin (25.20 ± 2.49 vs. 14 ± 3.81 μIU/ml), higher HOMA-IR (6.69 ± 1.2 vs. 3.48 ± 1.20), and lower GLP- 1 (212.0 ± 35.64 vs. 603.82 ± 136.35 pg/mL) (p <0.001) compared to non-morbid obese cases (n = 45).. Obesity reduces the GLP-1 levels. In insulin resistance, GLP-1 levels were reduced and it was related to the degree of insulin resistance.

Topics: Adult; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Obesity, Morbid; Prediabetic State

Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1.. We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS.. After BS, there was a significant reduction in body weight (p < 0.001), fasting plasma glucose (p < 0.001), fasting plasma insulin (p < 0.05), HOMA-IR (p < 0.001), and fasting plasma lipids (p < 0.05). The meal response of plasma triglycerides, total cholesterol, and HDL cholesterol was significantly lower compared to pre-intervention (p < 0.05, p < 0.001). In particular, the incremental area under the curve (IAUC) of plasma triglycerides decreased by 60% (p < 0.005). The meal-stimulated response of active GLP-1 increased, reaching a statistical significance (p < 0.001).. BS leads to an early improvement of fasting and postprandial lipemia. The fall in fasting triglycerides is associated with an improvement of insulin resistance, while the reduction of postprandial lipemia is likely related to reduced intestinal lipid absorption consequent to bariatric surgery.

Topics: Adult; Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Homeostasis; Humans; Hyperlipidemias; Incretins; Insulin Resistance; Lipids; Male; Middle Aged; Obesity, Morbid; Postprandial Period; Treatment Outcome; Triglycerides

Topics: Adult; Diabetes Mellitus, Type 2; Drug Synergism; Female; Glucagon-Like Peptide 1; Hirsutism; Humans; Hypoglycemic Agents; Liraglutide; Menstrual Cycle; Metformin; Obesity, Morbid; Polycystic Ovary Syndrome; Testosterone; Weight Loss

The mechanisms of weight loss after gastric bypass, including the role of gastric hormones, are still not completely understood. While postprandial releases of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) increase post-surgery and ghrelin usually is reduced, their relationship to the magnitude of the weight loss is still obscure. We explored if differing weight loss after Roux Y gastric bypass (RYGB) in morbidly obese were associated with differing postprandial hormonal release.. We compared patients with large (> 40%) or moderate (< 25%) weight loss three years following RYGP surgery, and an obese control group scheduled for RYGB (six in each group). A 300 kcal mixed meal test was given with blood sampling before and thereafter at 30-min intervals in 180 min. Peak and incremental area under the curve (iAUC) were calculated to characterize postprandial responses.. Early postprandial GLP-1 response were significantly higher in the RYGB groups than in the controls, and highest in those with largest weight loss. Postprandial PYY response were also greater for the two RYGB groups vs. controls, but interestingly the controls had higher baseline values. Ghrelin, from similar baseline, was only suppressed in those with the largest weight loss, with close to no reduction in those with modest weight loss or controls.. These results support the hypothesis that the magnitude of weight loss after RYGB surgery might be associated with differing patterns of postprandial responses in GLP-1 and ghrelin, but not PYY. Larger studies are warranted.

Topics: Adult; Anastomosis, Roux-en-Y; Area Under Curve; Female; Gastric Bypass; Gastric Mucosa; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Stomach; Weight Loss

The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on β-cell function and β-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in β-cell mass, islet number, and number of extraislet β-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved β-cell function and β-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.

Topics: Animals; Blood Glucose; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Insulin; Insulin-Secreting Cells; Male; Obesity, Morbid; Swine

Topics: Appetite; Bariatric Surgery; Bile Acids and Salts; Gastric Bypass; Gastric Emptying; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Microbiota; Obesity, Morbid; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Treatment Outcome

To assess the rapid improvement of insulin sensitivity and β-cell function following biliopancreatic diversion with duodenal switch (BPD-DS) and determine the role played by caloric restriction in these changes.. Standard meals were administrated before and on day 3, 4, and 5 after BPD-DS to measure total caloric intake, glucose excursion, insulin sensitivity, and secretion in matched type 2 diabetes and normoglycemic (NG) subjects. In a second set of study, other subjects with type 2 diabetes had the same meal tests prior to and after a 3-day caloric restriction identical to that observed after BPD-DS and then 3 days after actually undergoing BPD-DS.. Improvement of HOMA-IR occurred at day 3 after BPD-DS in diabetes and after 3 days of caloric restriction. The disposition index (DI) improved rapidly in diabetes after BPD-DS and to a similar extent after caloric restriction. DI was higher and did not change after BPD-DS in NG. Changes in glucagon-like peptide-1, gastric inhibitory peptide, peptide tyrosine tyrosine, ghrelin, and pancreatic polypeptide levels were not associated with modulation of DI in the participants.. Caloric restriction is the major mechanism underlying the early improvement of insulin sensitivity and β-cell function after BPD-DS in type 2 diabetes.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Duodenum; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Obesity, Morbid; Peptide YY; Pilot Projects

Bariatric surgery is the most effective therapeutic option for obesity and its complications, especially in type 2 diabetes. The aim of this study was to investigate the messenger RNA (mRNA) gene expression of proglucagon, glucose-dependent insulinotropic peptide (GIP), prohormone convertase 1/3 (PC1/3), and dipeptidyl peptidase-IV (DPP-IV) in jejunum cells of the morbidly obese (OB) non type 2 diabetes mellitus (NDM2) and type 2 diabetes mellitus (T2DM), to determine the molecular basis of incretin secretion after bariatric surgery.. Samples of jejunal mucosa were obtained from 20 NDM2 patients: removal of a section of the jejunum about 60 cm distal to the ligament of Treitz and 18 T2DM patients: removal of a section of the jejunum about 100 cm distal to the ligament of Treitz. Total RNA was extracted using TRIzol. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out. Samples were sequenced to PC1/3 by ACTGene Análises Moleculares Ltd. Immuno content was quantified with a fluorescence microscope.. T2DM showed decreased PC1/3 mRNA expression in the primers tested (primer a, p=0.014; primer b, p=0.048). Many patients (36.5 %) did not express PC1/3 mRNA. NDM2 and T2DM subjects showed nonsignificantly different proglucagon, GIP, and DPP-IV mRNA expression. The immuno contents of glucagon-like peptide-1 and GIP decreased in T2DM jejunum, but incubation with high glucose stimulated the immuno contents.. The results suggest that bioactivation of pro-GIP and proglucagon could be impaired by the lower expression of PC1/3 mRNA in jejunum cells of obese patients with T2DM. However, after surgery, food could activate this system and improve glucose levels in these patients.

Topics: Adult; Case-Control Studies; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Female; Gastric Inhibitory Polypeptide; Gene Expression Regulation; Glucagon-Like Peptide 1; Humans; Jejunum; Male; Middle Aged; Obesity, Morbid; Proprotein Convertase 1; Real-Time Polymerase Chain Reaction; RNA, Messenger

Although GLP-1 has been suggested as a major factor for the marked improvement of glucose tolerance commonly seen after sleeve gastrectomy (SG), several observations challenge this hypothesis. To better understand the role of GLP-1 in the remission of type 2 diabetes mellitus (T2DM) long term after SG in humans, we conducted two separate cross-sectional studies: 1) the GLP-1 response to a standardized mixed liquid meal (SMLM) was compared in subjects with T2DM antedating SG but with different long-term (>2 years) T2DM outcomes (remission, relapse, or lack of remission) (study 1) and 2) the effect of GLP-1 receptor blockade with exendin (9-39) on glucose tolerance was examined in subjects with T2DM antedating surgery, who had undergone SG and presented with long-term T2DM remission (study 2). In study 1, we observed a comparable GLP-1 response to the SMLM regardless of the post-SG outcome of T2DM. In study 2, the blockade of GLP-1 action resulted in impaired insulin secretion but limited deterioration of glucose tolerance. Thus, our data suggest the enhanced GLP-1 secretion observed long term after SG is neither sufficient nor critical to maintain normal glucose tolerance in subjects with T2DM antedating the surgery.

Topics: Adult; Aged; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Gastrectomy; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Male; Middle Aged; Obesity, Morbid

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastroplasty; Glucagon-Like Peptide 1; Humans; Laparoscopy; Obesity, Morbid; Triglycerides; Weight Loss

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastroplasty; Glucagon-Like Peptide 1; Humans; Laparoscopy; Obesity, Morbid; Triglycerides; Weight Loss

Changes in gastrointestinal peptide release may play an important role in improving glucose control and reducing body weight following Roux-en-Y gastric bypass (RYGB), but the impact of low caloric intake on gut peptide release post-surgery has not been well characterized. The purpose of this study was to assess the relationships between low caloric intake and gut peptide release and how they were altered by RYGB. Obese females including ten normoglycemic (ON) and ten with type 2 diabetes mellitus (T2DM) (OD) were studied before, 1 week, and 3 months after RYGB. Nine lean, normoglycemic women were studied for comparison. Subjects were given three separate mixed meal challenges (MMCs; 75, 150, and 300 kcal). Plasma glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were analyzed. Prior to surgery, only minimal increases in GLP-1 and PYY were observed in response to the MMCs. After surgery, the peak GLP-1 concentration was progressively elevated in response to increasing meal sizes. The meal sizes had a statistically significant impact on elevation of GLP-1 incremental areas under the curve (ΔAUC) in both ON and OD at 1 week and 3 months post-surgery visits (p < 0.05 for all comparisons). The PYY ∆AUC was also significantly increased in a meal size-dependent manner in both ON and OD at both post-surgery visits (p < 0.05 for all comparisons). Meal sizes as small as 75-300 kcal, which cause minimal stimulation in GLP-1 or PYY release in the subjects before RYGB, are sufficient to provide statistically significant, meal size-dependent increases in the peptides post-RYGB both acutely and after meaningful weight loss occurred.

Topics: Adult; Anastomosis, Roux-en-Y; Diabetes Mellitus, Type 2; Female; Food; Glucagon-Like Peptide 1; Humans; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Male; Obesity, Morbid

To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).. Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender.. Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite.. Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition.. Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Topics: Absorptiometry, Photon; Appetite Regulation; Bile Acids and Salts; Blood Glucose; Body Mass Index; Cholecystokinin; Cross-Sectional Studies; Dumping Syndrome; Energy Metabolism; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Neurotensin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

Topics: Aged; Body Mass Index; Dyslipidemias; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin; Middle Aged; Obesity, Morbid; Sleep Apnea, Obstructive; Treatment Outcome; Weight Loss

Transoral gastroplasty (TOGA) is a safe and less invasive procedure than traditional bariatric surgery. We studied the effects of TOGA on the risk of progression from prediabetes to overt type 2 diabetes mellitus (T2DM) or on regression from diabetes or prediabetes to a lower risk category.. Prospective, observational study (October 2008 to October 2010) performed at Catholic University, Rome, Italy. Fifty consecutive subjects 18-60 years old, 35 ≥ body mass index < 55 kg/m², were enrolled. Glucose tolerance, insulin sensitivity, and secretion were studied at baseline and 1 week and 1, 6, and 12 months after TOGA. Plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and ghrelin levels were measured.. Forty-three patients (86%) completed the 1-year postoperative follow-up. Patients lost 16.90% of baseline weight (P level × factor time <0.001). Body mass index decreased from 42.24 ± 3.43 to 34.65 ± 4.58 kg/m² (P < .001). Twenty-three patients (53.5%) were diagnosed as normal glucose tolerance (NGT) before treatment, 2 (4.6%) were impaired fasting glucose (IFG), 12 (27.9%) were impaired glucose tolerance (IGT), 1 (2.3%) had both IFG and IGT, and 5 (11.6%) had T2DM. At 1-year posttreatment, the percentages changed to 86.0% NGT, 2.3% IFG, 11.6% IGT, 0% IFG plus IGT, and 0% T2DM, respectively. Peripheral insulin resistance and homeostasis model of assessment-insulin resistance improved significantly. Fasting glucose-dependent insulinotropic peptide and ghrelin decreased from 316.9 ± 143.1 to 156.2 ± 68.2 pg/mL (P < .001) and from 630.6 ± 52.1 to 456.7 ± 73.1 pg/mL (P < .001), respectively, whereas GLP-1 increased from 16.2 ± 4.9 to 23.7 ± 9.5 pg/mL (P < .001).. TOGA induced glucose disposal improvement with regression of diabetes to NGT or IGT and regression of IGT and IFG to NGT in half of the cases. Regressors showed a much larger increase of GLP-1 levels than progressors.

Topics: Adolescent; Adult; Body Mass Index; Coronary Disease; Diabetes Mellitus, Type 2; Disease Progression; Follow-Up Studies; Gastric Inhibitory Polypeptide; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Middle Aged; Obesity; Obesity, Morbid; Prediabetic State; Prospective Studies; Risk; Rome; Weight Loss; Young Adult

Weight regain after gastric bypass (GBP) can be associated with a gastrogastric fistula (GGF), in which a channel forms between the gastric pouch and gastric remnant, allowing nutrients to pass through the "old route" rather than bypassing the duodenum. To further understand the mechanisms by which GGF may lead to weight regain, we investigated gut hormone levels in GBP patients with a GGF, before and after repair.. Seven post-GBP subjects diagnosed with GGF were studied before and 4 months after GGF repair. Another cohort of 22 GBP control subjects without GGF complication were studied before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3-36, GIP, and GLP-1 levels.. Four months after GGF repair subjects lost 6.0 ± 3.9 kg and had significantly increased postprandial PYY3-36 levels. After GGF repair, fasting and postprandial ghrelin levels decreased and were strongly correlated with weight loss. The insulin response to glucose also tended to be increased after GGF repair, however no concomitant increase in GLP-1 was observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels were no longer lower than the post-GBP group.. These data utilize the GGF model to highlight the possible role of duodenal shunting as a mechanism of sustained weight loss after GBP, and lend support to the potential link between blunted satiety peptide release and weight regain.

Topics: Adult; Blood Glucose; Body Mass Index; Endoscopy, Gastrointestinal; Female; Gastric Bypass; Gastric Fistula; Gastrointestinal Hormones; Gastroscopy; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Laparoscopy; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Postoperative Complications; Postoperative Period; Preoperative Period; Suture Techniques; Time Factors; Treatment Outcome; United States; Weight Loss

To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP).. Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition.. Patients in G1 presented a lower area under the curve (AUC0-120) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC0-120 of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger β-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups.. Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that β-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.

Topics: Absorptiometry, Photon; Aged; Biomarkers; Blood Glucose; Body Composition; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Treatment Outcome

Fibroblast growth factor (FGF)-19 and FGF-21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF-19 and FGF-21 along with circulating bile acids and other relevant hormonal and biochemical parameters.. Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG.. LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state.. Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.

Topics: Adiponectin; Adult; Bile Acids and Salts; Body Mass Index; C-Reactive Protein; Female; Fibroblast Growth Factors; Gastrectomy; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Leptin; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Prospective Studies; Resistin; RNA, Messenger; Subcutaneous Fat; Waist Circumference; Weight Loss

To investigate the impacts of laparoscopic bariatric surgery on fasting glucagon-like peptide-1 (GLP-1) and Ghrelin level in patients with type 2 diabetes mellitus (T2DM), and the mechanism in surgical treatment of T2DM.. From March 2010 to August 2011, 44 patients with T2DM underwent laparoscopic bariatric, including laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 14), laparoscopic mini-gastric bypass (LMGB, n = 11), laparoscopic sleeve gastrectomy (LSG, n = 9) and laparoscopic adjustable gastric banding (LAGB, n = 10). The curative effects, changes of metabolism and gastrointestinal hormones were analyzed respectively.. Within 6 months after surgery, the clinical complete remission of T2DM was 11, 8, 6, 3 cases in LRYGB, LMGB, LSG, LAGB group respectively; the clinical partial remission was 3, 3, 2, 4 cases respectively. The inefficacy was 1, 3 patients in LSG and LAGB group respectively. The effects of surgery within 6 months postoperative among 4 groups were different (χ(2) = 8.162, P < 0.05). The levels of body mass index (F = 275.29) and homeostasis model assessment of insulin resistance (F = 40.09) of 4 groups were declined in 6 months postoperatively (P < 0.01). The extents of decrease were no significance among 4 groups. Compared to preoperative level, GLP-1 in LRYGB ((116 ± 33) vs. (66 ± 20) ng/L and LMGB group ((103 ± 22) vs. (65 ± 16) ng/L) was higher in the first month after surgery (F = 21.76 and 139.21, P < 0.05). The changes in LSG and LAGB group were no significance (P > 0.05). The level of Ghrelin in LRYGB, LMGB, LSG group at the first week after surgery were (208 ± 79), (275 ± 102) and (258 ± 91) ng/L respectively, and they were lower than preoperative (there were (398 ± 114), (439 ± 96) and (446 ± 105) ng/L, F = 55.08, 49.96 and 46.47, all P < 0.01). But the level of Ghrelin in LRYGB and LMGB groups rebounded in the first postoperative month. The postoperative level of Ghrelin was higher in LAGB group (F = 29.24, P = 0.001).. There are difference efficacies and impacts on gastrointestinal hormones among different modes of bariatric surgery. The change of gastrointestinal hormones is plausible mechanism of T2DM remission after surgery.

Topics: Adult; Diabetes Mellitus, Type 2; Endoscopy, Gastrointestinal; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Humans; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Young Adult

In obese patients with type 2 diabetes (T2DM), Roux-en-Y-gastric-bypass (RYGB) and sleeve gastrectomy (SLG) improve glycemic control.. The objective of this study was to investigate the mechanisms of surgery-induced T2DM improvement and role of gastrointestinal hormones. PATIENTS, SETTING, AND INTERVENTION: In 35 patients with T2DM, we performed a mixed-meal test before and 15 days and 1 year after surgery (23 RYGB and 12 SLG).. Insulin sensitivity, β-cell function, and amylin, ghrelin, PYY, pancreatic polypeptide (PP), glucagon, and glucagon-like peptide-1 (GLP-1) responses to the meal were measured.. T2DM remission occurred in 13 patients undergoing RYGB and in 7 patients undergoing SLG. Similarly in the RYGB and SLG groups, β-cell glucose sensitivity improved both early and long term (P < .005), whereas insulin sensitivity improved long term only (P < .006), in proportion to body mass index changes (P < .001). Early after RYGB, glucagon and GLP-1 responses to the meal increased, whereas the PP response decreased. At 1 year, PYY was increased, and PP, amylin, ghrelin, and GLP-1 were reduced. After SLG, hormonal responses were similar to those with RYGB except that PP was increased, whereas amylin was unchanged. In remitters, fasting GLP-1 was higher (P = .04), but its meal response was flat compared with that of nonremitters; postsurgery, however, the GLP-1 response was higher. Other hormone responses were similar between the 2 groups. In logistic regression, presurgery β-cell glucose sensitivity (positive, P < .0001) and meal-stimulated GLP-1 response (negative, P = .004) were the only predictors of remission.. RYGB and SLG have a similar impact on diabetes remission, of which baseline β-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glycemic Index; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Remission Induction

The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia.. We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms.. Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements.. These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Incretins; Male; Middle Aged; Obesity, Morbid; Postprandial Period; Treatment Outcome

We describe the effectiveness of liraglutide therapy in a severely insulin-resistant patient with type 2 diabetes mellitus (DM-2) requiring U-500 insulin.. A 65-year-old morbidly obese man (body mass index, 67.3 kg/m(2); weight, 156.2 kg) presented with a 20-year history of DM-2; the glycemic control deteriorated to U-500 insulin requirement. He was inadequately controlled (hemoglobin A1c [HbA1c], 9.1%) on metformin plus U-500 insulin titrated to 575 units daily. Liraglutide was added and titrated to 1.8 mg once daily over 3 weeks.. Insulin requirements decreased markedly (>50%) to 250 units daily after 5 months of added liraglutide, with a concurrent improvement in HbA1c from 9.1% to 6.9% and weight loss of 22.6 kg.. The addition of once-daily liraglutide to the regimen of patients with uncontrolled DM-2 requiring U-500 insulin should be considered as it may help to reduce insulin requirements, improve glycemic control, and assist with weight management.

Topics: Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Liraglutide; Male; Obesity, Morbid; Severity of Illness Index; Treatment Outcome

To elucidate the mechanisms of improvement/reversal of type 2 diabetes after Roux-en-Y gastric bypass (RYGB).. Fourteen morbidly obese subjects, 7 with normal glucose tolerance and 7 with type 2 diabetes, were studied before and 1 month after RYGB by euglycemic hyperinsulinemic clamp (EHC), by intravenous glucose tolerance test (IVGTT) and by oral glucose tolerance test (OGTT) in 3 different sessions. Intravenous glucose tolerance test IVGTT and OGTT insulin secretion rate (ISR) and sensitivity were obtained by the minimal model. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. Six healthy volunteers were used as controls.. Total ISR largely increased in diabetic subjects only when glucose was administered orally (37.8 ± 14.9 vs 68.3 ± 22.8 nmol; P < 0.05, preoperatively vs postoperatively). The first-phase insulin secretion was restored in type 2 diabetic after the IVGTT (Φ1 × 10: 104 ± 54 vs 228 ± 88; P < 0.05, preoperatively vs postoperatively; 242 ± 99 in controls). Insulin sensitivity by EHC (M × 10) was slightly but significantly improved in both normotolerant and diabetic subjects (1.46 ± 0.22 vs 1.37 ± 0.55 mmol·min·kg; P < 0.05 and 1.53 ± 0.23 vs 1.28 ± 0.62 mmol·min·kg; P < 0.05, respectively). Quantitative insulin sensitivity check index was improved in all normotolerant (0.32 ± 0.02 vs 0.30 ± 0.02; P < 0.05) and diabetic subjects (0.33 ± 0.03 vs 0.31 ± 0.02; P < 0.05). GIP and GLP-1 levels increased both at fast and after OGTT mainly in type 2 diabetic subjects.. The large increase of ISR response to the OGTT together with the restoration of the first-phase insulin secretion in diabetic subjects might explain the reversal of type 2 diabetes after RYGB. The large incretin secretion after the oral glucose load might contribute to the increased ISR.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity, Morbid; Treatment Outcome

The effects of gastric bypass surgery on the secretion of the anorexigenic gut-derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), independent of caloric restriction and due to different dietary macronutrients, is not well characterized. This study examines the effects of a mixed-nutrient or high-fat liquid meal on the postprandial stimulation of GLP-1 and PYY following gastric bypass or equivalent hypocaloric diet.. Total PYY and active GLP-1 were measured fasting and at multiple points after standardized mixed-nutrient and high-fat liquid meals in two matched groups of obese subjects. The meal stimulation tests were performed before and 14.6 ± 3.3 days after gastric bypass (GBP, n = 10) and before and after a 7-day hypocaloric liquid diet matching the post-GBP diet (control, n = 10).. Mixed-nutrient and high-fat postprandial GLP-1 levels increased following GBP (mixed-nutrient peak: 85.0 ± 28.6-323 ± 51 pg/ml, P < 0.01; high-fat peak: 81.8 ± 9.6-278 ± 49 pg/ml, P < 0.01), but not after diet (mixed-nutrient peak: 104.4 ± 9.4-114.9 ± 15.8 pg/ml, P = NS; high-fat peak: 118.1 ± 16.4-104.4 ± 10.8 pg/ml, P = NS). The postprandial PYY response also increased after GBP but not diet, though the increase in peak PYY did not reach statistical significance (GBP mixed-nutrient peak: 134.8 ± 26.0-220.7 ± 52.9 pg/ml, P = 0.09; GBP high-fat peak: 142.1 ± 34.6-197.9 ± 12.7 pg/ml, P = 0.07; diet mixed-nutrient peak: 99.8 ± 8.0-101.1 ± 13.3 pg/ml, P = NS; diet high-fat peak: 105.0 ± 8.8-103.1 ± 11.8 pg/ml, P = NS). The postprandial GLP-1 response was not affected by the macronutrient content of the meal. However, following GBP the mixed-nutrient PYY total area under the curve (AUC(0-120)) was significantly greater than the high-fat PYY AUC(0-120) (22,081 ± 5,662 pg/ml min vs. 18,711 ± 1,811 pg/ml min, P = 0.04).. Following GBP there is an increase in the postprandial stimulation of PYY and GLP-1 that is independent of caloric restriction. The phenomenon of "bariatric surgery-induced anorexia" may be linked to the increased levels after GBP.

Topics: Adolescent; Adult; Aged; Appetite; Body Mass Index; Caloric Restriction; Case-Control Studies; Diabetes Mellitus, Type 2; Diet, High-Fat; Fasting; Female; Food; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss; Young Adult

Postprandial hypoglycaemia is a severe complication of Roux-en-Y gastric bypass (RYGBP). Acarbose, an α-glucosidase inhibitor (AGI), is employed in its treatment. Several studies have shown that AGIs increase the postprandial levels of glucagon-like peptide 1 (GLP-1). However, an excessive level of GLP-1 is one of the factors involved in the physiopathology of this condition. We analysed the effect of acarbose oral administration in eight RYBGP patients with clinically significant hypoglycaemia or dumping syndrome.. Glucose, insulin and GLP-1 plasma levels in fasting and after ingestion of a standard meal (Ensure Plus®; 13 g protein, 50 g carbohydrate, 11 g fat) were measured. The test was repeated the following week with the oral administration of 100 mg of acarbose 15 min prior to the meal.. Five patients developed asymptomatic hypoglycaemia during the test (glucose level <50 mg/dl) with inappropriately high insulin levels and exaggerated GLP-1 response. Acarbose ingestion avoided hypoglycaemia in all of the patients and increased the lowest plasma glucose level (46.4 ± 4.8 vs. 59.0 ± 2.6 mg/dl, p < 0.01). Acarbose ingestion decreased the area under the curve for serum insulin and GLP-1 levels at 15 min after the meal.. Acarbose avoided postprandial hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This was associated with a decrease in early GLP-1 secretion, in contrast to that observed in non-surgical subjects. This finding could be explained by the reduction of glucose load in the jejunum produced by the α-glucosidase inhibition, which is the main stimulus for GLP-1 secretion.

Topics: Acarbose; Administration, Oral; Adult; Blood Glucose; Diabetes Mellitus; Dumping Syndrome; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Insulin; Male; Obesity, Morbid; Postprandial Period; Treatment Outcome

The aim of this study was to evaluate the pathophysiological mechanisms underlying the non-remission of type 2 diabetes in Roux-en-Y gastric bypass (RYGB) patients.. A group of patients not in remission (NR) was formed (n = 13). A remission group (R) was composed of patients who had undergone normalization of fasting glycemia and A1c, without anti-diabetic drugs and matched for selected baseline characteristics (i.e., duration of disease, previous BMI, final BMI, fat distribution, and age; n = 15). A control group of lean subjects (n = 41) was formed.. The NR group had higher uric acid (5.1 vs. 3.9 mg/dL), number of leukocytes (6,866.9 vs. 5,423.6), hs-CRP (0.27 vs. 0.12 mg/dL), MCP-1 (118.4 vs. 64.4 ng/mL), HOMA-IR, and AUC(glucose) but lower adiponectin (9.4 vs. 15.4 ng/mL), leptin (12.7 vs. 20.7 ng/mL), and AUC(GLP-1) in comparison to R group; the NR group also had lower leptin and higher adiponectin, HOMA-IR, AUC(glucose), AUC(C-peptide), AUC(glucagon), and AUC(GLP-1) than controls. The R group had lower MCP-1 and higher adiponectin compared to controls. Insulin sensitivity was significantly lower in the NR group than in the R and control groups. The insulin secretion index values were lower in the NR group than in the R and control groups.. This study found greater insulin resistance, lower insulin secretion, persistent adiposopathy and chronic subclinical inflammation, and less robust incretin response in the NR group despite a similar level of weight loss. Persistently altered pathophysiological mechanisms can be related to the lack of remission of type 2 diabetes after RYGB.

Topics: Adiponectin; Adolescent; Adult; Area Under Curve; Blood Glucose; Body Mass Index; Brazil; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Incretins; Leukocytes; Male; Middle Aged; Obesity, Morbid; Remission Induction; Retrospective Studies; Uric Acid; Weight Loss; Young Adult

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

Oral meal consumption increases glucagon-like peptide 1 (GLP-1) release which maintains euglycemia by increasing insulin secretion. This effect is exaggerated during short-term follow-up of Roux-en-y gastric bypass (RYGB). We examined the durability of this effect in patient with type 2 diabetes (T2DM) >10 years after RYGB.. GLP-1 response to a mixed meal in the 10-year post-RYGB group (n = 5) was compared to lean (n = 9), obese (n = 6), and type 2 diabetic (n = 10) controls using a cross-sectional study design. Analysis of variance (ANOVA) was used to evaluate GLP-1 response to mixed meal consumption from 0 to 300 min, 0-20 min, 20-60 min, and 60-300 min, respectively. Weight, insulin resistance, and T2DM were also assessed.. GLP-1 response 0-300 min in the 10-year post-RYGB showed a statistically significant overall difference (p =  0.01) compared to controls. Furthermore, GLP-1 response 0-20 min in the 10-year post-RYGB group showed a very rapid statistically significant rise (p = 0.035) to a peak of 40 pM. GLP-1 response between 20 and 60 min showed a rapid statistically significant (p = 0.041) decline in GLP-1 response from ~40 pM to 10 pM. GLP-1 response in the 10-year post-RYGB group from 60 to 300 min showed no statistically significant difference from controls. BMI, HOMA, and fasting serum glucose before and >10 years after RYGB changed from 59.9 → 40.4, 8.7 → 0.88, and 155.2 → 87.6 mg/dl, respectively, and were statistically significant (p < 0.05).. An exaggerated GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. This phenomenon may play a key role in maintaining type 2 diabetes remission and weight loss after RYGB.

Topics: Analysis of Variance; Blood Glucose; Body Weight; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Eating; Female; Follow-Up Studies; Gastric Bypass; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Time Factors; Treatment Outcome; Weight Loss

Bariatric surgical procedures, including the laparoscopic adjustable gastric band (LAGB), are currently the only effective treatments for morbid obesity, however, there is no clear understanding of the mechanisms underpinning the efficacy of LAGB. The aim of this study is to examine changes in activation of the sensory neuronal pathways and levels of circulating gut hormones associated with inflation of an AGB.. The trajectory within the central nervous system of polysynaptic projections of sensory neurons innervating the stomach was determined using the transsynaptically transported herpes simplex virus (HSV). Populations of HSV-infected neurons were present in the brainstem, hypothalamus and cortical regions associated with energy balance. An elevation of Fos protein was present within the nucleus of the solitary tract, a region of the brainstem involved in the control of food intake, following acute and chronic band inflation. Two approaches were used to test (1) the impact of inflation of the band alone (on a standard caloric background) or (2) the impact of a standard caloric meal (on the background of the inflated band) on circulating gut hormones. Importantly, there was a significant elevation of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) following oral gavage of a liquid meal in animals with pre-inflated bands. There was no impact of inflation of the band alone on circulating GLP-1, PYY or ghrelin in animals on a standard caloric background.. These data are consistent with the notion that the LAGB exerts its effects on satiety, reduced food intake and reduced body weight by the modulation of both neural and hormonal responses with the latter involving an elevation of meal-related levels of GLP-1 and PYY. These data are contrary to the view that the surgery is purely 'restrictive'.

Topics: Animals; Brain; Caloric Restriction; Disease Models, Animal; Eating; Gastric Mucosa; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Laparoscopy; Male; Obesity, Morbid; Peptide YY; Rats; Rats, Sprague-Dawley; Satiation; Sensory Receptor Cells; Signal Transduction; Simplexvirus; Stomach; Weight Loss

The objective of this study was to evaluate sleeve gastrectomy with jejunal bypass (SGJB) as a surgical treatment for type 2 diabetes mellitus (T2DM) in patients with a body mass index (BMI) <35 kg/m(2). This is a prospective cohort study. Patients with T2DM and BMI <35 kg/m(2) who underwent SGJB between January 2009 and June 2011 at DIPRECA Hospital, in Santiago, and Hospital Base, Osorno, Chile were included. SGJB consists of creating a gastric tube, which preserves the pylorus, and performing a jejunoileal anastomosis 300 cm distal to the angle of Treitz. Excess weight loss (EWL) and complete or partial remission of T2DM were reported. Forty-nine patients met the inclusion criteria. The mean age was 49 years (36-62), and 53 % of patients were female. Mean preoperative BMI was 31.6 kg/m(2) (25-34.9 kg/m(2)). Operation time was 123 ± 14 min, with 94.7 % of operations performed laparoscopically. Mean postoperative hospital stay was 2 days. Mean postoperative follow-up was 12 months. Median EWL at 1, 3, 6, 12, and 18 months postoperatively was 31.9 %, 56.9 %, 76.1 %, 81.5 %, and 76.1 %, respectively. Complete T2DM remission was achieved in 81.6 % of patients (40/49) and partial remission in 18.4 % (9/49). Forty of 41 patients (97.6 %) on oral hypoglycemic agents achieved complete T2DM remission, and 100 % of insulin-dependent patients stopped using insulin but were still being treated for T2DM. One patient experienced postoperative gastrointestinal bleeding. There were no deaths. SGJB is an effective treatment for T2DM in patients with BMI <35 kg/m(2).

Topics: Adult; Blood Glucose; Body Mass Index; Chile; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastroplasty; Glucagon-Like Peptide 1; Humans; Jejunum; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss

Previous studies addressing the changes of glucagon-like peptide-1 (GLP-1) concentrations in morbidly obese patients after bariatric surgery have demonstrated conflicting results. The aim of the present study was to investigate the changes in serum GLP-1 levels 9 months after biliopancreatic diversion in morbidly obese patients without diabetes mellitus.. A sample of 40 morbidly obese patients without diabetes mellitus was enrolled. Biochemical and anthropometrical evaluations were conducted at basal and 9 months after surgery.. The mean patient age was 46.6 ± 13.1 years, and the mean preoperative body mass index (BMI) was 47.1 ± 18.1. A significant decrease in BMI, weight, waist circumference, fat mass, glucose, LDL cholesterol, total cholesterol, and triglyceride levels was observed after 9 months. Serum basal GLP-1 levels did not change after surgery (0.65 ± 0.18 ng/ml vs. 0.66 ± 0.17 ng/ml; n.s.). Postsurgical correlation analysis showed a negative association between basal GLP-1 and HDL cholesterol (r = -0.57; p < 0.01).. Fasting GLP-1 concentrations did not change after massive weight loss with biliopancreatic diversion in morbidly obese patients without diabetes mellitus.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Risk Factors; Triglycerides; Waist Circumference; Weight Loss

Reductions in mesolimbic responsivity have been noted following Roux-en-Y gastric bypass (RYGB; Ochner et al., 2011a). Given potential for postoperative increases in postprandial gut (satiety) peptides to affect mesolimbic neural responsivity, we hypothesized that: (1) post RYGB changes in mesolimbic responsivity would be greater in the fed relative to the fasted state and; (2) fasted vs. fed state differences in mesolimbic responsivity would be greater post-relative to pre-surgery. fMRI was used to asses neural responsivity to high- and low-calorie food cues in five women 1 mo pre- and 1 mo post-RYGB. Scans were repeated in fasted and fed states. Significant post RYGB decreases in the insula, ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) responsivity were found in the fasted state. These changes were larger than neural changes in the fed state, which were non-significant. Preoperatively, fasted vs. fed differences in neural responsivity were greater in the precuneus, with large but nonsignificant clusters in the vmPFC and dlPFC. Postoperatively, however, no fasted vs. fed differences in neural responsivity were noted. Results were opposite to that predicted and appear inconsistent with the initial hypothesis that postoperative increases in postprandial gut peptides are the primary driver of postoperative changes in neural responsivity.

Topics: Acoustic Stimulation; Adult; Appetite; Cerebral Cortex; Corpus Striatum; Cues; Energy Intake; Fasting; Feeding Behavior; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Magnetic Resonance Imaging; Middle Aged; Models, Neurological; Models, Psychological; Obesity, Morbid; Peptide Fragments; Peptide YY; Photic Stimulation; Postoperative Period; Postprandial Period; Prefrontal Cortex; Reward; Satiety Response; Young Adult

Topics: Adult; Blood Glucose; Fasting; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Ileum; Insulin; Insulin Secretion; Obesity, Morbid; Postgastrectomy Syndromes; Postprandial Period; Recurrence; Reoperation; Secretory Rate

Roux-en-Y gastric bypass (RYGB) imparts long-term weight loss, the mechanisms for which are not well understood. Changes in leptin and gastrointestinal (GI) hormones, including glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin, may contribute to the relative success of RYGB compared with conventional weight loss methods. This study evaluated changes in GI hormones and leptin post-RYGB. The study also evaluated whether GI hormones differed after a short-term dose of protein or fat.. GLP-1, PYY, ghrelin, and leptin were assessed in 16 women before RYGB and up to 1 year after RYGB. Plasma was collected before and at several times after a short-term equicaloric dose of protein or fat.. GLP-1 area under the curve (AUC) increased at week 6 and 1 year in the fat beverage (FAT-BEV) group compared with baseline. PYY AUC remained elevated at 1 year in the FAT-BEV group. Ghrelin AUC decreased at week 2, week 6, and 1 year in the protein beverage (PRO-BEV) group compared with baseline. Ghrelin AUC was lower in the PRO-BEV group compared with the FAT-BEV group at week 6. Fasted leptin decreased at all visits in both groups and was lower in the FAT-BEV group compared with the PRO-BEV group at 1 year.. Changes from baseline were evident for all GI hormones and leptin; some differences were evident soon after surgery (ghrelin, leptin), whereas others were maintained long term (GLP-1, PYY, ghrelin, leptin). In response to a short-term stimulus, protein suppressed ghrelin and fat potently stimulated GLP-1 and PYY. Future work in this area is warranted.

Topics: Adult; Area Under Curve; Dietary Fats; Dietary Proteins; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Weight Loss

Topics: Adolescent; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Humans; Liraglutide; Metformin; Obesity, Morbid; Prader-Willi Syndrome; Treatment Outcome

Direct effects of GLP-1, kinase-mediated, on glucose and lipid metabolism in rat and human extrapancreatic tissues, are amply documented and also changes in type-2 diabetic (T2D) patients. Here, we explored the characteristics of the GLP-1 action and those of its analogs Ex-4 and Ex-9, on muscle glucose transport (GT) and metabolism in human morbid obesity (OB), as compared with normal and T2D subjects. In primary cultured myocytes from OB, GT and glycogen synthase a (GSa) activity values were lower than normal, and comparable to those reported in T2D patients; GT was increased by either GLP-1 or Ex-9 in a more efficient manner than in normal or T2D, up to normal levels; the Ex-4 increasing effect on GSa activity was two times that in normal cells, while Ex-9 failed to modify the enzyme activity. In OB, the control value of all kinases analyzed - PI3K, PKB, MAPKs, and p70s6K - although lower than that in normal or T2D subjects, the cells maintained their response capability to GLP-1, Ex-4, Ex-9 and insulin, with some exceptions. GLP-1 and exendins showed a direct normalizing action in the altered glucose uptake and metabolism in the muscle of obese subjects, which in the case of GLP-1 could account, at least in part, for the reported restoration of the metabolic conditions of these patients after restrictive surgery.

Topics: Adult; Aged, 80 and over; Cells, Cultured; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucose; Humans; Male; Muscle, Skeletal; Obesity, Morbid; Peptide Fragments

Roux-en-Y-Gastric-Bypass (RYGB) reduces overall and diabetes-specific mortality by 40% and over 90%. This study aims to gain insight into the underlying mechanisms of this effect. We evaluated time-courses of glucose, insulin, C-peptide, and the incretin glucagon like peptide-1 (GLP-1) following an oral glucose load. Insulin-sensitivity was measured by a hyperinsulinemic-isoglycemic-clamp-test; glucose-turnover was determined using D-[6,6-(2)H(2)] glucose. Examinations were performed in six nondiabetic patients with excess weight before (PRE: BMI: 49.3 ± 3.2 kg/m(2)) and 7 months after RYGB (POST: BMI: 36.7 ± 2.9 kg/m(2)), in a lean (CON: BMI: 22.6 ± 0.6 kg/m(2)) and an obese control group (CONob) without history of gastrointestinal surgery (BMI: 34.7 ± 1.2 kg/m(2)). RYGB reduced fasting plasma concentrations of insulin and C-peptide (P < 0.01, respectively) whereas fasting glucose concentrations remained unchanged. After RYGB increase of C-peptide concentration following glucose ingestion was significantly higher compared to all other groups (dynamic-area under the curve (Dyn-AUC): 0-90 min: POST: 984 ± 115 ng·min/ml, PRE: 590 ± 67 ng·min/ml, CONob: 440 ± 44 ng·min/ml, CON: 279 ± 22 ng·min/ml, P < 0.01 respectively). Early postprandial increase of glucose concentration was however not affected. GLP-1 concentrations following glucose ingestion were sixfold higher after RYBG than before (P = 0.01). Insulin-stimulated glucose uptake tended to increase postoperatively (M-value: PRE: 1.8 ± 0.5, POST: 3.0 ± 0.3, not significant (n.s.)). Endogenous glucose production (EGP) was unaffected by RYGB. Hepatic insulin resistance index improved after RYGB and was then comparable to both control groups (PRE: 29.2 ± 4.3, POST: 12.6 ± 1.1, P < 0.01). RYGB results in hyper-secretion of insulin and C-peptide, whereas improvements of insulin resistance are minor and seem to occur rather in the liver and the adipose tissue than in the skeletal muscle.

Topics: Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Liver; Male; Obesity, Morbid; Postprandial Period

The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes.. Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined.. In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups.. Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Topics: Diabetes Mellitus, Type 2; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Peptide YY

The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Cells, Cultured; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Insulin Resistance; Mice; Obesity, Morbid; Prospective Studies; Receptors, Glucagon

Bariatric surgery is the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass. Although there is increasing interest in the gut hormone changes after gastric bypass, the long-term changes have not been fully elucidated.. Thirty-four participants were studied cross-sectionally at four different time points, pre-operatively (n = 17) and 12 (n = 6), 18 (n = 5) and 24 months (n = 6) after laparoscopic Roux-en-Y gastric bypass. Another group of patients (n = 6) were studied prospectively (18-24 months). All participants were given a standard 400 kcal meal after a 12-h fast, and plasma levels of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were correlated with changes in appetite over 3 h using visual analogue scores.. The post-operative groups at 12, 18 and 24 months had a higher post-prandial PYY response compared to pre-operative (p < 0.05). This finding was confirmed in the prospective study at 18 and 24 months. There was a trend for increasing GLP-1 response at 18 and 24 months, but this did not reach statistical significance (p = 0.189) in the prospective study. Satiety was significantly reduced in the post-operative groups at 12, 18 and 24 months compared to pre-operative levels (p < 0.05).. Roux-en-Y gastric bypass causes an enhanced gut hormone response and increased satiety following a meal. This response is sustained over a 24-month period and may partly explain why weight loss is maintained.

Topics: Adult; Cross-Sectional Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Prospective Studies; Satiety Response; Weight Loss

To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism.. A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured.. Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold.. Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction.

Topics: Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Enteral Nutrition; Fatty Acids, Nonesterified; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Humans; Incretins; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Postprandial Period

The aim of this study was to evaluate whether gastric bypass with or without vagal preservation resulted in a different outcome.. Body weight, food intake and postprandial peptide YY (PYY) and glucagon-like peptide (GLP-1) levels were compared between gastric bypass (n = 55) and sham-operated rats (n = 27) in three groups. In group 1 (n = 17), the vagal nerve was not preserved, while in group 2 the vagal nerve was preserved during gastric bypass (n = 10). In group 3, gastric bypass rats (n = 28) were randomised for either one of the two techniques.. Rats in which the vagal nerve was preserved during gastric bypass showed a lower body weight (p < 0.001) and reduced food intake (p < 0.001) compared to rats in which the vagal nerve was not preserved during the gastric bypass operation. Levels of PYY and GLP-1 were significantly increased after gastric bypass compared to sham-operated controls (p < 0.05), but there was no difference between gastric bypass rats with and without vagal preservation. Differences in food intake and body weight were not related to the size of the gastro-jejunostomy in gastric bypass rats. There were no signs of malabsorption or inflammation after gastric bypass.. We propose that the vagal nerve should be preserved during the gastric bypass operation as this might play an important role for the mechanisms that induce weight loss and reduce food intake in rats. In contrast, the gastro-jejunal stoma size was found to be of minor relevance.

Topics: Animals; Gastric Bypass; Gastrostomy; Glucagon-Like Peptide 1; Jejunostomy; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Vagus Nerve; Weight Loss

Severe hypoglycemia after Roux-en-Y gastric bypass surgery (RYGB) is an increasingly recognized condition, characterized by neuroglycopenia and inappropriately elevated insulin concentrations that occur primarily in the postprandial state. Both pathophysiology and treatment of this disorder remain elusive, but it has been postulated that hyperplasia and/or hypertrophy of beta-cells due to morbid obesity and/or postsurgical nesidioblastosis may contribute.. The objective of this study was to elucidate the pathophysiology of this condition; specifically, we hypothesized that metabolic abnormalities were a function of altered nutrient transit through the gastrointestinal tract rather than anatomical changes to pancreatic beta-cells that would lead to consistently high insulin secretion irrespective of nutrient transit route. DESIGN/SETTING/SUBJECT/OUTCOME MEASURES: We describe a unique case wherein gastrostomy tube (GT) insertion into the remnant stomach reversed neuroglycopenic symptoms. This subject was admitted to a university hospital research center for standardized measurement of glucose, insulin, and incretin hormones including glucagon-like peptide-1, gastric-inhibitory peptide, and glucagon.. Standardized liquid meal administration via GT vs. oral route demonstrated complete reversal of severe metabolic abnormalities that included hypersecretion of insulin and GLP-1.. Post-RYGB hyperinsulinemia and hypoglycemia result entirely from altered nutrient delivery rather than generalized hyperfunction of beta-cells due to presurgical hypertrophy/hyperfunction or postsurgical nesidioblastosis. These findings support the use of GT for treatment of severe cases and have implications for surgical manipulations that may reverse/prevent this condition.

Topics: Adult; Blood Glucose; Body Mass Index; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Nutritional Status; Obesity, Morbid; Postoperative Complications

The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose.. Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion.. The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of β-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year.. The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.

Topics: Adiponectin; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Secretion; Leptin; Middle Aged; Obesity, Morbid; Postoperative Period; Stomach; Weight Loss

It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery.. Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1+/-2.27 g/m2] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m2) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery).. Insulin levels improved after surgery. T1 was 131.1+/-17.60 pmol/l in the NGT group and 197.57+/-57.94 pmol/l in the AGM group, and T3 was 72.48+/-3.67 pmol/l in the NGT group and 61.2+/-9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06+/-6.18 pmol/l) when compared to the NGT group (22.69+/-4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2.. Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Case-Control Studies; Cohort Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Metabolism Disorders; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Treatment Outcome; Weight Loss

An enlarged incretin response after Roux-en-Y gastric bypass (RYGBP) has been proposed to promote excessive beta-cell function and mass.. The objective of the study was to determine whether RYGBP is associated with a steadily increased glucagon-like peptide 1 (GLP-1) response and a disruption of the relationship between insulin sensitivity and insulin secretion required to maintain plasma glucose in the normal range.. This was a cross-sectional study. Twenty-four women divided into three groups according to time after RYGBP (9-15, 21-30, and more than 36 months). Eight normal-weight and eight morbidly obese women served as controls.. GLP-1 was determined after a standardized test meal. Insulin secretion (AIRg) and insulin sensitivity (S(I)) were derived from an iv glucose tolerance test. Postprandial glucose profile was recorded with a continuous glucose monitoring system.. Area under the curve(0-120) of GLP-1 was larger after RYGBP compared with controls (P < 0.01) but was comparable among surgical groups (P =0.314). Time after surgery was not associated with changes in S(I) (P = 0.657), AIRg (P = 0.329), or the disposition index (DI = AIRgS(I), P = 0.915). After surgery, the GLP-1 response and the DI were not significantly correlated (P = 0.304). Glucose less than 50 mg/dl was found in operated subjects, but the proportion did not increase with time after surgery (P = 0.459). Neither the GLP-1 response (P = 0.620) nor the DI (P = 0.457) differed significantly between those with or without hypoglycemic episodes.. Although the GLP-1 response to meal intake is steadily elevated after RYGBP, this does not result over time in the development of an inappropriate insulin secretion relative to the prevailing insulin sensitivity or the occurrence of hypoglycemic episodes.

Topics: Adult; Area Under Curve; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Islets of Langerhans; Middle Aged; Obesity, Morbid

We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones.. Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp.. Basal GLP1 relative amplitude (amplitude/mesor x 100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 +/- 94 to 846 +/- 161 pmol l(-1) min in NGT, whereas GIP AUC decreased significantly from 1,373 +/- 565 to 513 +/- 186 pmol l(-1) min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD x diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 +/- 3.63 to 36.04 +/- 8.55 micromol [kg fat-free mass](-1) min(-1)) and diabetic patients (from 9.49 +/- 3.56 to 38.57 +/- 4.62 micromol [kg fat-free mass](-1) min(-1)).. An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.

Topics: Adipose Tissue; Adult; Biliopancreatic Diversion; Blood Glucose; Body Mass Index; Circadian Rhythm; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Incretins; Insulin; Insulin Resistance; Middle Aged; Obesity, Morbid

The objective of this study was to quantify hormones that regulate energy and glucose homeostasis to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparoscopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity.. Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied before surgery and at 2, 12, 26 and 52 weeks afterwards.. Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained before surgery and at 26 and 52 weeks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone, free T(4) and free T(3).. At 1 year there was greater weight loss in RYGB compared with LAGB patients (30 vs 15%), but final body mass index was similar (34 vs 33 kg m(-2)). At week 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min after meal were threefold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at week 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin and homeostasis model of assessment (HOMA-IR) decreased in both groups over time but were significantly lower at week 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T(3) (P<0.01) after RYGB.. Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T(3) and leptin.

Topics: Blood Glucose; Female; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Postprandial Period; Prospective Studies; Weight Loss

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.. 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.. 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).. 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.

Topics: Adult; Bariatric Surgery; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Incretins; Obesity, Morbid; Prospective Studies; Time Factors; Treatment Outcome

The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding.. The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal.. Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)).. Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained.. PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect.. RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

Topics: Adult; Bariatric Surgery; Cross-Sectional Studies; Eating; Fasting; Female; Glucagon-Like Peptide 1; Humans; Male; Neurotensin; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Prospective Studies; Protein Precursors; Satiety Response; Weight Loss

Recent physiological knowledge allows the design of bariatric procedures that aim at neuroendocrine changes instead of at restriction and malabsorption. Digestive adaptation is a surgical technique for obesity based in this rationale.. The technique includes a sleeve gastrectomy, an omentectomy and a jejunectomy that leaves initial jejunum and small bowel totaling at least 3 m (still within normal variation of adult human bowel length). Fasting ghrelin and resistin and fasting and postprandial GLP-1 and PYY were measured pre- and postoperatively.. 228 patients with initial body mass index (BMI) varying from 35 to 51 kg/m(2); follow-up: 1 to 5 years; average EBMIL% was 79.7% in the first year; 77.7% in the second year; 71.6% in the third year; 68.9% in the fourth year. PATIENTS present early satiety and major improvement in presurgical comorbidities, especially diabetes. Fasting ghrelin and resistin were significantly reduced (P < 0.05); GLP-1 and PYY response to food ingestion was enhanced (P < 0.05). Surgical complications (4.4%) were resolved without sequela and without mortality. There was neither diarrhea nor detected malabsorption.. Based on physiological and supported by evolutionary data, this procedure creates a proportionally reduced gastrointestinal (GI) tract that amplifies postprandial neuroendocrine responses. It leaves basic GI functions unharmed. It reduces production of ghrelin and resistin and takes more nutrients to be absorbed distally enhancing GLP-1 and PYY secretion. Diabetes was improved significantly without duodenal exclusion. The patients do not present symptoms nor need nutritional support or drug medication because of the procedure, which is safe to perform.

Topics: Adaptation, Physiological; Adult; Aged; Bariatric Surgery; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Humans; Jejunum; Male; Middle Aged; Obesity, Morbid; Omentum; Peptide YY; Resistin

A role of GLP-1 (glucagon-like peptide-1) in the recovery of the metabolic conditions of morbidly obese patients after bariatric surgery has been proposed. Exendin 4 (Ex-4) and exendin 9 (Ex-9) both have GLP-1-like effects upon glucose metabolism in human myocytes. We investigated in normal human adipocytes the effect of GLP-1, Ex-4 and Ex-9, compared with insulin upon the activity of PI3K, PKB, MAPKs and p70s6 kinases, and the participation of these enzymes in their action upon 2-deoxy-D-glucose transport by using potential inhibitors. The study was extended to morbidly obese patients. In normal subjects, GLP-1, Ex-4 and insulin, but not Ex-9, increased glucose uptake. In addition, GLP-1 and Ex-4 stimulated PI3K and MAPKs, similar to insulin, but not PKB. Ex-9 only enhanced PI3K, while none affected p70s6k. Inhibition of both PI3K and MAPKs blocked the stimulatory action of GLP-1, Ex-4 and insulin upon glucose transport. In obese patients, basal PI3K, PKB and MAPK activity was, as a rule, lower than that in normal subjects, while cells maintained their normal incremental response to GLP-1, Ex-4 or insulin; Ex-9 induced a clear stimulation of p42 MAPK. In summary, in normal human adipocytes, GLP-1 and Ex-4 have a protein kinase-dependent increasing effect upon glucose transport, which is impaired in obese patients. The participation of GLP-1 in the normalization of the metabolic conditions of the obese may occur through its effects on lipid metabolism or through effects upon glucose transport and/or metabolism in the liver and muscle, which in human obesity remain to be investigated.

Topics: Adipocytes; Adult; Biological Transport; Cells, Cultured; Deoxyglucose; Exenatide; Female; Glucagon-Like Peptide 1; Glucose; Humans; Male; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptides; Phosphotransferases; Venoms

Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth.. We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts.. Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients.. A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Eating; Female; Food; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Incretins; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Obesity, Morbid; Postoperative Complications

Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are cosecreted in the same enteroendocrine L-cells of the gut and reported to inhibit food intake additively. However, findings in human studies regarding these peptides are controversial. The aim of this study was to analyze the relationships between fasting PYY, GLP-1, and weight status in morbidly obese patients before and after surgically induced weight loss.. Fasting GLP-1, PYY, glucose, and insulin concentrations; blood pressure; and body-mass index (BMI) were determined in 30 morbidly obese adults (mean BMI 45.8, mean age 40 years) before bariatric surgery [Roux-en-Y gastric bypass (RYGB): n = 19; gastric banding (GB): n = 11] and after weight loss (mean 50% excess weight loss) in the course of mean 2 years.. GLP-1 concentrations decreased (mean -20 pg/ml; mean -38%; p = 0.001) and PYY concentrations increased (mean +19 pg/ml; mean +19%, p = 0.036) after bariatric surgery. The weight loss and changes of GLP-1 were significantly (p < 0.05) more pronounced after RYGB as compared to GB, whereas the changes of PYY did not differ significantly between the patients who had undergone RYGB or GB.. In morbidly obese adults reducing their weight by bariatric surgery, fasting PYY levels increased and GLP-1 concentrations decreased independently of each other. Therefore, the relationship between PYY and GLP-1 seems more complicated than might be anticipated from animal and in vitro studies.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Radioimmunoassay; Statistics, Nonparametric; Weight Loss

The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood.. The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety.. This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 +/- 6.1 kg/m(2)] before and 6 wk after RYGBP.. Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 +/- 7.8 kg/m(2)), the area under the curve(0-120') of GLP-1 and of PYY in response to the standardized test meal were significantly elevated (P < 0.05 and P < 0.01, respectively). These hormonal responses were significantly larger (P < 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery. The 2.9 +/- 1.2- and 1.6 +/- 1.9-fold increase, respectively, in the area under the curve(0-120') of GLP-1 and PYY were accompanied by a significant decrease in fasting (P < 0.05) and postprandial hunger (P = 0.05) and a significant increase in satiety (P < 0.05) after meal intake. Nevertheless, a significant correlation between changes in the hormonal and eating behavior parameters was not found.. Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquid-meal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP.

Topics: Adult; Eating; Female; Gastric Bypass; Gastric Emptying; Gastrointestinal Transit; Glucagon-Like Peptide 1; Humans; Hunger; Male; Obesity, Morbid; Peptide YY; Prospective Studies; Satiety Response

Topics: Animals; Cell Proliferation; Comorbidity; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hyperinsulinism; Hyperplasia; Hypertrophy; Hypoglycemia; Incidence; Insulin; Insulin Secretion; Insulin-Secreting Cells; Nesidioblastosis; Obesity, Morbid; Postoperative Complications; Rats

It has been proposed, that the dramatic amelioration of type 2 diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However, human data supporting this hypothesis is scarce.. A 12-month prospective study on the changes in glucose homeostasis, and active GLP-1 in response to a standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1+/-1.0 kg/m(2)) who had different degrees of glucose tolerance: normal glucose tolerance (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10).. At 6 weeks after RYGBP, despite the subjects still being markedly obese (BMI 43.5+/-0.9 kg/m(2)), fasting plasma glucose and HbA1c decreased in the 3 study groups (P<0.05). Insulin sensitivity improved, but was still abnormal in a comparable proportion of subjects among groups (P=0.717). When insulin secretion was accounted for the prevailing insulin sensitivity, an increase was found in subjects with diabetes (P<0.05) although it remained lower compared to NGT- and IGT-subjects (P<0.01). At 12 months follow-up, no differences among groups were found in the evaluated glucose homeostasis parameters. Compared to baseline, at 6 weeks the incremental AUC(0-120') of active GLP-1 in response to the STM increased in NGT and IGT (P<0.05) but not in subjects with diabetes (P=0.285). However, the GLP-1 response to a STM was comparable among groups at 12 months follow-up (P=0.887).. 1) RYGBP was associated with an improvement but not complete restoration of glucose homeostasis at 6 weeks after surgery. 2) GLP-1 is not a critical factor for the early changes in glucose tolerance.

Topics: Adult; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Time Factors; Treatment Outcome; Weight Loss

Bariatric operations promote weight loss and improve glucose homeostasis. Glucagon-like peptide-1 (GLP-1) is considered as a possible mediator of the antidiabetic effects of such operations.. The present study aimed to gain information on the time course for changes in glucose tolerance, as well as insulin, glucagon and GLP-1 secretion, during an oral glucose tolerance test (OGTT), in 31 obese patients examined 1, 3 and 6 months after Larrad's biliopancreatic diversion (BPD) or 6 months after vertical banded gastroplasty (VBG).. A time-related progressive decrease in body weight coincided with lowering of plasma triglycerides, decrease of basal plasma glucose and its incremental area during OGTT, and reduction of basal plasma insulin together with an increase of its incremental area. The time-related decrease of plasma glucagon during OGTT was comparable before and after surgery. Both the basal plasma GLP-1 concentration and its incremental area during the OGTT increased strikingly after surgery, a steady-state situation being reached 3 months after surgery. The most striking differences between the somewhat older and less glucose-tolerant subjects of VBG compared to BPD after surgery, consisted in a decrease in cholesterol and LDL only observed in BPD and a much more pronounced increase in basal and incremental plasma GLP-1 in BPD. GLP-1, like glucagon, increased lipolysis, but failed to duplicate the lipogenetic action of insulin in isolated adipocytes obtained at the time of surgery.. These findings support the postulated role of GLP-1, secreted by the hindgut, as a key mediator of the antidiabetic effects of bariatric operations.

Topics: Adipocytes; Adult; Age Factors; Bariatrics; Biliopancreatic Diversion; Blood Glucose; Cholesterol; Cholesterol, LDL; Female; Follow-Up Studies; Gastroplasty; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Lipolysis; Male; Obesity, Morbid; Peptide Fragments; Protein Precursors; Triglycerides; Weight Loss

Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5 male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height 158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/- 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.

Topics: Adult; Anastomosis, Roux-en-Y; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Obesity, Morbid; Peptide Fragments; Protein Precursors

A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation.. This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level.. Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal-related response of CCK and somatostatin and basal levels of GLP-1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01).. Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro-hormone changes.

Topics: Adult; Cholecystokinin; Electric Stimulation Therapy; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Leptin; Male; Obesity, Morbid; Peptides; Satiation; Somatostatin; Stomach; Weight Loss

The aim of the present study was to study the interdigestive motor complex (MMC), distal small intestinal hormones, and gastric emptying in normal-weight and obese subjects before and after jejunoileal bypass (JIB). Therefore, fasting antroduodenal motility, gastric emptying, and RIA for motilin (MOT), neurotensin (NT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) was performed in nine obese subjects before (BMI 42 +/- 4 kg/m2) and nine months after (BMI 31 +/- 4) JIB, and in two groups of nine age- and sex-matched controls (BMI 23 +/- 1 and 21 +/- 1). The rate of gastric emptying was faster in obese subjects and GLP-1 lower compared to normal-weight controls. After JIB, fewer phase III of the MMC were observed; fasting levels of PYY were elevated during the MMC; postprandial levels of NT, PYY, and GLP-1 were elevated; and gastric emptying was delayed. Our results suggest that there may be an association between an impaired GLP-1 response after food intake and obesity, and after JIB, PYY seems to regulate interdigestive motility while GLP-1 may regulate early gastric emptying.

Topics: Adolescent; Adult; Female; Gastric Emptying; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon-Like Peptide 1; Humans; Male; Myoelectric Complex, Migrating; Obesity, Morbid; Peptides; Postprandial Period

Some studies have shown a more rapid gastric emptying in obese subjects. Six to twelve months after jejunoileal bypass (JIB) neurotensin (NT) and enteroglucagon have been shown to be elevated after food intake. These hormones, together with peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) have been implicated in the reduction of upper gastrointestinal motility seen after infusion of nutrients into the ileum.. To study if the postprandial gut hormone pattern and gastric emptying is altered 20 y after JIB.. Seven subjects operated with JIB a mean (s.d.) 20 +/- 3 y ago, with a BMI of 44 +/- 4 kg/m2 at the time of surgery and 31 +/- 4 at present. For comparison seven sex-matched non-operated obese controls (BMI 43 +/- 3) were studied.. Serial blood samples were obtained every 10 min after intake of a 280 kcal meal. Radioimmunoassays for motilin, cholecystokinin (CCK), NT, PYY and GLP-1 were performed. Gastric emptying of a solid meal was studied using a radioactively labelled omelette (of 310 kcal) for 120 min).. After JIB postprandial motilin, CCK, NT, PYY and GLP-1 were elevated compared to non-operated obese subjects. Similarly, basal levels of CCK, motilin, GLP-1 and PYY were elevated in the operated group. No difference was observed in the rate of gastric emptying between the two groups.. Both fasting and postprandial gut hormone levels are elevated 20 y after JIB. The impact of long-term rapid stimulation of the ileum and subsequent raised gut hormone levels on gastric emptying is not clear.

Topics: Cholecystokinin; Female; Follow-Up Studies; Gastric Emptying; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Jejunoileal Bypass; Male; Middle Aged; Motilin; Neurotensin; Obesity, Morbid; Peptide YY; Peptides; Postprandial Period; Time Factors