Dimitrios J. Pournaras

Remission of Type 2 Diabetes After Gastric Bypass and Banding: Mechanisms and 2 Year Outcomes

Objective: To investigate the rate of type 2 diabetes remission after gastric bypass and banding and establish the mechanism leading to remission of type 2 diabetes after bariatric surgery. Summary Background Data: Glycemic control in type 2 diabetic patients is improved after bariatric surgery. Methods: In study 1, 34 obese type 2 diabetic patients undergoing either gastric bypass or gastric banding were followed up for 36 months. Remission of diabetes was defined as patients not requiring hypoglycemic medication, fasting glucose below 7 mmol/L, 2 hour glucose after oral glucose tolerance test below 11.1 mmol/L, and glycated haemoglobin (HbA1c) <6%. In study 2, 41 obese type 2 diabetic patients undergoing either bypass, banding, or very low calorie diet were followed up for 42 days. Insulin resistance (HOMA-IR), insulin production, and glucagon-like peptide 1 (GLP-1) responses after a standard meal were measured. Results: In study 1, HbA1c as a marker of glycemic control improved by 2.9% after gastric bypass and 1.9% after gastric banding at latest follow-up (P < 0.001 for both groups). Despite similar weight loss, 72% (16/22) of bypass and 17% (2/12) of banding patients (P = 0.001) fulfilled the definition of remission at latest follow-up. In study 2, within days, only bypass patients had improved insulin resistance, insulin production, and GLP-1 responses (all P < 0.05). Conclusions: With gastric bypass, type 2 diabetes can be improved and even rapidly put into a state of remission irrespective of weight loss. Improved insulin resistance within the first week after surgery remains unexplained, but increased insulin production in the first week after surgery may be explained by the enhanced postprandial GLP-1 responses.

Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders.

The American Diabetes Association recently defined remission of type II diabetes as a return to normal measures of glucose metabolism (haemoglobin (Hb) A1c below 6 per cent, fasting glucose less than 5·6 mmol/l) at least 1 year after bariatric surgery without hypoglycaemic medication. A previously used common definition was: being off diabetes medication with normal fasting blood glucose level or HbA1c below 6 per cent. This study evaluated the proportion of patients achieving complete remission of type II diabetes following bariatric surgery according to these definitions.

Obesity, Gut Hormones, and Bariatric Surgery

Obesity is becoming the healthcare epidemic of this century. Bariatric surgery is the only effective treatment for morbid obesity. Gut hormones are key players in the metabolic mechanisms causing obesity. In this review we explore the role of these hormones as facilitators of appetite control and weight loss after bariatric surgery, and we describe the now established gut–brain axis.

After bariatric surgery, what vitamins should be measured and what supplements should be given?

Bariatric surgery is the most effective treatment for morbid obesity. Although calorie malabsorption does not occur in most bariatric procedures, micronutrient deficiencies are possible. Multivitamin supplementation is essential following bariatric surgery. The recommendation would be to screen for multivitamin deficiencies prior to surgery and to monitor vitamin levels postoperatively at regular intervals. In this paper, we review the data for screening and supplementation after bariatric procedures for different vitamins.

Ghrelin and metabolic surgery.

Metabolic surgery is the most effective treatment for morbid obesity. Ghrelin has been implicated to play a role in the success of these procedures. Furthermore, these operations have been used to study the gut-brain axis. This article explores this interaction, reviewing the available data on changes in ghrelin levels after different surgical procedures.

The effect of bariatric surgery on gut hormones that alter appetite

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.

Are Bile Acids the New Gut Hormones? Lessons From Weight Loss Surgery Models

Bileacidsareincreasinglyrecognizedasmoleculeswith endocrine functions (1), but their effect on gut hormones, energy expenditure, and insulin sensitivity has not been fully elucidated. Bile acids do represent an attractive target for obesity and type 2 diabetes from a therapeutic pointofviewbecauseoftheendogenouschangesobserved after gastric bypass (2). The anatomical changes with alteredbileflowaftergastricbypasssurgerymakestudieson animal models such as the one by Kohli et al (2) extremely relevant.Gastricbypasssurgeryhasbeenshowntobesafe and effective for inducing weight loss and ameliorating hyperglycemia, but understanding the mechanism of action and dissecting the role of bile acid manipulation in particular, not only offers important insight into glucose metabolism, but also may open the door for even more effectivetreatmentoptionsfortype2diabetesandobesity. These therapies could be medical, surgical, endoscopic, and perhaps more importantly combinational therapy. ThestudybyKohlietal(2)demonstratesthemetabolic effect of diverting bile to the distal gut. The authors used aninnovativeapproachbyplacingacatheterintothecommon bile duct of male obese rats to drain bile to the more distal jejunum. Bile diversion was associated with increased serum bile acids, enhanced postprandial glucagon-like peptide-1 response, improved glucose tolerance, and reduced hepatic steatosis. None of these effects were observed in the appropriate sham group. By isolating the effect of the altered bile flow without changing the length of the gut and the size of the stomach, this work suggests that the metabolic effects of gastric bypass cannot be explained by weight loss alone. Consistent with the work of Kohlietal(2)inanotherratmodel,itwasalsoshownthat drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight (3). Kohli et al advanced our current knowledge by demonstrating that manipulating bile flow without altering the anatomy of the small bowel leads to improved glucose tolerance. During the last decade, the role of gut hormones after gastric bypass surgery has featured prominently (4), but it hasalsobecomeevidentthatguthormonesdonotexplain alltheeffectsseenafterweightlosssurgery.Forone,when gut hormones are blocked with a somatostatin analog, a substantial increase in ad libitum food intake is observed, but food intake does not return to presurgical levels (5). Second,manyofthebeneficialchangesinglycemiccontrol occur even after open gastric bypass surgery (6), which is associated with increased inflammation and should have

Techniques, assessment, and effectiveness of bariatric surgery in combating obesity

Correspondence: Carel w Le Roux imperial weight Centre, Department of investigative Medicine, imperial College London, London w6 8RF, UK Tel +44 20 3313 0532 Fax +44 20 3313 0673 email c.leroux@imperial.ac.uk Abstract: Obesity is an epidemic disease, and its prevalence is predicted to rise in the future. Many health and social comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, cancer, nonalcoholic fatty liver disease, arthritis, infertility, eating disorders, unemployment, and low quality of life, have been associated with obesity. Nowadays, bariatric surgery is the only effective treatment for severe obesity. An increasing body of literature demonstrates significant remission of obesity-related comorbidities and an increase in life expectancy after surgical treatment. Unfortunately, serious complications can appear after surgery, and the careful preoperative assessment of patients is necessary to estimate the indications and contraindications of bariatric surgery. Recent studies report the lower complication and mortality rates when bariatric procedures are performed in high-volume centers. The purpose of this review is to describe the techniques of the currently used surgical procedures and the clinical effectiveness of bariatric surgery. Additionally, the possible complications and mortality rates after bariatric surgery are discussed.

Preventing Type 2 Diabetes, CVD, and Mortality: Surgical Versus Non-surgical Weight Loss Strategies

The burden of type 2 diabetes is increasing. The prevention of the disease, improvement of metabolic control, and more importantly reduction in mortality remain a challenge for primary care doctors, diabetologists, researchers and policymakers. In this article, the available literature is reviewed with a focus on recent developments. Comparison between medical and surgical interventions is performed using mainly head-to-head trials where possible. Weight loss surgery is effective for glycaemic control. The need for level 1 data with hard end points such as cardiovascular risk and mortality is highlighted, and the prospect of the combination of existing therapy options is emphasized.

Bypass of the Proximal Gut Has Weight Loss Independent Effects on Glycemic Control

Introduction The reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism in focus. We aimed to explore the role of the proximal gut on glucose handling.Methods A comparative controlled investigation of oral versus gastrostomy glucose loading in patients who had previously undergone gastric bypass and had a gastrostomy tube in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or via the gastrostomy tube (day 2). Plasma levels of glucose, insulin, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were measured pre and post glucose loading. Results Exclusion of the proximal small gut from glucose passage induced lower plasma glucose responses and higher plasma insulin, GLP-1 and PYY responses compared to glucose via a gastrostomy (p<0.05). Conclusions Exclusion of glucose passage through the proximal small gut results in enhanced insulin and gut hormone responses and suggests a weight loss independent effect explaining the improved glycaemic control after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies.