What is the role of bariatric surgery in the management of obesity?

Diet, exercise, cognitive behavioral therapy and pharmacotherapy are some of the means of assisting patients to lose weight, with bariatric surgery being the most effective. Over the last two decades, the increased awareness of the systemic benefits of bariatric surgery, as well as the improved safety and the wider use of the laparoscopic approach, has made bariatric surgery flourish. In the United Kingdom, the adjustable gastric band (10%), vertical sleeve gastrectomy (37%) and Roux-en-Y gastric bypass (45%) are the three most common procedures. Obesity-associated mortality and co-morbidities such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, renal dysfunction and depression improve significantly with bariatric surgery. The mechanisms of weight loss extend beyond restriction and malabsorption and include changes in hunger and satiety, food preferences, and possibly energy expenditure. Despite its safety and efficacy, bariatric surgery is underutilized as less than 1% of adults with obesity receive it. In view of the evolution of obesity into a global threat, access to bariatric surgery should be increased, whilst developing safer and less invasive weight loss treatments.

Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of ß-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Application of the International Diabetes Federation and American Diabetes Association criteria in the assessment of metabolic control after bariatric surgery.

The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) have introduced specific criteria to define the 'optimization' of the metabolic state and glycaemic 'remission' of type 2 diabetes mellitus (T2DM) after bariatric surgery, respectively. Our objective was to assess the percentage of patients achieving these criteria. Data were collected for body mass index, glycaemic markers, lipids, blood pressure, hypoglycaemia and medication usage from 396 morbidly obese T2DM patients who underwent bariatric surgery in two centres and followed up for 2 years. At year 1, 14% of patients achieved the IDF criteria and 38% the ADA criteria, whereas at 2 years 8 and 9% satisfied these criteria, respectively. A relatively low proportion of patients achieved optimization of the metabolic state and T2DM remission. These patients may potentially benefit from the combination of bariatric surgery and adjuvant medical therapy to achieve optimal metabolic outcomes.

A holistic assessment of bariatric surgical outcomes in a Northern Irish cohort.

The King's Obesity Staging system was developed to evaluate the effect of obesity treatments in multiple physical, psychological and functional domains. In this prospective cohort study, a Northern Irish cohort was scored using the King's Obesity Staging system before and 1 year after bariatric surgery. 71 individuals underwent surgery and 31 (44%) had type 2 diabetes. Bariatric surgery improved each health domain (p < 0.05). A subgroup with type 2 diabetes showed a significantly greater improvement in gonadal disease (polycystic ovarian syndrome and sub-fertility) (p = 0.02), and a trend towards greater improvement in cardiovascular disease (p = 0.07) compared with the non-diabetic subgroup. Half of those with pre-diabetes were normoglycaemic postoperatively (p < 0.05). The King's Obesity Staging system can be used to holistically evaluate the outcomes of bariatric surgery. Patients benefit from bariatric surgery in many ways, but those with diabetes may benefit more.

Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass.

BACKGROUND: Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown. METHODS: The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg(-1)), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg(-1)) and somatostatin analogue octreotide (10 µg kg(-1)) on feeding and BW were evaluated in rats after gastric bypass. RESULTS: Gastric bypass rats weighed (P<0.01) and ate less on postoperative day 5 (P<0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (P<0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P=0.02 and P<0.0001, respectively). Similar reduction in food intake was observed in sham rats (P=0.02 and P<0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P=0.03) and sham rats (P=0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P=0.007), but not in sham rats (P=0.87). CONCLUSION: Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Proximal jejunal stoma as ultima ratio in case of traumatic distal duodenal perforation facilitating successful EndoVAC® treatment: A case report.

INTRODUCTION: During damage control surgery for blunt abdominal traumata simultaneous duodenal perforations can be missed making secondary sufficient surgical treatment challenging. Endoluminal vacuum (EndoVAC™) therapy has been shown to be a revolutionary option but has anatomical and technical limits. PRESENTATION OF THE CASE: A 59-year old man with hemorrhagic shock due to rupture of the mesenteric root after blunt abdominal trauma received damage control treatment. Within a scheduled second-look, perforation of the posterior duodenal wall was identified. Due to local and systemic conditions, further surgical treatment was limited. Decision for endoscopic treatment was made but proved to be difficult due to the distal location. Finally, double-barreled jejunal stoma was created for transstomal EndoVAC™ treatment. Complete leakage healing was achieved and jejunostomy reversal followed subsequently. DISCUSSION: During damage control surgery simultaneous bowel injuries can be missed leading to life-threatening complications with limited surgical options. EndoVAC™ treatment is an option for gastrointestinal perforations but has anatomical limitations that can be sufficiently shifted by a transstomal approach for intestinal leakage. CONCLUSION: In trauma related laparotomy complete mobilization of the duodenum is crucial. As ultima ratio, transstomal EndoVAC™ is a safe and feasible option and can be considered for similar cases.

Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea.

SUMMARY: Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. LEARNING POINTS: Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.

Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans.

OBJECTIVE: Unlike gastric banding or sleeve gastrectomy procedures, intestinal bypass procedures, Roux-en-Y gastric bypass in particular, lead to rapid improvements in glycaemia early after surgery. The bypass of the proximal small bowel may have weight loss and even caloric restriction-independent glucose-lowering properties on hepatic insulin sensitivity. In this first human mechanistic study, we examined this hypothesis by investigating the early effects of the duodeno-jejunal bypass liner (DJBL; GI Dynamics, USA) on the hepatic insulin sensitivity by using the gold standard euglycaemic hyperinsulinaemic clamp methodology. METHOD: Seven patients with obesity underwent measurement of hepatic insulin sensitivity at baseline, 1 week after a low-calorie liquid diet and after a further 1 week following insertion of the DJBL whilst on the same diet. RESULTS: Duodeno-jejunal bypass liner did not improve the insulin sensitivity of hepatic glucose production beyond the improvements achieved with caloric restriction. CONCLUSIONS: Caloric restriction may be the predominant driver of early increases in hepatic insulin sensitivity after the endoscopic bypass of the proximal small bowel. The same mechanism may be at play after Roux-en-Y gastric bypass and explain, at least in part, the rapid improvements in glycaemia.

Psychological characteristics, eating behavior, and quality of life assessment of obese patients undergoing weight loss interventions.

BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment for obesity. However, not all patients have similar weight loss following surgery and many researchers have attributed this to different pre-operative psychological, eating behavior, or quality-of-life factors. The aim of this study was to determine whether there are any differences in these factors between patients electing to have bariatric surgery compared to less invasive non-surgical weight loss treatments, between patients choosing a particular bariatric surgery procedure, and to identify whether these factors predict weight loss after bariatric surgery. MATERIAL AND METHODS: This was a prospective study of 90 patients undergoing gastric bypass, vertical sleeve gastrectomy, or adjustable gastric banding and 36 patients undergoing pharmacotherapy or lifestyle interventions. All patients completed seven multi-factorial psychological, eating behavior, and quality-of-life questionnaires prior to choosing their weight loss treatment. Questionnaire scores, baseline body mass index, and percent weight loss at 1 year after surgical interventions were recorded. RESULTS AND CONCLUSIONS: Surgical patients were younger, had a higher body mass index, and obesity had a higher impact on their quality of life than on non-surgical patients, but they did not differ in the majority of eating behavior and psychological parameters studied. Patients opting for adjustable gastric banding surgery were more anxious, depressed, and had more problems with energy levels than those choosing vertical sleeve gastrectomy, and more work problems compared to those undergoing gastric bypass. Weight loss after bariatric surgery was predicted by pre-operative scores of dietary restraint, disinhibition, and pre-surgery energy levels. The results of this study generate a number of hypotheses that can be explored in future studies and accelerate the development of personalized weight loss treatments.

Influence of diabetes surgery on gut hormones and incretins.

The dramatic rise in the prevalence of obesity and type 2 diabetes mellitus (T2DM) has become a major global public health issue. There is increasing evidence that metabolic surgery is more effective than diet and exercise for diabetes remission and weight loss. Moreover, the rapid time course and disproportional degree of T2DM improvement after metabolic procedures compared with equivalent weight loss with conservative treatment, suggest surgery-specific, weight-independent effects on glucose homeostasis. Gut hormones has been proposed as one of the potential mechanisms for the weight-independent diabetes remission and long-term weight loss after these procedures. In this review we discuss the available current metabolic procedures and we review the current human data on changes in gut hormones after each metabolic procedure.

El espectacular aumento de la prevalencia de la obesidad y la diabetes mellitus tipo 2 (DMT2) se ha convertido en un importante problema de salud pública mundial. Hay evidencias crecientes de que la cirugía metabólica es más eficaz que la dieta y el ejercicio para remisión de la diabetes y la pérdida de peso. Por otra parte, el inmediato y elevado grado de mejora de la DM2 tras los procedimientos metabólicos en comparación con la equivalente pérdida de peso mediante el tratamiento conservador, sugieren efectos específicos de la cirugía, peso-independientes en la homeostasis de la glucosa. Se han propuesto a las hormonas intestinales como uno de los posibles mecanismos para la remisión de la diabetes peso-independiente y la pérdida de peso a largo plazo la después de estos procedimientos. En esta revisión se discuten los procedimientos metabólicos actuales disponibles y se revisan los datos humanos actuales sobre los cambios en las hormonas intestinales después de cada procedimiento metabólico.

Alterations of sucrose preference after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass.