Bariatric Times

FEB 2018

A peer-reviewed, evidence-based journal that promotes clinical development and metabolic insights in total bariatric patient care for the healthcare professional

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Review 13 Bariatric Times • February 2018 The Role of Bariatric Surgery to Treat Diabetes: Current Challenges and Perspectives by CHRYSI KOLIAKI, STAVROS LIATISE, CAREL W. LE ROUX, and ALEXANDER KOKKINOS BMC Endocr Disord. 2017;17(1):50. ABSTRACT Bariatric surgery is emerging as a powerful weapon against severe obesity and type 2 diabetes mellitus (T2DM). Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to treat T2DM, especially in light of accumulating evidence that surgery with gastrointestinal manipulations results in T2DM remission (metabolic surgery). The major mechanisms mediating the weight loss-independent effects of bariatric surgery comprise effects on tissue-specific insulin sensitivity, ß-cell function and incretin responses, changes in bile acid composition and flow, modifications of gut microbiota, intestinal glucose metabolism, and increased brown adipose tissue metabolic activity. Shorter T2DM duration, better preoperative glycemic control, and profound weight loss have been associated with higher rates of T2DM remission and lower risk of relapse. In the short and medium term, a significant amount of weight is lost, T2DM might completely regress, and cardiometabolic risk factors are dramatically improved. In the long term, metabolic surgery can result in durable weight loss, prevent T2DM and cancer, improve overall glycemic control while leading to significant rates of T2DM remission, and reduce total and cause-specific mortality. The gradient of efficacy for weight loss and T2DM remission comparing the four established surgical procedures is biliopancreatic diversion > Roux-en-Y gastric bypass > sleeve gastrectomy > laparoscopic adjustable gastric banding. According to recently released guidelines, bariatric surgery should be recommended in patients with diabetes with class III obesity, regardless of their level of glycemic control, and patients with class II obesity with inadequately controlled T2DM despite lifestyle and optimal medical therapy. Surgery should also be considered in patients with class I obesity and inadequately controlled hyperglycemia despite optimal medical treatment. KEYWORDS Metabolic surgery, bariatric surgery, obesity, type 2 diabetes mellitus, diabetes remission BACKGROUND Type 2 diabetes mellitus (T2DM) is associated with obesity and multiple metabolic derangements, leading to increased morbidity, mortality, and financial burden. Although population-based efforts through lifestyle interventions are essential to prevent and deal with the parallel epidemics of obesity and T2DM, few patients who have already developed T2DM and obesity are able to adhere to and accomplish long-term weight loss and glycemic control. 1 Given its role in metabolic regulation, the gastrointestinal tract constitutes a biologically and clinically meaningful target to treat T2DM, especially in light of accumulating experimental and clinical evidence that surgery with gastrointestinal manipulations might result in T2DM remission. 2 Surgical operations with intestinal diversion and mainly duodenal-jejunal exclusion have consistently shown beneficial effects on glucose homeostasis by reducing insulin resistance and increasing insulin secretion. 3 Mechanistic evidence further suggests that the bypass or exclusion of the duodenum and jejunum (proximal gut) might exert direct beneficial effects on glycemic control beyond those mediated by weight loss. 4 The widely used term metabolic surgery applies to those types of weight loss surgery modalities involving an anatomical bypass of the upper gastrointestinal tract and a functional remodeling of the intestine, which has been shown to confer the most important benefits with regard to glucose homeostasis. 3 In a systematic review and meta- analysis of 11 randomized clinical trials (RCTs) comparing surgical to nonsurgical treatment of morbid obesity, bariatric surgery was associated with greater weight loss, higher remission rates of T2DM and metabolic syndrome, better lipid profiles, greater improvement in quality of life, and substantial reductions in medication requirements. 5 Furthermore, a growing number of recent RCTs in patients with T2DM that mainly included individuals with a body mass index (BMI) 35kg/m 2 or greater have consistently demonstrated superior efficacy of bariatric surgery in reducing weight and lowering glycemia, compared to a variety of medical and lifestyle interventions. 6–13 The aim of this review is to discuss the major pathophysiological mechanisms mediating weight loss and T2DM remission after bariatric surgery, summarize the clinical and biological predictors of T2DM remission after surgery, and provide an update on the short-, mid- and long-term effects of bariatric surgery in patients with obesity and T2DM, with a focus on weight loss durability, T2DM remission, improvement of cardiovascular risk factors, diabetes- related complications, mortality, and survival. Recent recommendations concerning the role of bariatric surgery in the treatment algorithm of patients with T2DM are critically appraised, whereas controversial issues and knowledge gaps are further discussed. DESCRIPTION OF SURGICAL PROCEDURES AND THEIR RATIONALE The major distinction between bariatric procedures relies on their mechanisms of action and comprises purely restrictive, malabsorptive, or combination techniques. Of note, the length of the upper gastrointestinal tract bypass is thought to play a major role in determining the magnitude of weight loss and metabolic outcomes. 14 Among various techniques, the following four are the most studied in terms of safety and efficacy to promote weight loss and improve metabolic state and overall health (Figure 1). Laparoscopic adjustable gastric banding (LAGB) involves encircling the upper part of the stomach with a silicone adjustable band with an inflatable balloon at the inner surface connected with a port placed subcutaneously, through which pressure on the vagal afferent intraganglionic laminar endings (IGLEs) can be adjusted by adding or retracting fluid (Figure 1a). FIGURE 1. Graphical presentation of the four best established and standardized types of bariatric surgery—A) Laparoscopic adjustable gastric banding, B) Roux-en-y gastric bypass, C) Vertical sleeve gastrectomy and D) Biliopancreatic diversion

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