title: Neuro-modulation and bariatric surgery for type 2 diabetes mellitus.
abstract: Obesity has reached epidemic proportions and is continuing to grow into one of the leading healthcare issues worldwide. With this development, bariatric surgery has emerged as an acceptable treatment for morbid obesity, generally achieving meaningful and sustained weight loss. In a surprising turn of events, bariatric surgery was also found to be the most effective therapy for type 2 diabetes mellitus (T2DM). This observation has sparked a great deal of research that has improved our understanding of T2DM pathophysiology; it has facilitated the development of medical treatment and is expanding the indications for bariatric surgery. It was traditionally accepted that bariatric surgery causes weight loss by restriction of gastric volume, intestinal malabsorption, or a combination of the two. Laparoscopic adjustable gastric banding (LAGB) is considered a purely restrictive procedure that involves the placement of an adjustable band around the cardia of the stomach, creating a 15 ml pouch. Laparoscopic sleeve gastrectomy (LSG) is the resection of the fundus all along the greater curvature of the stomach. LSG was once considered a restrictive procedure, but this presumption has recently come under scrutiny. Bilio-pancreatic diversion (BPD) is an example of a procedure that was considered predominantly malabsorptive. In this operation, the ingested nutrients are diverted from the stomach to the ileum, bypassing a large segment of proximal bowel. Roux-en-Y gastric bypass (RYGB) traditionally combines both mechanisms, partitioning a small pouch from the proximal stomach and diverting the ingested nutrients to the jejunum with a roux-en-Y gastro-jejunostomy. However, recent investigation suggests additional mechanisms of action including hormonal. Today, RYGB is the procedure of choice for morbidly obese patients. The effect of bariatric surgery on T2DM was initially described in 1995 by Pories et al., who reported that there was an overall T2DM resolution after RYGB of 82.9% (1). A resolution rate of approximately 80% has been demonstrated repeatedly (2,3). The initial assumption was that the mechanism causing this effect was through weight loss. It is becoming evident that the anti-diabetic effect is not entirely weight loss as there is a consistent observation that the improvement of glucose and insulin levels occurs within days after RYGB, clearly too soon to be due to the weight loss (1,4). The ensuing body of literature has generated two leading theories attempting to explain this weight-independent anti-diabetic effect after RYGB. The 'hindgut' proposes that rapid delivery of partially digested nutrients to the distal bowel up-regulates the secretion of incretins such as glucagon-like peptide-1 (GLP-1). The result of the increased incretin secretion is an enhanced glucose-dependent insulin secretion, as well as a number of other changes causing improved glucose tolerance (4). In the second theory, 'the foregut hypothesis', the exclusion of the duodenum results in the inhibition of a 'putative' signal that is responsible for insulin resistance (IR) and/or abnormal glycaemic control. In a non-obese diabetic rat model, surgical diversion of the proximal bowel caused rapid improvement of diabetes without reduction of food intake or change in weight (5). Many aspects regarding surgical treatment of T2DM are still questionable and unexplained. Emerging data are starting to clarify the mechanisms participating in the anti-diabetic effect, and also challenging long-held theories.
authors.affiliation: Department of Surgery, Tufts Medical Center, Boston, MA, USA. dspector@tuftsmedicalcenter.org
authors.forename: D
authors.initials: D
authors.lastname: Spector
authors.forename: S
authors.initials: S
authors.lastname: Shikora
mesh_terms: D000818:Animals; D050110:Bariatric Surgery; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000601:surgery*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism
chemical_list: D054795:Incretins; D052216:Glucagon-Like Peptide 1