Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Abstract

Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weightindependent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic b-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides (for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment. Keywords: diabetes; gastric bypass; bariatric surgery; ghrelin; GLP-1 Bariatric operations traditionally have been thought to cause weight loss through gastric restriction and/or intestinal malabsorption. Restrictive operations such as adjustable gastric banding (AGB) create a small pouch in the proximal stomach to reduce functional gastric capacity and retard gastric emptying. Malabsorptive procedures such as biliopancreatic diversion (BPD) leave much of the stomach intact but divert ingested food from the stomach to the ileum; thus, only a small segment of the distal bowel can absorb nutrients. The typical proximal Roux-en-Y gastric bypass (RYGB) creates gastric restriction and also causes food to bypass most of the stomach and a short segment of the proximal intestine, primarily the duodenum, leaving enough intact small bowel in digestive continuity to avoid clinically significant malabsorption. RYGB causes weight loss through gastric restriction and additional mechanisms involving changes in gut hormones and other processes under active investigation. 1-14 RYGB and BPD produce the highest and most rapid rates of remission of type 2 diabetes mellitus (T2DM). Remission of diabetes after RYGBAlthough bariatric surgery was designed to facilitate weight loss, anecdotal reports of rapid postoperative remission of T2DM emerged as early as the 1970s. In 1995, Pories et al. 4 reported long term results from 608 severely obese patients who underwent gastric bypass, with a 93% follow-up rate ov...

Endocrine effects of duodenal–jejunal exclusion in obese patients with type 2 diabetes mellitus

“…This operation combines the restrictive element (creation of a small stomach pouch) with its connection to the medium part of jejunum, so that the food bypasses the distal stomach, duodenum and proximal jejunum (the malabsorptive component). Numerous studies have documented multiple positive metabolic effects of gastric bypass, in particular the improvement in glucose control or even a complete diabetes remission that occur early after operation and are at least partially independent of weight loss (Cummings 2009). Although gastric bypass is an effective and durable approach to target both obesity and T2DM, it is still a major surgical procedure with all its limitations including the risk of perioperative or postoperative complications and also its irreversibility.…”

Evaluation of weight loss and metabolic profile of obese patients with type 2 diabetes mellitus (dm2) versus non-dm2 subjects, one and three years after bariatric surgery

“…The Rouxen-Y gastric-bypass (RYGB) is the most commonly employed technique being predominantly restrictive 11 . Bariatric surgery is a highly efficient means of controlling illnesses related to obesity, especially type 2 diabetes mellitus (DM2), which improves before significant weight loss 6,14 . This fact can be explained not only because of the surgery's restrictive effect and a certain level of malabsortion, but also due to the control of the patient's appetite and enteric celerity caused by incretins (GIP and GLP-1), whose release and effect is considerably augmented in DM2 patients submitted to bariatric surgery 7 .…”

Bariatric surgery in patients with Type 2 diabetes: benefits, risks, indications and perspectives

“…Weightindependent antidiabetic effects with RYGB are evident from the rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homoeostasis after RYGB than after equivalent weight loss by other means and the occasional development of very-late-onset pancreatic β-cell hyperfunctioning. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including: enhanced nutrient stimulation of L-cell peptides [for example, glucagon-like peptide-1 (GLP-1)] from the lower intestine ('hindgut hypothesis'); the intriguing, but as yet uncharacterized, phenomena related to exclusion of the upper intestine from contact with ingested nutrients ('foregut hypothesis'); compromised ghrelin secretion; and most likely other effects that have yet to be identified [30,35,36]. Indeed, a role for glucagon or gut-derived glucagonotropic signalling as putative diabetogenic signals from the foregut has been recently proposed [37].…”

“…Indeed, a role for glucagon or gut-derived glucagonotropic signalling as putative diabetogenic signals from the foregut has been recently proposed [37]. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help in the optimalization of surgical design (see Perspectives below) and may also reveal novel pharmaceutical targets for antidiabetes drug treatments [36].…”