Series
Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery

https://doi.org/10.1016/S2213-8587(13)70218-3Get rights and content

Summary

Bariatric surgery is the most effective treatment for obesity and also greatly improves glycaemic control, often within days after surgery, independently of weight loss. Laparoscopic adjustable gastric banding (LAGB) was designed as a purely restrictive procedure, whereas vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) induce changes in appetite through regulation of gut hormones, resulting in decreased hunger and increased satiation. Thus, VSG and RYBG more frequently result in remission of type 2 diabetes than does LAGB. With all three of these procedures, remission of diabetes is associated with early increases in insulin sensitivity in the liver and later in peripheral tissues; VSG and RYBG are also associated with improved insulin secretion and an exaggerated postprandial rise in glucagon-like peptide 1. The vagal pathway could have a role in the neurohumoral regulatory pathways that control appetite and glucose metabolism after bariatric surgery. Recent research suggests that changes in bile acid concentrations in the blood and altered intestinal microbiota might contribute to metabolic changes after surgery, but the mechanisms are unclear. In this Series paper, we explore the possible mechanisms underlying the effects on glucose metabolism and bodyweight of LAGB, VSG, and RYGB surgery. Elucidation of these mechanisms is providing knowledge about bodyweight regulation and the pathophysiology of type 2 diabetes, and could help to identify new drug targets and improved surgical techniques.

Introduction

The increasing prevalence of obesity has generated a secondary epidemic of metabolic syndrome—ie, abdominal obesity with increased risk of type 2 diabetes and cardiovascular diseases.1, 2 Additional metabolic comorbidities include polycystic ovary syndrome and non-alcoholic steatohepatitis. Obesity is also associated with obstructive sleep apnoea and several cancers.1 Abdominal obesity and ectopic fat deposits in the liver, pancreas, and skeletal and heart muscle can lead to insulin resistance.2 Obesity can also cause suppression of adiponectin and increases in concentrations of fatty acids, proinflammatory cytokines (including tumour necrosis factor [TNF] and interleukin 6), and fibrinogen—all of which contribute to insulin resistance, pancreatic β-cell dysfunction, and low-grade inflammation in the vascular system, with increased C-reactive protein and plasma activator inhibitor 1.2

Treatment of obesity with lifestyle changes focused on weight loss and increased physical activity can cause patients to lose 5–10% of their bodyweight, but most will start to regain weight after 3–9 months, and after 1–5 years about 90% will have returned to their original weight, or might even weigh more than before the intervention.3 Addition of anti-obesity drugs to lifestyle changes can add a further weight loss of 2–8 kg.3 By contrast, bariatric surgery effectively treats obesity and its comorbidities through radical effects on energy intake and glucose metabolism. Notably, in some cases, improvement in glycaemic control after bariatric surgery in people with type 2 diabetes occurs within days of surgery and before any weight loss, and the effect is also seen in mildly overweight patients.4, 5 The International Diabetes Federation advocates bariatric surgery for the treatment of subgroups of patients with type 2 diabetes.6 Roughly 350 000 bariatric operations are done worldwide every year.5 Laparoscopic Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure, followed by vertical sleeve gastrectomy (VSG) and laparoscopic adjustable gastric banding (LAGB), with VSG becoming increasingly popular.7 Biliopancreatic diversion (BPD) with duodenal switch is used less often than the other procedures.7

In this Series paper, we explore the possible mechanisms underlying the metabolic effects of bariatric surgery, with a focus on weight loss and resolution of type 2 diabetes. We also discuss less invasive surgical procedures and other therapeutic strategies for obesity and type 2 diabetes inspired by bariatric surgery that might be used increasingly in the future. We focus mainly on studies of LAGB, RYGB, and VSG in human beings.

Section snippets

Effects of bariatric surgery on bodyweight and type 2 diabetes

The large range of bariatric procedures and their development have been reviewed elsewhere.8 Briefly, the operations have traditionally been divided into restrictive procedures, including LAGB and VSG, and those that induce bypass of one or more segments of the gastrointestinal tract, such as RYGB (figure 1).

Bariatric surgery produces major and durable weight loss. In Buchwald and colleagues' meta-analysis,9 weight loss (expressed as percentage of excess weight) averaged 47% after LAGB, 62%

Gastric restriction

Physicians initially speculated that weight loss after bariatric surgery was due to mechanical restriction and, for procedures that involve bypass, malabsorption of foods.8 Subsequently, the focus of research has shifted towards the metabolic effects of the surgeries. Some of the most important mechanisms underlying weight loss and remission of type 2 diabetes after LAGB, VSG, and RYGB are summarised in the table.

LAGB has traditionally been regarded as a restrictive procedure, but Burton and

Weight loss

LAGB, RYGB, and VSG seem to induce weight loss by partly overlapping mechanisms. None of these procedures should be regarded as restrictive, including LAGB. Optimally adjusted LAGB only briefly delays the passage of semisolid food through the band, and the gastric and intestinal transit of food is normal.21 As discussed, distension stimuli from the small pouch could be transmitted via vagus afferents to areas of the central nervous system implicated in satiety.22 No hormonal changes account for

Future prospects

Less invasive treatments that mimic the effects of bariatric surgery are of interest for the treatment of obesity and type 2 diabetes. However, so far, the positive effects of surgery have not been replicated by any medical treatment. Targeting two or more anorexigenic pathways might be necessary to achieve substantial weight loss. The GLP-1 receptor agonists are very effective for the treatment of type 2 diabetes, inducing a reduction in HbA1c greater than oral antidiabetic drugs, together

Conclusions

Obesity and type 2 diabetes are closely linked health problems. No existing dietary or exercise regimen can restore and sustain a healthy bodyweight for an extended period in most obese patients. The only available intervention with curative potential is bariatric surgery, which is invasive, often irreversible, and has associated risk. Such surgery cannot be delivered on a mass scale and is currently reserved for severely obese individuals.

Bariatric surgery was originally designed for weight

Search strategy and selection criteria

We searched PubMed for reports published in English up to Aug 1, 2013. The search terms “bariatric surgery”, “gastric bypass”, “sleeve gastrectomy”, “gastric banding”, “biliopancreatic diversion” were used alone and in combination with “diabetes mellitus”, “β-cell function”, “insulin resistance”, “weight loss”, “appetite”, “energy expenditure”, “caloric restriction”, “bile acids”, “microbiota”, “gene polymorphism”, and “future treatment”. We also manually searched the relevant scientific

References (128)

  • J Korner et al.

    Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding

    Surg Obes Relat Dis

    (2007)
  • WJ Lee et al.

    Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy

    Surg Obes Relat Dis

    (2011)
  • BA Whitson et al.

    Adipokine response in diabetics and nondiabetics following the Roux-en-Y gastric bypass: a preliminary study

    J Surg Res

    (2007)
  • AE Field et al.

    Impact of overweight on the risk of developing common chronic diseases during a 10-year period

    Arch Intern Med

    (2001)
  • G Derosa et al.

    Anti-obesity drugs: a review about their effects and their safety

    Expert Opin Drug Saf

    (2012)
  • C Dirksen et al.

    Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

    Diabetologia

    (2012)
  • JB Dixon et al.

    Bariatric surgery: an IDF statement for obese type 2 diabetes

    Diabet Med

    (2011)
  • H Buchwald et al.

    Metabolic/bariatric surgery worldwide 2011

    Obes Surg

    (2013)
  • H Ashrafian et al.

    Metabolic surgery: an evolution through bariatric animal models

    Obes Rev

    (2010)
  • H Buchwald et al.

    Bariatric surgery: a systematic review and meta-analysis

    JAMA

    (2004)
  • A Keidar et al.

    Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial

    Diabetologia

    (2013)
  • L Sjöström et al.

    Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery

    N Engl J Med

    (2004)
  • JB Buse et al.

    How do we define cure of diabetes?

    Diabetes Care

    (2009)
  • DJ Pournaras et al.

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

    Br J Surg

    (2012)
  • DE Arterburn et al.

    A multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypass

    Obes Surg

    (2013)
  • JB Dixon et al.

    Predicting the glycemic response to gastric bypass surgery in patients with type 2 diabetes

    Diabetes Care

    (2013)
  • JB Dixon et al.

    Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial

    JAMA

    (2008)
  • PR Schauer et al.

    Bariatric surgery versus intensive medical therapy in obese patients with diabetes

    N Engl J Med

    (2012)
  • SR Kashyap et al.

    Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment

    Diabetes Care

    (2013)
  • G Mingrone et al.

    Bariatric surgery versus conventional medical therapy for type 2 diabetes

    N Engl J Med

    (2012)
  • S Ikramuddin et al.

    Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial

    JAMA

    (2013)
  • PR Burton et al.

    The mechanism of weight loss with laparoscopic adjustable gastric banding: induction of satiety not restriction

    Int J Obes (Lond)

    (2011)
  • J Kampe et al.

    Neural and humoral changes associated with the adjustable gastric band: insights from a rodent model

    Int J Obes (Lond)

    (2012)
  • JA Tadross et al.

    The mechanisms of weight loss after bariatric surgery

    Int J Obes (Lond)

    (2009)
  • Y Falken et al.

    Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides

    J Clin Endocrinol Metab

    (2011)
  • NB Jorgensen et al.

    The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

    Diabetes

    (2013)
  • C Dirksen et al.

    Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass

    Neurogastroenterol Motil

    (2013)
  • H Bernstine et al.

    Gastric emptying is not affected by sleeve gastrectomy—scintigraphic evaluation of gastric emptying after sleeve gastrectomy without removal of the gastric antrum

    Obes Surg

    (2009)
  • P Bjorklund et al.

    Is the Roux limb a determinant for meal size after gastric bypass surgery?

    Obes Surg

    (2010)
  • F Rodieux et al.

    Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release

    Obesity (Silver Spring)

    (2008)
  • D Bradley et al.

    Gastric bypass and banding equally improve insulin sensitivity and β cell function

    J Clin Invest

    (2012)
  • SH Jacobsen et al.

    Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

    Diabetologia

    (2013)
  • M Nannipieri et al.

    Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones

    J Clin Endocrinol Metab

    (2013)
  • R Peterli et al.

    Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial

    Obes Surg

    (2012)
  • WO Griffen et al.

    A prospective comparison of gastric and jejunoileal bypass procedures for morbid obesity

    Ann Surg

    (1977)
  • A Schwartz et al.

    Relative changes in resting energy expenditure during weight loss: a systematic review

    Obes Rev

    (2010)
  • G Benedetti et al.

    Body composition and energy expenditure after weight loss following bariatric surgery

    J Am Coll Nutr

    (2000)
  • F Carrasco et al.

    Changes in resting energy expenditure and body composition after weight loss following Roux-en-Y gastric bypass

    Obes Surg

    (2007)
  • M Werling et al.

    Increased postprandial energy expenditure may explain superior long term weight loss after Roux-en-Y gastric bypass compared to vertical banded gastroplasty

    PLoS One

    (2013)
  • M Bueter et al.

    Gastric bypass increases energy expenditure in rats

    Gastroenterology

    (2010)
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