Gastrointestinal Surgery as a Treatment for Diabetes

Cummings, David E.; Flum, David R.

doi:10.1001/jama.299.3.341

Cited by 43 publications

(28 citation statements)

References 30 publications

(21 reference statements)

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“…22 In contrast, purely gastric-restrictive operations such as AGBFwhich, similar to RYGB, involve peri-operative restriction of energy intake followed by longterm weight lossFameliorate diabetes only after substantial weight loss is achieved. 6,23 One study, in which glucose homeostasis was examined very soon after RYGB, reported that insulin sensitivity (estimated by homeostatic model assessment and the AUC (area-under-the-curve) glucose after an intravenous glucose tolerance testing) was significantly increased at only 6 days following surgery, before any meaningful weight loss had occurred. 22 In that study, the improvement in glucose tolerance appeared to result from reduced basal glucose levels before the i.v.…”

Section: Mechanisms Of Diabetes Improvement Following Bariatric Surgerymentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14] None of these theories is necessarily exclusive of these others, and any or all them may be operational to some degree.…”

Section: Theories Regarding Weight-independent Anti-diabetic Mechanismentioning

confidence: 99%

“…In a randomized trial by Dixon et al of AGB vs best medical care to treat T2DM, none of the surgical patients had experienced remission of diabetes by 6 months after the operation, even though the disease ultimately did remit by 2 years in 73% of these individuals (who had very mild T2DM at baseline). 6,23 In marked contrast, most patients with T2DM who undergo RYGB experience full remission of their disease within several days to a few weeks after the operation (vide supra). 5,22 Patients undergoing many types of general surgery are subjected to immediate perioperative restriction of energy intake.…”

Section: Theories Regarding Weight-independent Anti-diabetic Mechanismentioning

confidence: 99%

“…RYGB causes weight loss through gastric restriction and additional mechanisms involving changes in gut hormones and other processes under active investigation. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] RYGB and BPD produce the highest and most rapid rates of remission of type 2 diabetes mellitus (T2DM).…”

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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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...

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Section: Mechanisms Of Diabetes Improvement Following Bariatric Surgerymentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14] None of these theories is necessarily exclusive of these others, and any or all them may be operational to some degree.…”

Section: Theories Regarding Weight-independent Anti-diabetic Mechanismentioning

confidence: 99%

Section: Theories Regarding Weight-independent Anti-diabetic Mechanismentioning

confidence: 99%

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confidence: 99%

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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“…Here, the surgical patients had a 5 times higher remission rate for diabetes compared with medical controls, and weight loss was the principal predictor of diabetes remission. 31,57 The mechanisms for weight loss after metabolic surgery are muiltifactorial 11,12 and include the modulation of gut hormones that lead to alterations in appetite, hunger, dietary feeding behavior, and, more recently, taste modulation in addition to alterations in metabolic rate and resting energy expenditure. 11,58,59 Although, traditionally, surgery was considered to achieve weight loss through the malabsorption of food and restriction of stomach size, there is some discrepancy supporting the effects of stomach-pouch size or calorific malabsorption other than for a minority of procedures (such as the biliopancreatic diversion).…”

Section: Decreased Obesity Through Weight Lossmentioning

confidence: 99%

Metabolic surgery and cancer

Ashrafian

Ahmed

Rowland

et al. 2010

Cancer

136

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The worldwide epidemic of obesity and the global incidence of cancer are both increasing. There is now epidemiological evidence to support a correlation between obesity, weight gain, and some cancers. Metabolic or bariatric surgery can provide sustained weight loss and reduced obesity-related mortality. These procedures can also improve the metabolic profile to decrease cardiovascular risk and resolve diabetes in morbidly obese patients. The operations offer several physiological steps, the so-called BRAVE effects: 1) bile flow alteration, 2) reduction of gastric size, 3) anatomical gut rearrangement and altered flow of nutrients, 4) vagal manipulation and 5) enteric gut hormone modulation. Metabolic operations are also associated with a significant reduction of cancer incidence and mortality. The cancer-protective role of metabolic surgery is strongest for female obesity-related tumors; however, the underlying mechanisms may involve both weight-dependent and weight-independent effects. These include the improvement of insulin resistance with attenuation of the metabolic syndrome as well as decreased oxidative stress and inflammation in addition to the beneficial modulation of sex steroids, gut hormones, cellular energetics, immune system, and adipokines. Elucidating the precise metabolic mechanisms of cancer prevention by metabolic surgery can increase our understanding of how obesity, diabetes, and metabolic syndrome are associated with cancer. It may also offer novel treatment strategies in the management of tumor generation and growth. Cancer 2011;117:1788-99. V C 2010 American Cancer Society.KEYWORDS: metabolic surgery, bariatric surgery, cancer, oncology.The worldwide epidemic of obesity and the global incidence of cancer are both increasing. According to the World Health Organization (WHO), obesity is rising by 30 million cases per year, 1 whereas the overall number of new cancer cases will increase by 300,000 cases per year.2 Both obesity and cancer contribute to increased worldwide mortality and healthcare costs. They are now both recognized as global healthcare concerns and have been the subject of worldwide calls to action. 3,4Several treatment strategies have been developed to decrease obesity; these include prevention, lifestyle, behavioral modification, and pharmacotherapy. The weight-loss effects of these strategies have only been marginally successful, 5 and, therefore, a surgical solution has been developed to provide consistent weight loss in severely obese patients. The operations initially titled ''bariatric procedures'' have demonstrated long-term weight loss at more than 15 years after surgery 6,7 ; however in addition, they achieve pronounced metabolic effects including diabetes resolution in the majority of morbidly obese patients. [8][9][10] As a result, these procedures are now considered as ''metabolic'' operations. 10-14The epidemiological association between obesity rates and cancer rates has come under increased scrutiny as there is now evidence to establish obesity as a significant...

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