The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes

Rubino, Francesco; Forgione, Antonello; Cummings, David E.; Vix, Michel; Gnuli, Donatella; Mingrone, Geltrude; Castagneto, Marco; Marescaux, Jacques

doi:10.1097/01.sla.0000224726.61448.1b

Cited by 810 publications

(597 citation statements)

References 30 publications

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“…13 A variation of DJB, in which ingested food passes from the stomach into both the proximal jejunum and the proximal duodenum, had no impact on glycemia. GotoKakizaki rats subjected to DJB with duodenal exclusion followed by DJB without duodenal exclusion, or vice versa, experienced reversible remission and reconstitution of T2DM.…”

Section: The Upper Intestinal Hypothesismentioning

confidence: 94%

“…[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%

“…13,19,[46][47][48] Thus, although these interventions seem only to re-route the flow of food through the GI tract after meals, they exert salutary effects on glycemia that persist between meals.…”

Section: The Upper Intestinal Hypothesismentioning

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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confidence: 99%

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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: The Upper Intestinal Hypothesismentioning

confidence: 94%

“…[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: The Upper Intestinal Hypothesismentioning

confidence: 99%

mentioning

confidence: 99%

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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“…Experiments in a non-obese type 2 diabetes rodent model demonstrated that surgical control of diabetes by gastrointestinal bypass is the direct effect of the anatomical rearrangement of the small bowel, independently of weight loss [2]. Surgical control of diabetes may thus be potentially obtained also in patients who do not meet current criteria for bariatric surgery (BMI >40 kg/m 2 or BMI >35 kg/m 2 with high-risk comorbid conditions).…”

Section: Introductionmentioning

confidence: 99%

The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2

et al. 2009

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Aims/hypothesis To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI <35 kg/m 2 . Methods OGTTs were performed and anthropometric data were compared between five diabetes patients (BMI 27-33 kg/m 2 ) following BPD and seven diabetes patients after a low-energy diet. Insulin secretion was computed by C-peptide deconvolution. A euglycaemic-hyperinsulinaemic clamp was performed only in the BPD group and the M value measured. Results One month after BPD, fasting and 2 h post-OGTT glycaemia decreased from 15.22±3.22 to 6.22± 0.51 mmol/l (p=0.043), while insulin sensitivity increased significantly. No significant changes were observed in the low-energy diet group. Insulin secretion did not differ significantly after either intervention. Diabetes amelioration (change in HbA 1c level) was observed up to 18 months after BPD without pharmacological therapy. Conclusions/interpretation BPD can achieve adequate control of type 2 diabetes also in patients with BMI <35 kg/m 2 . The rapid postoperative remission of diabetes is primarily related to an improvement in insulin sensitivity.

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Factors Associated With Weight Loss After Gastric Bypass

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Mulligan³

et al. 2008

Arch Surg

153

101

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The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes

Cited by 810 publications

References 30 publications

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2

Factors Associated With Weight Loss After Gastric Bypass

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