Gastrointestinal surgery as treatment for type 2 diabetes.

Weill Cornell Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 10065, USA.

PURPOSE OF REVIEW: As the incidence of type 2 diabetes continues to rise worldwide at epidemic proportions, endeavors to find more effective therapies increase. Gastrointestinal bypass surgery is now gaining awareness as a potential effective and long-term treatment.

RECENT FINDINGS: There is now a substantial body of evidence supporting the efficacy of gastrointestinal surgery in controlling type 2 diabetes. This is well documented in several studies of obese diabetic patients undergoing gastrointestinal bypass procedures. Additionally, smaller studies and case reports also demonstrate the efficacy of gastrointestinal bypass surgery in nonobese diabetic patients. The pathophysiologic basis of the improvement in diabetes after gastrointestinal bypass surgery is still unclear; however, the dominant hypotheses involve changes in hormone signaling from the small bowel.

SUMMARY: The implications of 'diabetes surgery' are vast, and could dramatically change the face of diabetes as we know it today. In clinical practice surgery could represent an alternative for the treatment of diabetes. On a broader perspective, surgery may facilitate research aimed at understanding the etiology of the disease.

PMID: 18316951 [PubMed - indexed for MEDLINE

Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis.

Department of Surgery, Catholic University of Rome, Rome, Italy. frr2007@med.cornell.edu

Type 2 diabetes, which accounts for 90-95% of all cases of diabetes, is a growing epidemic that places a severe burden on health care systems, especially in developing countries. Because of both the scale of the problem and the current epidemic growth of diabetes, it is a priority to find new approaches to better understand and treat this disease. Gastrointestinal surgery may provide new opportunities in the fight against diabetes. Conventional gastrointestinal operations for morbid obesity have been shown to dramatically improve type 2 diabetes, resulting in normal blood glucose and glycosylated hemoglobin levels, with discontinuation of all diabetes-related medications. Return to euglycemia and normal insulin levels are observed within days after surgery, suggesting that weight loss alone cannot entirely explain why surgery improves diabetes. Recent experimental studies point toward the rearrangement of gastrointestinal anatomy as a primary mediator of the surgical control of diabetes, suggesting a role of the small bowel in the pathophysiology of the disease. This article presents available evidence in support of the hypothesis that type 2 diabetes may be an operable disease characterized by a component of intestinal dysfunction.

PMID: 18227499 [PubMed - indexed for MEDLINE]

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

IRCAD-European Institute of Telesurgery, University Louis Pasteur, Strasbourg, France. f.rubino@lycos.com

SUMMARY BACKGROUND DATA: Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. METHODS: Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. RESULTS: There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. CONCLUSIONS: This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

PMID: 17060767 [PubMed - indexed for MEDLINE]