Immediate Diabetes Resolution after GB Surgery

Abstract & Commentary

By Nicole R. Basa, MD, Clinical Instructor, Department of Surgery, UCLA Division of Minimally Invasive and Bariatric Surgery. Dr. Basa reports no financial relationships relevant to this field of study.

Synopsis: Bypassing the duodenum and proximal jejunum causes improvement in blood glucose control in patients with Type 2 Diabetes as demonstrated by a surgical diabetic rat model.

Source: Rubino F, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741-749.

Background: Most patients with Type 2 Diabetes who undergo Roux-en-Y Gastric Bypass (GB) surgery experience immediate resolution of their diabetes. Immediately, in the postoperative period, blood sugars improve prior to any weight loss changes. The rearranged intestine appears to play a role in the improved glucose homeostasis. There are 2 working hypotheses to why this occurs: 1) enhanced delivery of nutrients to the distal intestine, with increased secretion of hindgut signals to improve glucose control or 2) excluding the proximal intestine to change glucose signaling.

Methods: Goto-Kakizaki (GK) type 2 diabetic rats underwent 3 different types of operations: 1) Duodenal-Jejunal Bypass (DJB), 2) stomach-preserving RYGB, which excludes the proximal intestine, and 3) a Gastrojejunostomy (GJ), whereby a loop of jejunum is connected to the stomach to create a shortcut to the hindgut without a bypass of any intestine.

Results: DJB-treated rats had better oral glucose tolerance compared with controls. GJ did not affect glucose control, but exclusion of the duodenum in reoperated rats did improve glucose control. Restoration of duodenal nutrient passage in DJB rats reestablished poor glucose control.

Conclusions: This study demonstrates that the bypass of the proximal small intestine improves glucose homeostasis, independent of food intake, body weight, and malabsorption or nutrient delivery to the hindgut.

Commentary

This study demonstrates how surgical treatment for morbid obesity affects glucose homeostasis. Clinically, blood sugars of patients with diabetes type 2 show dramatic improvement soon after gastric bypass surgery. The improvement of diabetes occurs within the immediate postoperative period. It is not due to the long-term effects of decreased food intake or weight loss. These long-term findings improve other comorbidities due to morbid obesity, such as hypertension, sleep apnea, gastroesophageal reflux disease, and degenerative joint disease.

By performing surgery in diabetic rats, different types of operations were used to assess if improved glucose control was due to the absence of nutrients passing the proximal small bowel vs accelerated nutrients passing to the hindgut. Sham-operated, pair-fed animals, as well as unoperated, pair-fed animals were used as controls. This study nicely demonstrated that the diabetic rats that had a proximal intestinal bypass had a marked improvement in glucose tolerance. The rats with a loop gastrojejunostomy were noted to have no benefit in glucose homeostasis. These same rats were operated on again 4 weeks later to divide the connection between the stomach and the duodenum. The reoperated rats showed improved glucose control due to the presumed lack of nutrient flow within the proximal small bowel. These results corroborate Rubino and Marescaux's earlier work, which demonstrated that DJB ameliorates type 2 diabetes in diabetic rats very rapidly and more effectively than by restricting food intake in matched nonoperated animals.1

Several other clinical studies showed that excluding the duodenum improves glucose control in diabetic patients. Early data from 1955 showed that diabetic patients who required a subtotal gastrectomy and a bypass of their proximal duodenum and jejunum were noted to have markedly improved blood glucose levels.2

The dramatic finding that by bypassing the proximal small intestine Type 2 diabetes can be cured, is impressive. This finding has sparked research into finding out the hormone that is secreted in the proximal small intestine which is responsible for improved glucose control. If this hormone is found, millions of people who suffer from Type 2 diabetes may benefit. If a hormone is not found, patients who suffer from type 2 diabetes, who have a BMI less than 35, may benefit from a Roux-en-Y GB, or some form of this operation which bypasses the proximal small bowel.

References

1. Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: A new perspective for an old disease. Ann Surg. 2004;239:1-11.

2. Friedman NM, et al. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg Gynecol Obstet. 1955;100:201-204.