Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss

Science Translational Medicine  27 Apr 2011:
Vol. 3, Issue 80, pp. 80re2
DOI: 10.1126/scitranslmed.3002043

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Dissecting the Quick Fix

In the Wizard of Oz, when Dorothy encounters a split in the yellow brick road, the Scarecrow assures her that all paths lead to the land of Oz. We’ve witnessed the perils Dorothy met along the path she chose; however, we don’t know what she would have encountered had she followed another route to Oz. Similarly, obese patients with type 2 diabetes can take one of two paths to weight loss—dietary intervention or gastric bypass surgery (GBP). Although the end result—weight loss—is the same, the metabolic shifts that occur en route appear to differ. Now, Laferrère et al. show that in patients with equivalent weight loss, those who underwent GBP displayed a larger decrease in certain circulating amino acids than did subjects who pursued the dietary intervention path. This difference may help to explain why patients who opted for the surgical intervention boasted better improvement in glucose homeostasis—including enhanced insulin sensitivity—than did those who lost weight by controlling their dietary intake.

Obese patients with type 2 diabetes strive to lose weight for reasons more momentous than an approaching swimsuit season. Weight loss can improve the body’s ability to metabolize glucose and thus stems the serious complications of diabetes. Patients often can reduce or forgo their diabetes medications. However, in such patients, glycemic control is improved to a greater extent within days after GBP—before weight loss occurs—than after diet-induced shedding of pounds and inches. Precisely why remains a mystery, but research in animal models has revealed that higher-than-normal blood concentrations of branched-chain amino acids (BCAAs) and their metabolites play a role in the loss of insulin sensitivity. Furthermore, recent studies in human patients show a robust positive correlation between insulin resistance and blood levels of BCAAs and their by-products. Finally, obese people have higher circulating concentrations of these amino acids compared to their lean counterparts; the same goes for individuals with versus without diabetes. These observations imply that the rapid reversal of diabetes symptoms in GBP patients may have something to do with BCAA metabolism.

Here, the authors measured circulating amounts of a variety of amino acids and acylcarnitines—some of which are produced primarily from BCAA metabolism—to characterize the differential metabolic responses to weight loss induced by GBP versus dietary intervention in obese type 2 diabetes patients. Circulating concentrations of total amino acids, BCAAs, and BCAA metabolites all decreased significantly after GBP but not after dietary intervention, despite equivalent weight loss. These findings were consistent in two patient cohorts, one from the New York Obesity Nutrition Research Center and one from Duke University; in the latter group, the effects were shown to persist for months. These data support the notion that the surgical intervention promoted enhanced BCAA metabolism by mechanisms separate from weight loss and suggest that changes in circulating amino acids pave the road to the correction of glycemic control observed after GBP.


  • Present address: Division of Pediatric Endocrinology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada T6G 2J3.

  • Citation: B. Laferrère, D. Reilly, S. Arias, N. Swerdlow, P. Gorroochurn, B. Bawa, M. Bose, J. Teixeira, R. D. Stevens, B. R. Wenner, J. R. Bain, M. J. Muehlbauer, A. Haqq, L. Lien, S. H. Shah, L. P. Svetkey, C. B. Newgard, Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss. Sci. Transl. Med. 3, 80re2 (2011).

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