Metabolic changes within the Roux limb, which is generated during Roux-en-Y gastric bypass (RYGB) surgery, underlie the remission of type 2 diabetes mellitus (T2DM) observed after this bariatric procedure, suggests a US research group.

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The beneficial effects of bariatric surgery on body weight are widely acknowledged. Importantly, other beneficial effects include a drastic reduction in the comorbidities of obesity, such as hyperlipidaemia, hypertension and T2DM. This finding has led some clinicians to advocate a renaming of these procedures as 'metabolic surgery'.

Strikingly, improvements in glucose homeostasis after RYGB are seen well before any significant weight loss has occurred. This fact has fueled the search for the physiological mechanisms underlying the metabolic changes observed after bariatric surgery, in the hopes that new, direct treatment targets will preclude the need for surgical intervention. To date, several possible explanations have been put forward, for example, altered composition of the gut microbiota or changes in the levels of circulating gastrointestinal hormones that affect the central neurocircuits regulating food intake and energy expenditure.

Now, Saeidi et al. show that RYGB surgery induces changes in intestinal glucose metabolism in diet-induced obese rats and in two nonobese, diabetic rodent models with impaired insulin secretion. This “reprogramming”, as the authors call it, converts the intestine into a major tissue for glucose disposal, as determined by 18F-FDG-PET–CT, and contributes substantially to the improved whole-body glycaemic control that occurs after RYGB, independently of weight loss.

Using a rat model in which a loop of the jejunum was transected and transposed between the oesophagus and the stomach but no other anatomic alterations of the RYGB procedure had been performed, the researchers could confirm that intestinal remodelling and reprogramming of intestinal glucose metabolism were triggered by exposure of the Roux limb to undigested nutrients.

Taken together, these findings implicate alterations in the gut itself in the remission of T2DM after bariatric surgery, as opposed to changes in the way the gut signals to other parts of the body. The investigators hope that exploiting the changes in intestinal metabolism after RYGB will help to “bypass the bypass, that is, to replace the gastric bypass by equally effective, but less invasive, treatments”.